EAU Guidelines On Urolithiasis 2023

EAU Guidelines on
Urolithiasis
A. Skolarikos (Chair), H. Jung, A. Neisius,
A. Petřík, B. Somani, T. Tailly,
G. Gambaro (Consultant nephrologist)
Guidelines Associates: N.F. Davis, R. Geraghty,
R. Lombardo, L. Tzelves
Guidelines Office: R. Shepherd
© European Association of Urology 2023

TABLE OF CONTENTS PAGE
1. INTRODUCTION 6
1.1 Aims and scope 6
1.2 Panel composition 6
1.3 Available publications 6
1.4 Publication history and summary of changes 6
1.4.1 Publication history 6
1.4.2 Summary of changes 6
2. METHODS 6
2.1 Data identification 6
2.2 Review 7
2.3 Future goals 7
3. GUIDELINES 7
3.1 Prevalence, aetiology, risk of recurrence 7
3.1.1 Introduction 7
3.1.2 Stone composition 8
3.1.3 Risk groups for stone formation 8
3.2 Classification of stones 10
3.2.1 Stone size 11
3.2.2 Stone location 11
3.2.3 X-ray characteristics 11
3.3 Diagnostic evaluation 11
3.3.1 Diagnostic imaging 11
3.3.1.1 Evaluation of patients with acute flank pain/suspected ureteral stones 11
3.3.2 Diagnostics - metabolism-related 12
3.3.2.1 Basic laboratory analysis - non-emergency urolithiasis patients 12
3.3.2.2 Analysis of stone composition 12
3.3.2.3 Recommendations for laboratory examinations and stone analysis 12
3.3.3 Diagnosis in special groups and conditions 13
3.3.3.1 Diagnostic imaging during pregnancy 13
3.3.3.2 Diagnostic imaging in children 13
3.3.3.2.1 Summary of evidence and recommendations for
diagnostic imaging in children 14
3.4 Disease Management 14
3.4.1 Renal colic 14
3.4.1.1 Summary of evidence and recommendations for the management of
renal colic 15
3.4.2 Management of sepsis and/or anuria in obstructed kidney 15
sepsis and anuria 16
3.4.3 Medical expulsive therapy 16
3.4.3.1 Summary of evidence and recommendations for MET 16
3.4.4 Chemolysis 17
3.4.4.1 Summary of evidence and recommendations for chemolysis 17
3.4.5 Extracorporeal shock wave lithotripsy (ESWL) 17
3.4.5.1 Summary of evidence and recommendations for SWL 19
3.4.6 Ureteroscopy (retrograde and antegrade) 19
3.4.6.1 Summary of evidence and recommendations for retrograde URS,
RIRS and antegrade ureteroscopy 21
3.4.7 Percutaneous nephrolithotomy 21
3.4.7.1 Summary of evidence and recommendations for endourology
techniques for renal stone removal 23
3.4.8 General recommendations and precautions for stone removal 24
3.4.8.1 Antibiotic therapy 24
3.4.8.2 Antithrombotic therapy and stone treatment 24
3.4.8.2.1 Summary of evidence and recommendations for
antithrombotic therapy and stone treatment 26
2 UROLITHIASIS - LIMITED UPDATE MARCH 2023

3.4.8.3 Obesity 26
3.4.8.4 Stone composition 26
3.4.8.5 Contraindications of procedures 26
3.4.9 Specific stone management of ureteral stones 27
3.4.9.1 Conservative treatment/observation 27
3.4.9.2 Pharmacological treatment, medical expulsive therapy 27
3.4.9.3 Indications for active removal of ureteral stones 27
3.4.9.4 Selection of procedure for active removal of ureteral stones 27
3.4.9.4.1 Summary of evidence and recommendations for selection
of procedure for active removal of ureteral stones 28
3.4.10 Specific stone management of renal stones 29
3.4.10.1 Conservative treatment (observation) 29
3.4.10.2 Pharmacological treatment of renal stones 29
3.4.10.3 Indications for active stone removal of renal stones 29
3.4.10.4 Selection of procedure for active removal of renal stones 29
3.4.10.4.1 Stones in renal pelvis or upper/middle calyces 29
3.4.10.4.2 Stones in the lower renal pole 30
renal stones 30
3.4.11 Laparoscopy and open surgery 31
3.4.11.1 Recommendation for laparoscopy and open surgery 32
3.4.12 Steinstrasse 32
3.4.12.1 Summary of evidence and recommendations for steinstrasse 32
3.4.13 Management of patients with residual stones 32
3.4.13.1 Summary of evidence and recommendation for management of
patients with residual stones 33
3.4.14 Management of specific patient groups 33
3.4.14.1 Management of urinary stones and related problems during pregnancy 33
3.4.14.1.1 Summary of evidence and recommendation for the
management of urinary stones and related problems
during pregnancy 33
3.4.14.2 Management of stones in patients with urinary diversion 33
management of stones in patients with urinary diversion 34
3.4.14.3 Management of stones in patients with neurogenic bladder 34
management of stones in patients with neurogenic
bladder 35
3.4.14.4 Management of stones in patients with transplanted kidneys 35
management of stones in patients with transplanted
kidneys 35
3.4.14.5 Special problems in stone removal 36
3.4.15 Management of stones in children 36
3.4.15.1 Clinical presentation 36
3.4.15.2 Conservative management 36
3.4.15.3 Medical expulsive therapy in children 37
3.4.15.4 Extracorporeal shock wave lithotripsy 37
3.4.15.5 Endourological procedures 37
3.4.15.6 Open and laparoscopic/robot-assisted stone surgery 38
3.4.15.7 Special considerations on recurrence prevention 38
stones in children 38
3.5 Radiation exposure and protection during endourology 38
4. METABOLIC EVALUATION AND RECURRENCE PREVENTION 39

4.1 General metabolic considerations for patient work-up 39
4.1.1 Evaluation of patient risk 39
4.1.2 Urine sampling 40
4.1.3 Timing of specific metabolic work-up 41
UROLITHIASIS - LIMITED UPDATE MARCH 2023 3

4.1.4 Reference ranges of laboratory values 41
4.1.5 Risk indices and additional diagnostic tools 41
4.2 General considerations for recurrence prevention 42
4.2.1 Fluid intake 43
4.2.2 Diet 43
4.2.3 Lifestyle 44
4.2.4 Summary of evidence and recommendation for recurrence prevention 44
4.3 Stone-specific metabolic evaluation and pharmacological recurrence prevention 44
4.3.1 Introduction 44
4.4 Calcium oxalate stones 45
4.4.1 Diagnosis 45
4.4.2 Interpretation of results and aetiology 47
4.4.3 Specific treatment 49
4.4.4 Summary of evidence and recommendations for pharmacological treatments for
patients with specific abnormalities in urine composition (based on 24-hour urine
samples) 49
4.5 Calcium phosphate stones 49
4.5.1 Diagnosis 49
4.5.2 Interpretation of results and aetiology 49
4.5.3 Pharmacological therapy 50
4.5.4 Summary of evidence and recommendation for the management of calcium
phosphate Stones 50
4.6 Disorders and diseases related to calcium stones 50
4.6.1 Hyperparathyroidism 50
4.6.2 Granulomatous diseases 51
4.6.3 Primary hyperoxaluria 51
4.6.3.1 Summary of evidence and recommendation for the management of
primary hyperoxaluria 51
4.6.4 Enteric hyperoxaluria 51
4.6.5 Renal tubular acidosis 52
tubular acidosis 53
4.6.6 Nephrocalcinosis 53
4.6.6.1 Diagnosis 54
4.7 Uric acid and ammonium urate stones 54
4.7.1 Diagnosis 54
4.7.2 Interpretation of results 54
4.7.4 Summary of evidence and recommendations for the management of uric acid-
and ammonium urate stones 56
4.8 Struvite and infection stones 57
4.8.1 Diagnosis 57
4.8.2 Interpretation 57
4.9 Cystine stones 59
4.9.1 Diagnosis 59
4.9.2.1 Pharmacological treatment of cystine stones 59
4.9.3 Summary of evidence and recommendations for the management of cystine
stones 60
4.10 2,8-Dihydroxyandenine stones and xanthine stones 61
4.10.1 2,8-Dihydroxyadenine stones 61
4.10.2 Xanthine stones 61
4.10.3 Fluid intake and diet 61
4.11 Drug-induced stones 61
4.12 Matrix Stones 61
4.13 Unknown stone composition 61
4.13.1 Recommendations for investigations for the assessment of patients with stones
of unknown composition 62

5. FOLLOW-UP OF URINARY STONES 62
6. BLADDER STONES 66
6.1 Prevalence, aetiology, and risk factors of bladder stones 66
6.2 Presentation 67
6.3 Diagnostic evaluation 67
6.3.1 Diagnostic investigations for bladder stones 67
6.3.2 Diagnosing the cause of bladder stones 67
6.4 Disease Management 68
6.4.1 Conservative treatment and Indications for active stone removal 68
6.4.2 Medical management of bladder stones 68
6.4.3 Bladder stone interventions 68
6.4.3.1 Suprapubic cystolithotomy 68
6.4.3.2 Transurethral cystolithotripsy 68
6.4.3.2.1 Transurethral cystolithotripsy in adults 68
6.4.3.2.1.1 Lithotripsy modalities used during
transurethral cystolithotripsy in adults 68
6.4.3.2.1.2 Transurethral cystolithotripsy in children 69
6.4.3.3 Percutaneous cystolithotripsy 69
6.4.3.3.1 Percutaneous cystolithotripsy in adults: 69
6.4.3.3.2 Percutaneous cystolithotripsy in children: 69
6.4.3.4 Extracorporeal shock wave lithotripsy 69
6.4.3.4.1 Shock wave lithotripsy in adults 69
6.4.3.4.2 Shock wave lithotripsy in children 70
6.4.3.5 Laparoscopic cystolithotomy 70
6.4.4 Treatment for bladder stones secondary to bladder outlet obstruction in adult
men 70
6.4.5 Special situations 70
6.4.5.1 Neurogenic bladder and stone formation 70
6.4.5.2 Bladder Augmentation 71
6.4.5.3 Urinary diversion 71
6.4.5.4 Treatment of stones in patients with bladder augmentation or urinary
diversion 71
6.5 Bladder stones follow-up 72
6.6 Summary of evidence and recommendations for the treatment of bladder stones 73
7. REFERENCES 75
8. CONFLICT OF INTEREST 118
9. CITATION INFORMATION 119

1. INTRODUCTION
1.1 Aims and scope
The European Association of Urology (EAU) Urolithiasis Guidelines Panel has prepared these guidelines to
help urologists assess evidence-based management of stones/calculi in the urinary tract and incorporate
recommendations into clinical practice. This document covers most aspects of the disease, which is still
a cause of significant morbidity despite technological and scientific advances. The Panel is aware of the
geographical variations in healthcare provision. In addition, information on the management of bladder stones
is now also included in these guidelines.
It must be emphasised that clinical guidelines present the best evidence available to the experts
but following guideline recommendations will not necessarily result in the best outcome. Guidelines can never
replace clinical expertise when making treatment decisions for individual patients, but rather help to focus
decisions - also taking personal values and preferences/individual circumstances of patients into account.
Guidelines are not mandates and do not purport to be a legal standard of care.
1.2 Panel composition

The EAU Urolithiasis Guidelines Panel consists of an international group of clinicians with particular expertise
in this area. All experts involved in the production of this document have submitted potential conflict of interest
statements, which can be viewed on the EAU, website Uroweb: http://uroweb.org/guideline/urolithiasis/.
1.3 Available publications

A quick reference document (Pocket guidelines) is available. This is an abridged versions, which may require
consultation together with the full text versions. Several scientific publications are also available [1-3]. All
documents can be accessed through the EAU website: http://uroweb.org/guideline/urolithiasis/.
1.4 Publication history and summary of changes

1.4.1 Publication history
The EAU Urolithiasis Guidelines were first published in 2000. This 2023 document presents a limited update of
the 2022 version.
1.4.2 Summary of changes

The literature for the entire document has been checked and, wherever relevant, updated (see Methods section 2.1).
References and supporting text have also been refreshed.
The literature for the entire document has been reviewed and, wherever relevant, updated (see Methods
section 2.1) and references and supporting text have also been refreshed. A new recommendation has been
given in section 3.4.7.1 related to endourology techniques for renal stone removal (see below). In addition,
minor updates have been made to figures 4.2, 4.5, 4.6, 4.7 and 4.9.
Recommendation Strength rating

Take a stone culture or urine culture directly from the renal pelvis at time of percutaneous Strong
nephrolithotomy, if possible.
2. METHODS
2.1 Data identification
For the 2023 Urolithiasis Guidelines, new and relevant evidence has been identified, collated, and appraised
through a structured assessment of the literature.
A broad and comprehensive scoping exercise covering all areas of the guideline was performed.
The search was limited to studies representing high levels of evidence only (i.e., systematic reviews with meta-
analysis (MA), randomised controlled trials (RCTs), and prospective non-randomised comparative studies)
published in the English language. The search was restricted to articles published between 1st May 2021 and
9th May 2022. A total of 635 unique records were identified and screened for relevance. A total of 66 new
references have been added to the Urolithiasis 2023 Guidelines publication.

Databases covered by the searches included Medline, EMBASE, Ovid and the Cochrane Libraries.
The search strategy is published online: https://uroweb.org/guidelines/urolithiasis/ publications-appendices.
The chapters on the treatment of bladder stones in adults and children are based on a systematic review [4].
For each recommendation within the guidelines there is an accompanying online strength rating form which
includes an assessment of the benefit to harms ratio and patients’ preferences for each recommendation.
The strength rating forms draw on the guiding principles of the GRADE methodology but do not purport to be
GRADE [5, 6]. Each strength-rating form addresses a number of key elements, namely:
1. the overall quality of the evidence which exists for the recommendation, references used in
this text are graded according to a classification system modified from the Oxford Centre for
Evidence-Based Medicine Levels of Evidence [7];
2. the magnitude of the effect (individual or combined effects);
3. the certainty of the results (precision, consistency, heterogeneity and other statistical or
study related factors);
4. the balance between desirable and undesirable outcomes;
5. the impact of patient values and preferences on the intervention;
6. the certainty of those patient values and preferences.
These key elements are the basis which panels use to define the strength rating of each recommendation.
The strength of each recommendation is represented by the words ‘strong’ or ‘weak’ [8]. The strength of each
recommendation is determined by the balance between desirable and undesirable consequences of alternative
management strategies, the quality of the evidence (including certainty of estimates), and nature and variability
of patient values and preferences.
Additional information can be found in the general Methodology section of this print, and online at
the EAU website: http://www.uroweb.org/guideline/.
A list of associations endorsing the EAU Guidelines can also be viewed online at the above address.
2.2 Review
The 2015 Urolithiasis Guidelines were subjected to peer-review prior to publication. Chapter 6, detailing the
treatment and follow-up of bladder stones was peer reviewed in 2019.
2.3 Future goals

For the 2024 text update the Urolithiasis Guidelines Panel aim to:
• Further evaluate the highest evidence for best clinical practice in endourology.
• Question the accuracy of stone size as the surrogate index on deciding the appropriate treatment of
urinary stones.
• Complete two systematic reviews on:
a) The relation of kidney stones and their treatment on chronic kidney failure and end stage kidney
disease.
b) Patient and personnel radiation protection during endourology.
3. GUIDELINES
3.1 Prevalence, aetiology, risk of recurrence
3.1.1 Introduction
Stone incidence depends on geographical, climatic, ethnic, dietary, and genetic factors. The recurrence risk is
basically determined by the disease or disorder causing the stone formation. Accordingly, the prevalence rates
for urinary stones vary from 1% to 20% [9]. In countries with a high standard of life such as Sweden, Canada or
the USA, renal stone prevalence is notably high (> 10%). For some areas, an increase of more than 37% over
the last 20 years has been reported [10-12]. There is emerging evidence linking nephrolithiasis to the risk of
chronic Kidney disease (CKD) [13].
Stones can be stratified into those caused by: infections, non-infectious causes, genetic defects [14]; or
adverse drug effects (drug stones) (Table 3.1). See also section 3.2.

Table 3.1: Stones classified by aetiology
Non-infection stones
• Calcium oxalate • Calcium phosphate • Uric acid
• Ammonium urate*
Infection stones
• Magnesium ammonium phosphate • Highly carbonated apatite • Ammonium urate
Genetic causes
• Cystine • Xanthine • 2,8-Dihydroxyadenine
Drug stones
*In children in developing countries; in patients with anorexia or laxative-abuse.
3.1.2 Stone composition

Stone composition is the basis for further diagnostic and management decisions. Stones are often formed from
a mixture of substances. Table 3.2 lists the most clinically relevant substances and their mineral components.
Table 3.2: Stone composition

Chemical name Mineral name [15] Chemical formula
Calcium oxalate monohydrate Whewellite CaC2O4.H2O
Calcium oxalate dihydrate Weddelite CaC2O4.2H2O
Basic calcium phosphate Apatite Ca10(PO4)6.(OH)2
Calcium hydroxyl phosphate Carbonate apatite Ca5(PO4)3(OH)
b-tricalcium phosphate Whitlockite Ca3(PO4)2
Carbonate apatite phosphate Dahllite Ca5(PO4)3OH
Calcium hydrogen phosphate dihydrate Brushite CaHPO4.2H2O
Calcium carbonate Aragonite CaCO3
Octacalcium phosphate - Ca8H2(PO4)6.5H2O
Uric acid Uricite C5H4N4O3
Uric acid dihydrate Uricite C5H4O3.2H20
Ammonium urate - NH4C5H3N4O3
Sodium acid urate monohydrate - NaC5H3N4O3.H2O
Magnesium ammonium phosphate hexahydrate Struvite MgNH4PO4.6H2O
Magnesium acid phosphate trihydrate Newberyite -
Magnesium ammonium phosphate monohydrate Dittmarite -
Cystine - -
Xanthine - -
2,8-Dihydroxyadenine - -
Proteins - -
Cholesterol - -
Calcite - -
Potassium urate - -
Trimagnesium phosphate - -
Melamine - -
Matrix - -
Drug stones Active compounds -
crystallising in urine
Foreign body calculi - -
3.1.3 Risk groups for stone formation

The risk status of stone formers should be determined in a holistic way taking into consideration not only the
probability of stone recurrence or regrowth, but also the risk of CKD and mineral and bone disorder (MBD)
[16, 17], and is imperative for pharmacological treatment. About 50% of recurrent stone formers have just one
lifetime recurrence [11, 18]. A recent review of first-time stone formers calculated a recurrence rate of 26% in
five years’ time [19]. Highly recurrent disease is observed in slightly more than 10% of patients. Stone type and
disease severity determine low- or high-risk stone formers (Table 3.3) [20, 21].

Table 3.3: High-risk stone formers [20-36]
General factors
Early onset of urolithiasis (especially children and teenagers)
Familial stone formation
Recurrent stone formers
Short time since last stone episode
Brushite-containing stones (CaHPO4.2H2O)
Uric acid and urate-containing stones
Infection stones
Solitary kidney (the kidney itself does not particularly increase the risk of stone formation, but prevention of
stone recurrence is of crucial importance to avoid acute renal failure)
Chronic Kidney Disease (CKD)
Diseases associated with stone formation
Hyperparathyroidism
Metabolic syndrome
Mineral Bone Disorder (MBD)
Nephrocalcinosis
Polycystic kidney disease (PKD)
Gastrointestinal diseases (i.e., jejuno-ileal bypass, intestinal resection, Crohn’s disease, malabsorptive
conditions, enteric hyperoxaluria after urinary diversion, exocrine pancreatic insufficiency) and bariatric
surgery
Increased levels of vitamin D
Sarcoidosis
Spinal cord injury, neurogenic bladder
Genetically determined stone formation
Cystinuria (type A, B and AB)
Primary hyperoxaluria (PH)
Renal tubular acidosis (RTA) type I
2,8-Dihydroxyadeninuria
Xanthinuria
Lesch-Nyhan syndrome
Cystic fibrosis
Drug-induced stone formation (see Table 4.11)
Anatomical abnormalities associated with stone formation
Medullary sponge kidney (tubular ectasia)
Ureteropelvic junction (UPJ) obstruction
Calyceal diverticulum, calyceal cyst
Ureteral stricture
Vesico-uretero-renal reflux
Horseshoe kidney
Ureterocele
Environmental and professional factors
High ambient temperatures
Chronic lead and cadmium exposure
A comprehensive evaluation of stone risk in patients should also include the risk of developing CKD, end-stage
kidney disease (ESKD), and MBD (Tables 3.4, 3.5 and 3.6) [16]. Urolithiasis can compromise renal function
because of the renal stone (obstruction, infection), renal tissue damage due to the primary condition causing
stone formation (some genetic diseases, nephrocalcinosis, enteric hyperoxaluria, etc.), or urological treatments
for the condition [16]. Certain risk factors have been shown to be associated with such a risk in stone formers,
as shown below.

Table 3.4 Risk factors for CKD and ESKD in stone formers
Risk factors for CKD/ESKD in stone formers
Female gender
Overweight
Frequent urinary tract infection (UTI)
Struvite stones
Acquired single kidney
Neurogenic bladder
Previous obstructive nephropathy
Ileal conduit
Furthermore, some specific kinds of urolithiasis also carry a particular risk of developing CKD/ESKD as shown
below.
Table 3.5 Risk factors for CKD and renal stones

Risk of chronic kidney disease and renal stones
• Possible risk of CKD
Xanthine stones
Indinavir stones
Distal renal tubular acidosis (incomplete)
Primary hyperparathyroidism
Eating disorders and laxative abuse
Medullary sponge kidney
• Moderate risk of CKD
Brushite stones
2,8-Dihydroxyadenine stones
Sarcoidosis
Pyelo-ureteral or ureteral strictures
• High risk of CKD
Cystine stones
Struvite stones
Stones in a single kidney
Distal renal tubular acidosis (complete)
Secondary hyperoxaluria (bariatric surgery, inflammatory bowel disease, bowel resection and
malabsorptive syndromes)
Other forms of nephrocalcinosis (often associated with genetic conditions with hypercalciuria)
Anatomical abnormalities of the kidney and urinary tract (for example, horseshoe kidney, ureterocele
and vesicoureteral reflux)
Neurological bladder
• Very high risk of CKD
Primary hyperoxaluria
Autosomal dominant polycystic kidney
Table 3.6 Risk factors for metabolic bone disease and calcium renal stones
Risk of metabolic bone disease and calcium renal stones
• Distal renal tubular acidosis (complete or incomplete)
• Medullary sponge kidney
• Primary hyperparathyroidism
• Malabsorptive syndromes
• Fasting hypercalciuria
• Genetic disorders
3.2 Classification of stones

Urinary stones can be classified according to size, location, X-ray characteristics, aetiology of formation,
composition, and risk of recurrence [11, 37, 38].

3.2.1 Stone size
Stone size is usually given in one or two dimensions, and stratified into those measuring up to 5, 5-10, 10-20,
and > 20 mm in largest diameter.
3.2.2 Stone location

Stones can be classified according to anatomical position: upper, middle, or lower calyx; renal pelvis; upper,
middle, or distal ureter; and urinary bladder.
3.2.3 X-ray characteristics

Stones can be classified according to plain X-ray appearance [kidney-ureter-bladder (KUB) radiography] (Table
3.6), which varies according to mineral composition [38]. Non-contrast-enhanced computed tomography
(NCCT) can be used to classify stones according to density, inner structure, and composition, which can affect
treatment decisions (Section 3.3) [37, 38].
Table 3.7: X-ray characteristics

Radiopaque Poor radiopacity Radiolucent
Calcium oxalate dehydrate Magnesium ammonium phosphate Uric acid
Calcium oxalate monohydrate Apatite Ammonium urate
Calcium phosphates Cystine Xanthine
2,8-Dihydroxyadenine
Drug-stones (Section 4.11)
3.3 Diagnostic evaluation

3.3.1 Diagnostic imaging
The most appropriate imaging modality will be determined by the clinical situation, which will differ depending
on if a ureteral or a renal stone is suspected.
Standard evaluation includes a detailed medical history and physical examination. Patients with
ureteral stones usually present with loin pain, vomiting, and sometimes fever, but may also be asymptomatic
[39]. Immediate evaluation is indicated in patients with solitary kidney, fever or when there is doubt regarding
a diagnosis of renal colic. Ultrasound (US) should be used as the primary diagnostic imaging tool, although
pain relief, or any other emergency measures, should not be delayed by imaging assessments. Ultrasound is
safe (no risk of radiation), reproducible and inexpensive. It can identify stones located in the calyces, pelvis,
and pyeloureteric and vesico-ureteral junctions (US with filled bladder), as well as in patients with upper urinary
tract (UUT) dilatation. Ultrasound has a sensitivity of 45% and specificity of 94% for ureteral stones and a
sensitivity of 45% and specificity of 88% for renal stones [40, 41].
The sensitivity and specificity of KUB is 44-77% [42]. Kidney-ureter-bladder radiography should not
be performed if NCCT is being considered [43]; however, it is helpful in differentiating between radiolucent and
radiopaque stones and should be used for comparison during follow-up.
3.3.1.1 Evaluation of patients with acute flank pain/suspected ureteral stones

Non-contrast-enhanced computed tomography (CT) has become the standard for diagnosing acute flank pain
and has replaced intravenous urography (IVU). Non-contrast-enhanced CT can determine stone diameter and
density. When stones are absent, the cause of abdominal pain should be identified. In evaluating patients with
suspected acute urolithiasis, NCCT is significantly more accurate than IVU or US [44].
Non-contrast-enhanced CT can detect uric acid and xanthine stones, which are radiolucent on plain films,
but not indinavir stones [45]. Non-contrast-enhanced CT can determine stone density, inner structure of the
stone, skin-to-stone distance, and surrounding anatomy; all of which affect selection of treatment modality
[38, 46-48]. The advantage of non-contrast imaging must be balanced against loss of information on renal
function and urinary collecting system anatomy, as well as higher radiation dose [49-52].
Radiation risk can be reduced by low-dose CT, which may, however, be difficult to introduce in
standard clinical practice [53-57]. In patients with a body mass index (BMI) < 30, low-dose CT has been shown
to have a sensitivity of 86% for detecting ureteral stones < 3 mm and 100% for calculi > 3 mm [58]. A meta-
analysis (MA) of prospective studies [55] has shown that low-dose CT diagnosed urolithiasis with a pooled
sensitivity of 93.1% (95% confidence interval [CI]: 91.5-94.4), and a specificity of 96.6% (95% CI: 95.1-97.7%).
Dual-energy CT can differentiate uric acid containing stones from calcium-containing stones [59, 60].

Summary of evidence LE
Non-contrast-enhanced CT is used to confirm stone diagnosis in patients with acute flank pain, as it is 1a
superior to IVU.
Enhanced CT enables 3D reconstruction of the collecting system, as well as measurement of stone 2a
density and skin-to-stone distance.
Recommendations Strength rating

Immediate imaging is indicated with fever or solitary kidney, and when diagnosis is doubtful. Strong
Use non-contrast-enhanced computed tomography to confirm stone diagnosis in patients Strong
with acute flank pain following initial ultrasound assessment.
Perform a contrast study if stone removal is planned and the anatomy of the renal collecting Strong
system needs to be assessed.
3.3.2 Diagnostics - metabolism-related

Besides imaging, each emergency patient with urolithiasis needs a succinct biochemical work-up of urine and
blood test. At this point, no distinction is made between high- and low-risk patients for stone formation.
3.3.2.1 Basic laboratory analysis - non-emergency urolithiasis patients

Biochemical work-up is similar for all stone patients. However, if no intervention is planned, examination of
sodium, potassium, C-reactive protein (CRP), and blood coagulation time can be omitted. Only patients at high
risk for stone recurrence should undergo a more specific analytical programme [21]. Stone-specific metabolic
evaluation is described in Chapter 4.
The easiest method for diagnosing stones is by analysis of a passed stone using a validated method
as listed in section 3.3.2.3. Once the mineral composition is known, a potential metabolic disorder can be
identified.
3.3.2.2 Analysis of stone composition

Stone analysis should be performed in all first-time stone formers.
In clinical practice, repeat stone analysis is needed in the case of:

• recurrence under pharmacological prevention;
• early recurrence after interventional therapy with complete stone clearance;
• late recurrence after a prolonged stone-free period [61, 62].
Patients should be instructed to filter their urine to retrieve a concrement for analysis. Stone passage and
restoration of normal renal function should be confirmed.
The preferred analytical procedures are infrared spectroscopy (IRS) or X-ray diffraction (XRD)
[63-65]. Equivalent results can be obtained by polarisation microscopy. Chemical analysis (wet chemistry) is
generally deemed to be obsolete [63, 66].
3.3.2.3 Recommendations for laboratory examinations and stone analysis [21, 27, 67-69]

Urine
Dipstick test of spot urine sample: Weak
• red cells;
• white cells;
• nitrites;
• approximate urine pH;
• urine microscopy and/or culture.
Blood
Serum blood sample: Strong
• creatinine;
• uric acid;
• (ionised) calcium;
• sodium;
• potassium;
• blood cell count;
• C-reactive protein.

Perform a coagulation test (partial thromboplastin time and international normalised ratio) if Strong
intervention is likely or planned.
Perform stone analysis in first-time formers using a valid procedure (X-ray diffraction or Strong
infrared spectroscopy).
Repeat stone analysis in patients presenting with: Strong
• recurrent stones despite drug therapy;
• early recurrence after complete stone clearance;
• late recurrence after a long stone-free period because stone composition may change.
3.3.3 Diagnosis in special groups and conditions

3.3.3.1 Diagnostic imaging during pregnancy
In pregnant women radiation exposure may cause non-stochastic (teratogenesis) or stochastic (carcinogenesis/
mutagenesis) effects. Teratogenic effects are cumulative with increasing dose and require a threshold dose
(< 50 mGy are considered as safe) and depend on the gestation age (minimum risk prior to 8th week and after
the 23rd week). Carcinogenesis (doses even < 10 mGy present a risk) and mutagenesis (500-1000 mGy doses
are required, far in excess of the doses in common radiographic studies) get worse with increasing dose but
they do not require a dose threshold and are not dependent on gestational age [70].
There is no imaging modality that should be routinely repeated in pregnant women. Scientific societies and
organisations agree on the safety of diagnostic evaluation when US [71], X-ray imaging [72, 73], and MRI
[74, 75] are used as and when indicated [76-82]. A radiographic procedure should not be withheld from a
pregnant woman if the procedure is clearly indicated and doing so will affect her medical care.
It is generally recommended that an investigation resulting in an absorbed dose to the foetus of
greater than 0.5 mGy requires justification.
Ultrasound (when necessary, using changes in renal resistive index and transvaginal/transabdominal US with a
full bladder) has become the primary radiological diagnostic tool when evaluating pregnant patients suspected
of renal colic. However, normal physiological changes in pregnancy can mimic ureteral obstruction [78-80].
Magnetic resonance imaging can be used, as a second-line option [76], to define the level of urinary
tract obstruction, and to visualise stones as a filling defect [74]. As 3 Tesla (T) MRI has not been evaluated
in pregnancy, the use of 1.5T is currently recommended [77, 82]. The use of gadolinium is not routinely
recommended in pregnancy to avoid toxic effects to the embryo [78].
For the detection of urolithiasis during pregnancy, low-dose CT is associated with a higher positive
predictive value (95.8%), compared to MRI (80%) and US (77%). As per White et al., low-dose CT offers
improved diagnostic accuracy that can avoid negative interventions such as ureteroscopy [83]. Although low-
dose CT protocols reduce the radiation exposure, judicious use is currently recommended in pregnant women
as a last-line option [78].
Only low-level data exist for imaging in pregnant women supporting US and MRI. 3

Use ultrasound as the preferred method of imaging in pregnant women. Strong
Use magnetic resonance imaging as a second-line imaging modality in pregnant women. Strong
Use low-dose computed tomography as a last-line option in pregnant women. Strong
3.3.3.2 Diagnostic imaging in children

Children with urinary stones have a high risk of recurrence; therefore, standard diagnostic procedures
for high-risk patients apply, including a valid stone analysis (Section 3.1.3 and Chapter 4). The most
common nonmetabolic disorders facilitating stone formation are vesico-ureteral reflux (VUR), UPJ obstruction,
neurogenic bladder, and other voiding difficulties [84].
When selecting diagnostic procedures to identify urolithiasis in children, it should be remembered
that these patients might be uncooperative, require anaesthesia, and may be sensitive to ionising radiation.
Again, the principle of ALARA (As Low As Reasonably Achievable) should be observed [85-87].
Ultrasound
Ultrasound is the primary imaging technique [88] in children. Its advantages are absence of radiation and no need
for anaesthesia. Imaging should include both the fluid-filled bladder with adjoining portion of the ureters, as well

as the upper ureter [89-93]. Colour Doppler US shows differences in the ureteral jet [90] and resistive index of the
arciform arteries of both kidneys, which are indicative of the grade of obstruction [91]. Nevertheless, US fails to
identify stones in > 40% of children [92-95] and provides limited information on renal function.
Plain films (KUB radiography)

Kidney-ureter-bladder radiography can help to identify stones and their radiopacity and facilitate follow-up.
Intravenous urography
The radiation dose for IVU is comparable to that for voiding cysto-urethrography (0.33 mSV) [96]. However, the
need for contrast medium injection is a major drawback.
Non-contrast-enhanced computed tomography

Recent low-dose CT protocols have been shown to significantly reduce radiation exposure [52, 97, 98]. In
children, only 5% of stones escape detection by NCCT [90, 98, 99]. Sedation or anaesthesia is rarely needed
with modern high-speed CT equipment.
Magnetic resonance urography

Magnetic resonance urography (MRU) cannot be used to detect urinary stones. However, it might provide
detailed anatomical information about the urinary collecting system, the location of an obstruction or stenosis
in the ureter, and renal parenchymal morphology [100].
3.3.3.2.1 Summary of evidence and recommendations for diagnostic imaging in children
Ultrasound is the first-line imaging modality in children when a stone is suspected; it should include 2b
the kidney, fluid-filled bladder, and the ureter next to the kidney and the (filled) bladder.
A kidney-ureter-bladder radiography (or low-dose NCCT) is an alternative investigation if US will not 2b
provide the required information.

Complete a metabolic evaluation based on stone analysis in all children. Strong
Collect stone material for analysis to classify the stone type. Strong
Perform ultrasound as first-line imaging modality in children when a stone is suspected; it Strong
should include the kidney, fluid-filled bladder, and the ureter.
Perform a kidney-ureter-bladder radiography (or low-dose non-contrast-enhanced Strong
computed tomography) if ultrasound will not provide the required information.
3.4 Disease Management

The treatment of urolithiasis is based on many parameters and is individualised for each patient. Parameters
such as the size, number, location, and constitution of the stones are cornerstones for deciding the treatment.
In addition, the morphology, shape, volume, mobility, and hardness of the stone should be considered. Finally,
the anatomy and compliance of the entire pelvic-calyceal system should be assessed for each patient. The
design of therapeutic algorithms including all of the above parameters is difficult mainly due to the great
diversity of lithiasis disease per patient. Furthermore, there is a significant lack of comparative clinical studies
to support development of algorithms using parameters other than stone size and composition.
3.4.1 Renal colic

Pain relief
Non-steroidal anti-inflammatory drugs (NSAIDs) (including metamizoledipyrone), and paracetamol are effective
in patients with acute stone colic [101], and have better analgesic efficacy than opioids [102]. Ibuprofen
compared to ketorolac is a more rapid acting drug in controlling pain caused by renal colic with a similar side
effect profile [103].
Pain relief from intramuscular (i.m.) diclofenac compared favourably with those from intravenous (i.v.)
ibuprofen and i.v. ketorolac; however, no recommendation can be given due to the way in which the results
have been reported [104]. The addition of antispasmodics to NSAIDs does not result in better pain control.
Patients receiving NSAIDs are less likely to require further analgesia in the short term. It should be taken into
consideration that the use of diclofenac and ibuprofen increased major coronary events [101, 102]. Diclofenac

is contraindicated in patients with congestive heart failure (New York Heart Association class II-IV), ischaemic
heart disease and peripheral arterial- and cerebrovascular disease. Patients with significant risk factors for
cardiovascular events should be treated with diclofenac only after careful consideration. As risks increase with
dose and duration, the lowest effective dose should be used for the shortest duration [105, 106].
In a RCT including 150 patients, Intradermal sterile water injection (ISWI) and diclofenac (i.m.)
were shown equally effective for pain relief in acute renal colic. Intradermal sterile water injection may be an
alternative to NSAIDs in pregnant patients or others where NSAIDs are contra-indicated [107].
Opioids, particularly pethidine, are associated with a high rate of vomiting compared to NSAIDs and carry
a greater likelihood of further analgesia being needed [101, 108] (see below). If an opioid is used, it is
recommended that it is not pethidine. Combination of opioids and NSAIDs increase analgetic effect compare
to opioids alone [109]. Data on other types of non-opioid and non-NSAID medication is increasing. Ketamine
in combination with morphine, compared to morphine alone, leads to morphine consumption reduction, less
pain, nausea and vomiting [110-112]. Patients receiving ketamine and NSAIDs attained greater reduction in
pain scores with less side effects, and better functional state, as well as less further analgesia requirement
than those administered pethidine [113]. However, when comparing ketamine vs. NSAID (ketorolac) alone,
equal efficacy but higher rates of dizziness, agitation and hypertension with ketamine were observed [114].
Conflicting results have been reported regarding the utility of intravenous lidocaine. Acupuncture seems to be
effective in renal colic alone or in combination, but there is limited data [115, 116].
Prevention of recurrent renal colic

Facilitation of passage of ureteral stones is discussed in Section 3.4.9. For patients with ureteral stones that
are expected to pass spontaneously, NSAID tablets or suppositories (e.g., diclofenac sodium, 100-150 mg/day,
3-10 days) may help reduce inflammation and the risk of recurrent pain [117, 118]. Although diclofenac can affect
renal function in patients with already reduced function, it has no functional effect in patients with normal renal
function [119].
The systematic review and MA by Hollingsworth et al., [120] addressed pain reduction as a secondary
outcome and concluded that medical expulsive therapy (MET) seems efficacious in reducing pain episodes of
patients with ureteral stones.
If analgesia cannot be achieved medically, drainage, using stenting, percutaneous nephrostomy, or
stone removal, is indicated [121].
3.4.1.1 Summary of evidence and recommendations for the management of renal colic
Non-steroidal anti-inflammatory drugs are very effective in treating renal colic and are superior to opioids. 1b
For symptomatic ureteral stones, stone removal as first-line treatment is a feasible option in selected 1b
patients.

Offer a non-steroidal anti-inflammatory as the first drug of choice; e.g., metamizole* Strong
(dipyrone); alternatively paracetamol or, depending on cardiovascular risk factors,
diclofenac**, indomethacin or ibuprofen***.
Offer opioids (hydromorphine, pentazocine or tramadol) as a second choice. Weak
Offer renal decompression or ureteroscopic stone removal in case of analgesic refractory Strong
colic pain.
* M aximum single oral dose recommended 1000 mg, total daily dose up to 5000 mg, not recommended in the
last three months of pregnancy [122].
** Affects glomerular filtration rate (GFR) in patients with reduced renal function.
*** R
ecommended to counteract recurrent pain after ureteral colic.
3.4.2 Management of sepsis and/or anuria in obstructed kidney

The obstructed kidney with all signs of urinary tract infection (UTI) and/or anuria is a urological emergency.
Urgent decompression is often necessary to prevent further complications in infected hydronephrosis
secondary to stone-induced, unilateral or bilateral, renal obstruction.

Decompression
Currently, there are two options for urgent decompression of obstructed collecting systems [123]:
• placement of an indwelling ureteral stent;
• percutaneous placement of a nephrostomy tube.
There is little evidence to support the superiority of percutaneous nephrostomy over retrograde stenting for
primary treatment of infected hydronephrosis. There is no good quality evidence to suggest that ureteral
stenting has more complications than percutaneous nephrostomy [124, 125].
Only one RCT [126] compared different modalities of decompression of acute infected
hydronephrosis. Two other small RCTs compared stenting vs. nephrostomy tube placement in patients with
acute kidney injury and demonstrated both to be effective in decompressing the collecting system [127,
128]. The complications of percutaneous nephrostomy insertion have been reported consistently, but those
of ureteral stent insertion are less well described [124]. Definitive stone removal should be delayed until the
infection is cleared following a complete course of antimicrobial therapy. A small RCT showed the feasibility of
immediate ureteroscopic stone removal combined with an appropriate antibiotic regimen; however, at the cost
of longer hospital stay and higher analgesic requirements [129].
Further measures
Following urgent decompression of the obstructed and infected urinary collecting system, both urine- and
blood samples should be sent for culture-antibiogram sensitivity testing and antibiotics should be initiated
immediately thereafter or continued, if initiated prior to testing. The regimen should be re-evaluated in the light
of the culture-antibiogram results. Although clinically well accepted, the impact of a second antibiogram test on
treatment outcome has not yet been evaluated. Intensive care might become necessary [130].
3.4.2.1 Summary of evidence and recommendations for the management of sepsis and anuria
For decompression of the renal collecting system, ureteral stents and percutaneous nephrostomy 1b
catheters are equally effective.

Urgently decompress the collecting system in case of sepsis with obstructing stones, using Strong
percutaneous drainage or ureteral stenting.
Delay definitive treatment of the stone until sepsis is resolved. Strong
Collect (again) urine for antibiogram test following decompression. Strong
Start antibiotics immediately (+ intensive care, if necessary). Strong
Re-evaluate antibiotic regimen following antibiogram findings. Strong
3.4.3 Medical expulsive therapy

Several drug classes including α-blockers, calcium channel inhibitors and phosphodiesterase type 5 inhibitors
(PDEI-5) are used for MET [131-134]. A class effect of α-blockers in MET has been demonstrated in
MAs although this is an off-label indication [135-137]. However, there is contradictory evidence between
these studies and several well-designed, multicentre, placebo-controlled, double-blinded randomised studies
showing limited, or no, benefit using α-blockers, besides some advantage for distal ureteral stones > 5 mm
[138-142]. Based on studies with a limited number of patients [134, 135, 143, 144], no recommendation for the
use of PDEI-5 or corticosteroids in combination with α-blockers in MET can be made. The panel concludes
that MET using α-blockers seems efficacious in the treatment of patients with distal ureteral stones > 5 mm
who are amenable to conservative management. Medical expulsive therapy in special situations is addressed in
the relevant chapters.
3.4.3.1 Summary of evidence and recommendations for MET
Medical expulsive therapy seems to be efficacious for treating patients with ureteral stones who are 1a
amenable to conservative management. The greatest benefit might be among those with > 5 mm
(distal) ureteral stones.
Insufficient data exist to support the use of PDEI-5 or corticosteroids in combination with α-blockers 2a
as an accelerating adjunct.

Alpha-blockers increase stone expulsion rates in distal ureteral stones > 5 mm. 1a
A class effect of α-blockers has been demonstrated. 1a

Consider α-blockers as medical expulsive therapy as one of the treatment options for Strong
(distal) ureteral stones > 5 mm.
3.4.4 Chemolysis
Percutaneous irrigation chemolysis
Percutaneous chemolysis is rarely used nowadays, for practical reasons. Percutaneous irrigation chemolysis
may be an option for infection-stones and theoretically also for uric acid stones. For dissolution of struvite
stones, Suby’s G solution (10% hemiacidrin; pH 3.5-4) can be used. The method has been described in case
series and literature reviews [145-147].
Oral chemolysis
Stones composed of uric acid, but not sodium or ammonium urate stones, can be dissolved by oral
chemolysis. Prior stone analysis may provide information on stone composition. Urinary pH measurement and
X-ray characteristics can provide information on the type of stone.
Oral chemolitholysis is based on alkalinisation of urine by application of alkaline citrate or sodium
bicarbonate. The pH should be adjusted to 7.0-7.2. Chemolysis is more effective at a higher pH, which might,
however, promote calcium phosphate stone formation. Patients will need to adjust the dosage of alkalising
medication by self-monitoring the pH of their urine. No RCTs are available for this therapy, which has been in
use for decades. Rodman, et al., [148] reviewed the principles and provided guidance to its clinical use, which
was supported by Becker, et al., in 2007 [149] and Elsawy et al. in 2019 [150]. Monitoring of radiolucent stones
during therapy is the domain of US; however, repeat-NCCT might be necessary [148, 149].
In the case of uric acid obstruction of the collecting system, oral chemolysis in combination with
urinary drainage is indicated [151]. A combination of alkalinisation with tamsulosin can increase the frequency
of spontaneous passage of distal ureteral uric acid stones as shown in one RCT for stones > 5 mm [151].
Additional shock wave lithotripsy (SWL) might help to improve the results but evidence is weak [152].
3.4.4.1 Summary of evidence and recommendations for chemolysis
Irrigation chemolysis has been used in limited clinical settings to dissolve struvite stones. 3
Uric acid stones > 5mm can be dissolved based on oral alkalinisation of the urine above 7.0. 3
For obstructing uric acid stones, a combination of oral chemolysis with tamsulosin is more effective 1b
than each substance alone, particularly in stones > 8 mm.
Recommendations (oral chemolysis of uric acid stones) Strength rating

Inform the patient how to monitor urine-pH by dipstick and to modify the dosage of alkalising Strong
medication according to urine pH, as changes in urine pH are a direct consequence of such
medication.
Carefully monitor patients during/after oral chemolysis of uric acid stones. Strong
Combine oral chemolysis with tamsulosin in case of (larger) ureteral stones (if active Weak
intervention is not indicated).
3.4.5 Extracorporeal shock wave lithotripsy (ESWL)

The success of SWL depends on the efficacy of the lithotripter and the following factors:
• size, location (ureteral, pelvic or calyceal), and composition (hardness) of the stones (Section 3.4.9.3);
• patient’s habitus (Section 3.4.10.3);
• performance of SWL (best practice, see below).
Each of these factors significantly influences the retreatment rate and final outcome of SWL.
Best clinical practice

Stenting
Routine use of internal stents before SWL does not improve stone free rates (SFRs), nor lowers the number of
auxiliary treatments. It may, however, reduce formation of steinstrasse [153-156].

Pacemaker
Patients with a pacemaker can be treated with SWL, provided that appropriate technical precautions are taken.
Patients with implanted cardioverter defibrillators must be managed with special care (firing mode temporarily
reprogrammed during SWL treatment). However, this might not be necessary with new-generation lithotripters [157].
Shock wave rate

Lowering shock wave frequency from 120 to 60-90 shock waves/min improves SFRs [158-166]. Ultraslow
frequency 30 shock waves/min may increase SFR [167]. Tissue damage increases with shock wave frequency
[168-171].
Number of shock waves, energy setting and repeat treatment sessions

The number of shock waves that can be delivered at each session depends on the type of lithotripter and
shock wave power. There is no consensus on the maximum number of shock waves [172]. Starting SWL on a
lower energy setting with stepwise power (and SWL sequence) ramping can achieve vasoconstriction during
treatment [168], which prevents renal injury [173-175]. Animal studies [176] and a prospective randomised
study [177] have shown better SFRs (96% vs. 72%) using stepwise power ramping, but no difference has been
found for fragmentation or evidence of complications after SWL, irrespective of whether ramping was used
[178, 179].
There are no conclusive data on the intervals required between repeated SWL sessions. However,
clinical experience indicates that repeat sessions are feasible (within one day for ureteral stones) [180].
Improvement of acoustic coupling

Proper acoustic coupling between the cushion of the treatment head and the patient’s skin is important.
Defects (air pockets) in the coupling gel deflect 99% of shock waves [181]. Ultrasound gel is probably the most
widely-used agent available as a lithotripsy coupling agent [182].
Procedural control
Results of treatment are operator dependent, and experienced clinicians obtain better results. During the
procedure, careful imaging control of localisation contributes to outcome quality [183].
Pain Control
Careful control of pain during treatment is necessary to limit pain-induced movements and excessive respiratory
excursions [184-187].
Antibiotic prophylaxis
No standard antibiotic prophylaxis before SWL is recommended. However, prophylaxis is recommended in the
case of internal stent placement ahead of anticipated treatments and in the presence of increased bacterial
burden (e.g., indwelling catheter, nephrostomy tube, or infectious stones) [68, 188, 189].
Medical therapy after extracorporeal shock wave lithotripsy

Despite conflicting results, most RCTs and several MAs support MET after SWL for ureteral or renal stones as
an adjunct to expedite expulsion and to increase SFRs. Medical expulsion therapy might also reduce analgesic
requirements [190-199].
Post-treatment management
Mechanical percussion and diuretic therapy can significantly improve SFRs and accelerate stone passage after
SWL [200-203].
Complications of extracorporeal shock wave lithotripsy

Compared to percutaneous nephrolithotomy (PNL) and ureteroscopy (URS), there are fewer overall
complications with SWL [204, 205] (Table 3.8). The relationship between SWL and hypertension or diabetes
is unclear. Published data are contradictory; however, no evidence exists supporting the hypothesis that SWL
may cause long-term adverse effects [206-212].

Table 3.8: Shock wave lithotripsy-related complications [213-227]
Complications % Reference
Related to stone Steinstrasse 4–7 [225-227]
fragments Regrowth of residual 21 – 59 [214, 215]
fragments
Renal colic 2–4 [216]
Infections Bacteriuria in non- 7.7 – 23 [214, 217]
infection stones
Sepsis 1 – 2.7 [214, 217]
Tissue effect Renal Haematoma, symptomatic <1 [218]
Haematoma, asymptomatic 4 – 19 [218]
Cardiovascular Dysrhythmia 11 – 59 [214, 219]
Morbid cardiac events Case reports [214, 219]
Gastrointestinal Bowel perforation Case reports [220-222]
Liver, spleen haematoma Case reports [213, 222-224]
3.4.5.1 Summary of evidence and recommendations for SWL
Stepwise power ramping prevents renal injury. 1b
Clinical experience has shown that repeat sessions are feasible (within one day for ureteral stones). 4
Optimal shock wave frequency is 1.0 to 1.5 Hz. 1a
Proper acoustic coupling between the cushion of the treatment head and the patient’s skin is important. 2
Careful imaging control of localisation of stone contributes to outcome of treatment. 2a
Careful control of pain during treatment is necessary to limit pain-induced movements and excessive 1a
respiratory excursions.
Antibiotic prophylaxis is recommended in the case of internal stent placement, infected stones, or 1a
bacteriuria.

Ensure correct use of the coupling agent because this is crucial for effective shock wave Strong
transportation.
Maintain careful fluoroscopic and/or ultrasonographic monitoring during shock wave Strong
lithotripsy (SWL).
Use proper analgesia because it improves treatment results by limiting pain-induced Strong
movements and excessive respiratory excursions.
Prescribe antibiotics prior to SWL in the case of infected stones or bacteriuria. Strong
3.4.6 Ureteroscopy (retrograde and antegrade)

The current standard for rigid ureteroscopes is a tip diameter of < 8 French (F). Rigid URS can be used for the
whole ureter [206]. However, technical improvements, as well as the availability of digital scopes, also favour
the use of flexible ureteroscopes in the ureter [228].
Percutaneous antegrade removal of ureteral stones is a consideration in selected cases, i.e. large
(> 15 mm), impacted proximal ureteral calculi in a dilated renal collecting system [229-231], or when the ureter
is not amenable to retrograde manipulation [231-235].
Ureteroscopy for renal stones (RIRS)

Technical improvements including endoscope miniaturisation, improved deflection mechanism, enhanced
optical quality and tools, and introduction of disposables have led to an increased use of URS for both renal
and ureteral stones. Major technological progress has been achieved for RIRS. A recent systematic review
addressing renal stones > 2 cm showed a cumulative SFR of 91% with 1.45 procedures/patient; 4.5% of the
complications were > Clavien 3 [228, 236, 237]. Digital scopes demonstrate shorter operation times due to the
improvement in image quality [236].
Stones that cannot be extracted directly must be disintegrated. If it is difficult to access stones
within the lower renal pole that need disintegration; it may help to displace them into a more accessible
calyx [238].

Best clinical practice in ureteroscopy
Access to the upper urinary tract
Most interventions are performed under general anaesthesia, although local or spinal anaesthesia is possible
[239]. Intravenous sedation is suitable for female patients with distal ureteral stones [240]. Antegrade URS is an
option for large, impacted, proximal ureteral calculi [229-231, 241]. Reduction of flexible ureteroscope diameter
may provide similar vision, deflection, and manoeuvrability to standard flexible ureteroscopes potentially with
improved ureteric access [242]. Disposable ureteroscopes provides similar safety and clinical effectiveness to
reusable scopes. Concerns regarding the cost effectiveness and environmental sustainability remain [243-245].
Safety aspects
Fluoroscopic equipment must be available in the operating room. The Panel recommend placement of a safety
wire, even though some groups have demonstrated that URS can be performed without it [246-250]. Balloon
and plastic dilators should be available, if necessary.
Prior rigid URS can be helpful for optical dilatation followed by flexible URS, if necessary. If ureteral access is
not possible, insertion of a JJ stent followed by URS after seven to fourteen days offers an alternative [251].
Bilateral URS during the same session is feasible resulting in equivalent-to-lower SFRs, but slightly higher
overall complication rates (mostly minor, Clavien 1 and 2) [252, 253].
Difficult lower pole anatomy such as steep infundibulopelvic angle predisposes to failure during
RIRS [254]. Prolonged operative times are linked to increased complication rates in ureteroscopy, and efforts
must be made to keep it below 90 minutes [255].
Ureteral access sheaths

Hydrophilic-coated ureteral access sheaths, which are available in different calibres (inner diameter from 9 F
upwards), can be inserted (via a guide wire) with the tip placed in the proximal ureter.
Ureteral access sheaths allow easy, multiple, access to the UUT and therefore significantly facilitate
URS. The use of ureteral access sheaths improves vision by establishing a continuous outflow, decreases
intrarenal pressure, and potentially reduces operating time [256, 257].
The insertion of ureteral access sheaths may lead to ureteral damage, the risk is lowest in presented
systems [258]. No data on long-term side effects are available [258, 259]. Whilst larger cohort series showed
no difference in SFRs and ureteral damage (stricture rates of about 1.8%), they did show lower post-operative
infectious complications [260, 261]. The use of ureteral access sheath is safe and can be useful for large and
multiple renal stones or if long procedural time is expected [262].
Stone extraction
The aim of URS is complete stone removal. “Dust and go” strategies should be limited to the treatment of large
(renal) stones [263]. Stones can be extracted by endoscopic forceps or baskets. Only baskets made of nitinol
can be used for flexible URS [264].
Intracorporeal lithotripsy
The most effective lithotripsy system is the holmium: yttrium-aluminium-garnet (Ho:YAG) laser, which is
currently the optimum standard for URS and flexible nephroscopy (Section 3.4.6), because it is effective in all
stone types [265, 266]. Compared to low-power lasers, high-power laser reduces procedural time although the
reported difference in clinical outcomes were non-significant [267]. J Pneumatic and US systems can be used
with high disintegration efficacy in rigid URS [268, 269]. However, stone migration into the kidney is a common
problem, which can be prevented by placement of special anti-migration tools proximal of the stone [270].
Medical expulsion therapy following Ho:YAG laser lithotripsy increases SFRs and reduces colic episodes [271].
Thulium fibre laser (TFL) for stone disease has a promising role, offers good clinical outcomes, which seem
to be comparable to Ho:YAG laser (holmium) laser. More comparative clinical studies are however needed
between these two modalities [272, 273].
Stenting before and after URS

Routine stenting is not necessary before URS. Despite a complete lack of RCTs on this subject, a
meta-analysis has been performed, demonstrating that pre-stenting may improve the stone free rate of
ureteroscopic treatment of renal stones, but not of ureteral stones [274]. Although it may facilitate ureteroscopic
management of stones and increase success in access sheath placement, intra-operative complications were
not significantly different [274, 275]. One should also take into account that pre-stenting also causes the patient
to experience stent-related symptoms during the time the stent is indwelling, prior to a procedure.
Randomised prospective trials have found that routine stenting after uncomplicated URS (complete stone

removal) is not necessary; stenting might be associated with higher post-operative morbidity and costs [276-279].
A ureteral catheter with a shorter indwelling time (one day) may also be used, with similar results [280].
Stents should be inserted in patients who are at increased risk of complications (e.g., ureteral
trauma, residual fragments, bleeding, perforation, UTIs, or pregnancy), and in all doubtful cases, to avoid
stressful emergencies. The ideal duration of stenting is not known. Most urologists favour one to two weeks
after URS. Alpha-blockers reduce the morbidity of ureteral stents and increase tolerability [281, 282].
Medical expulsive therapy before and after ureteroscopy

Medical expulsion therapy before URS might reduce the risk for intra-operative ureteral dilatation, protect
against ureteral injury and increase stone free rates four weeks after URS [283]. Medical expulsion therapy
following Ho:YAG laser lithotripsy accelerates the spontaneous passage of fragments and reduces episodes of
colic [271].
Complications of ureteroscopy
The overall complication rate after URS is 9-25% [206, 284, 285]. Most complications are minor and do not
require intervention. There is evidence suggesting a risk of post-operative urosepsis of up to 5% [286, 287].
Ureteral avulsion and strictures are rare (< 1%). Previous perforations, pre-operative positive urine cultures and
longer operation time are the most important risk factor for complications [255, 288]. Infectious complications
following URS can be minimised using prophylactic antibiotics, limiting stent dwell and procedural time,
identification and treatment of UTI, and planning in patients with large stone burden and multiple comorbidities
[289].
High intrarenal pressure (IRP) predisposes to URS complications, and measures should be used to reduce IRP.
Currently there are no accurate ways to measure intra-operative IRP [290].
3.4.6.1 Summary of evidence and recommendations for retrograde URS, RIRS and antegrade ureteroscopy
In uncomplicated URS, a post-procedure stent need not be inserted. 1a
In URS, pre-stenting has been shown to improve outcomes only for renal stones. 2a
An α-blocker can reduce stent-related symptoms and colic episodes. 1a
The most effective lithotripsy system for flexible ureteroscopy is the Ho:YAG laser. 2a
Pneumatic and US systems can be used with high disintegration efficacy in rigid URS. 2a
Percutaneous antegrade removal of proximal ureter stones, or laparoscopic ureterolithotomy are 1b
feasible alternatives to retrograde ureteroscopy, in selected cases.
Pre-treatment of patients undergoing URS with an α-blocker one week prior to the procedure reduces 1a
the need for active dilatation and increases the stone free rate.

Use holmium:yttrium-aluminium-garnet (Ho:YAG) laser lithotripsy for (flexible) ureteroscopy Strong
(URS).
Perform stone extraction only under direct endoscopic visualisation of the stone. Strong
Do not insert a stent in uncomplicated cases. Strong
Offer medical expulsive therapy for patients suffering from stent-related symptoms and after Strong
Ho:YAG laser lithotripsy to facilitate the passage of fragments.
Use percutaneous antegrade removal of ureteral stones as an alternative when shock Strong
wave lithotripsy (SWL) is not indicated or has failed, and when the upper urinary tract is not
amenable to retrograde URS.
Use flexible URS in cases where percutaneous nephrolithotomy or SWL are not an option Strong
(even for stones > 2 cm). However, in this case there is a higher risk that a follow-up
procedure and placement of a ureteral stent may be needed.
3.4.7 Percutaneous nephrolithotomy

Percutaneous nephrolithotomy remains the standard procedure for large renal calculi. Different rigid and flexible
endoscopes are available, and the selection is mainly based on the surgeon’s own reference. Standard access
tracts are 24-30 F. Smaller access sheaths, < 18 F, were initially introduced for paediatric use, but are now
increasingly utilised in the adult population [291, 292].

Contraindications
Patients receiving anti-coagulant therapy must be monitored carefully pre- and post-operatively. Anti-coagulant
therapy must be discontinued before PNL [293].
Other important contraindications include:

• untreated UTI;
• tumour in the presumptive access tract area;
• potential malignant kidney tumour;
• pregnancy (Section 3.4.14.1).
Best clinical practice

Intracorporeal lithotripsy
Several methods for intracorporeal lithotripsy during PNL are available. Ultrasonic and pneumatic systems
are most commonly used for rigid nephroscopy, whilst laser is increasingly used for miniaturised instruments
[294]. Flexible endoscopes also require laser lithotripsy to maintain tip deflection, with the Ho:YAG laser having
become the standard.
Pre-operative imaging
Pre-procedural imaging evaluations are summarised in Section 3.3.1. In particular, US or CT of the kidney
and the surrounding structures can provide information regarding interposed organs within the planned
percutaneous path (e.g., spleen, liver, large bowel, pleura, and lung).
Positioning of the patient

Both prone and supine positions are equally safe, although the supine position confers some advantages,
it depends on appropriate equipment being available to position the patient correctly, for example, X-ray
devices and an operating table. A meta-analysis including 12 studies and a total of 1,290 patients treated,
showed a similar SFR but a lower operative time for supine PNL [295]. Prone position offers more options for
puncture and is therefore preferred for upper pole or multiple accesses [296, 297]. On the other hand, supine
position allows simultaneous retrograde access to the collecting system, using flexible ureteroscope [298]. The
combination of PNL and RIRS may be a good alternative for the treatment of complex renal stones compared
to standard PNL; however, the existing evidence is of low quality [295].
Puncture
Although fluoroscopy is the most common intra-operative imaging method, the (additional) use of US reduces
radiation exposure [299-301]. Pre-operative CT or intra-operative US allows identification of the tissue between
the skin and kidney and lowers the incidence of visceral injury. The calyceal puncture may be done under direct
visualisation using simultaneous flexible URS [300, 302, 303].
Dilatation
Dilatation of the percutaneous access tract can be achieved using a metallic telescope, single (one-shot
or serial) dilators, or a balloon dilatator. During PNL, safety and effectiveness are similar for different tract
dilatation methods [304]. Although there are papers demonstrating that single step dilation is equally effective
as other methods and that US only can be used for the dilatation, the difference in outcomes is most likely
related to surgeon experience rather than to the technology used [304, 305]. A meta-analysis on the most
commonly used tract dilation methods suggested that one-step dilation would allow for a shorter operative
time and reduced complication rate, including haemoglobin loss and transfusion rate [306].
Choice of instruments
Several meta-analyses on mPNL (12-22 F) vs. standard PNL (> 22 F) have identified that both techniques
allow for a similar SFR. Patients treated with mPNL had reduced blood loss and transfusion rates, as well as
shorter hospital stays, without a significant difference in overall complication rates [292, 307-309]. However, it
is important to note that the level of evidence was downgraded due to heterogeneity of data related to tract
sizes used and types of stones treated. There is some evidence for using suction during PNL to reduce IRP and
increase SFR [310].
Nephrostomy and stents

The decision on whether, or not, to place a nephrostomy tube at the conclusion of the PNL procedure depends
on several factors, including:
• presence of residual stones;
• likelihood of a second-look procedure;

• significant intra-operative blood loss;
• urine extravasation;
• ureteral obstruction;
• potential persistent bacteriuria due to infected stones;
• solitary kidney;
• bleeding diathesis;
• planned percutaneous chemolitholysis.
Small-bore nephrostomies seem to have advantages in terms of post-operative pain [292, 311, 312]. Tubeless
PNL is performed without a nephrostomy tube and is associated with reduced post-operative pain and hospital
stay [313]. When neither a nephrostomy tube nor a ureteral stent is introduced, the procedure is known as
totally tubeless PNL [314]. In uncomplicated cases, the latter procedure results in a shorter hospital stay, with
no disadvantages reported [315].
Complications of percutaneous nephrolithotomy

A systematic review of almost 12,000 patients shows the incidence of complications associated with PNL;
fever 10.8%, transfusion 7%, thoracic complication 1.5%, sepsis 0.5%, organ injury 0.4%, embolisation 0.4%,
urinoma 0.2%, and death 0.05% [316].
Peri-operative fever can occur, even with a sterile pre-operative urinary culture and peri-operative
antibiotic prophylaxis, because the renal stones themselves may be a source of infection. The evidence
demonstrates that a stone culture or urine culture taken directly from the renal pelvis is more predictive of post-
operative systemic inflammatory response syndrome (SIRS) or sepsis. Whenever possible a urine culture from
the renal pelvis and/or stone culture should be taken at time of percutaneous cystolithotripsy [317].
Intra-operative renal stone or renal pelvic urine culture may be more indicative of the causative
organism for sepsis; therefore, helping to select the most suitable post-operative antibiotics [317-319]. Intra-
operative irrigation pressure < 30 mmHg and unobstructed post-operative urinary drainage may be important
factors in preventing post-operative sepsis [320]. Bleeding after PNL may be treated by briefly clamping the
nephrostomy tube. Super-selective embolic occlusion of the arterial branch may become necessary in the case
of severe bleeding. The use of tranexamic acid seems to reduce bleeding complications and transfusion rate of
PNL; however, more evidence is needed before it can be introduced in routine clinical practice [321, 322].
To reduce post-operative pain after PNL, a peripheral nerve block can be performed at the intercostal nerve,
paravertebral region, erector spinae or quadratus lumborum. Such a block may significantly reduce the need
for post-operative opioid analgesics [323].
High IRP predisposes to PNL complications, and measures should be taken to reduce IRP. Currently there are
no accurate ways to measure IRP [290].
3.4.7.1 Summary of evidence and recommendations for endourology techniques for renal stone removal
Imaging of the kidney with US or CT can provide information regarding inter-positioned organs within 1a
the planned percutaneous path (e.g., spleen, liver, large bowel, pleura, and lung).
Both prone and supine positions are equally safe with equivalent SFR. 1a
Percutaneous nephrolithotomy performed with small instruments tends to be associated with 1a
significantly lower blood loss, but the duration of procedure tended to be significantly longer. There are
no significant differences in SFR or any other complications.
In uncomplicated cases, a totally tubeless PNL results in a shorter hospital stay, with no increase in 1a
complication rate.
Peri-operative use of tranexamic acid may reduce bleeding complications and transfusion rates. 1a
Urine culture taken directly from the renal pelvis or a stone culture are more predictive of post-PNL 1a
sepsis than a pre-operative midstream urine culture.

Perform pre-procedural imaging, including contrast medium where possible or retrograde Strong
study when starting the procedure, to assess stone comprehensiveness and anatomy of the
collecting system to ensure safe access to the renal stone.
Perform a tubeless (without nephrostomy tube) or totally tubeless (without nephrostomy Strong
tube and ureteral stent) percutaneous nephrolithotomy (PNL) procedure, in uncomplicated
cases.
Take a stone culture or urine culture directly from the renal pelvis at time of PNL, if possible. Strong
3.4.8 General recommendations and precautions for stone removal

3.4.8.1 Antibiotic therapy
Urinary tract infections should always be treated if stone removal is planned. In patients with clinically
significant infection and obstruction, drainage should be performed for several days before starting stone
removal. A urine culture or urinary microscopy should be performed before treatment [324].
Peri-operative antibiotic prophylaxis

For prevention of infection following URS and percutaneous stone removal, no clear-cut evidence exists [289,
325]. In a review of a large database of patients undergoing PNL, it was found that in patients with negative
baseline urine culture, antibiotic prophylaxis significantly reduced the rate of post-operative fever and other
complications [326]. Single dose administration prior to ureteroscopy was found to be sufficient [327]. Based
on a meta-analysis by Yu et al., an extended course of pre-operative prophylactic antibiotics prior to PNL
compared to single dose before anaesthesia significantly reduced post-operative sepsis and fever [318]. In an
RCT including only moderate to high-risk of infection patients (patients with pre-operative stents/nephrostomy
or positive urine culture), a seven-day course of pre-operative antibiotics reduced the risk of post-PNL sepsis
threefold in comparison to a two-day course. In studies that did not specify the risk of the patient population,
a single dose of antibiotic prophylaxis administered at induction was equivalent to an extended pre-operative
course [328]. In contrast to this, a prolonged course of post-operative antibiotics was not superior to a single
dose pre-operatively [318, 329].
As national and regional antibiotic resistance patterns can differ significantly, the choice of antibiotic
prophylaxis should be tailored to institutional or regional antimicrobial susceptibility [330].

Obtain a urine culture or perform urinary microscopy before any treatment is planned. Strong
Exclude or treat urinary tract infections prior to stone removal. Strong
Offer peri-operative antibiotic prophylaxis to all patients undergoing endourological Strong
treatment.
3.4.8.2 Antithrombotic therapy and stone treatment

Patients with a bleeding disorder, or receiving antithrombotic therapy, should be referred to an internist for
appropriate therapeutic measures before deciding on stone management [331-335]. In patients with an
uncorrected bleeding disorder, the following are at elevated risk of haemorrhage or perinephric haematoma
(PNH) (high-risk procedures):
• SWL (hazard ratio of PNH up to 4.2 during anti-coagulant/anti-platelet medication [336-338]);
• PNL;
• percutaneous nephrostomy;
• laparoscopic surgery;
• open surgery [331].
Shock wave lithotripsy is feasible and safe after correction of the underlying coagulopathy [339-343]. In the
case of an uncorrected bleeding disorder or continued antithrombotic therapy, URS, in contrast to SWL
and PNL, might offer an alternative approach since it is associated with less morbidity [344-346]. Despite
appropriate cessation of anti-platelet agents, following standardised protocols, prolonged haematuria in
tube drainage after PNL has been reported [347]. Only data on flexible URS are available which support the
superiority of URS in the treatment of proximal ureteral stones [348, 349]. Although URS is safe in patients with
bleeding disorders or anticoagulation, an individualised patient-approach is necessary [346].

Table 3.9: Risk stratification for bleeding [333-335, 350]
Low-risk bleeding procedures • Cystoscopy
• Flexible cystoscopy
• Ureteral catheterisation
• Extraction of ureteral stent
• Ureteroscopy
High-risk bleeding procedures • Shock wave lithotripsy
• Percutaneous nephrostomy
• Percutaneous nephrolithotomy
Table 3.10: Suggested strategy for antithrombotic therapy in stone removal [333-335]
(In collaboration with a cardiologist/internist weigh the risks and benefits of discontinuation of therapy, vs.
delaying elective surgical procedures).
Medication/Agent Bleeding risk of Risk of thromboembolism

planned procedure Low risk Intermediate risk High risk
Warfarin Low-risk procedure May be continued Bridging therapy Bridging therapy
Dabigatran High-risk procedure May be temporarily Bridging therapy Bridging therapy
Rivaroxaban discontinued at
Apixaban appropriate interval.
Bridging therapy
is strongly
recommended.
Aspirin Low-risk procedure Continue Continue Elective surgery:
postpone.
Non-deferrable
surgery: continue.
High-risk procedure Discontinue Elective surgery: Elective surgery:
postpone. postpone.
Non-deferrable Non-deferrable
surgery: continue, if surgery: continue.
it is possible.
Thienopyridine Low-risk procedure Discontinue Continue Elective surgery:
agents (P2Y12 five days before postpone.
receptor inhibitors) intervention. Non-deferrable
Resume within surgery: continue.
24-72 hours with a
loading dose.
High-risk procedure Discontinue Elective surgery: Elective surgery:
five days before postpone. postpone.
intervention and Non-deferrable Non-deferrable
resume within 24-72 surgery: discontinue surgery: discontinue
hours with a loading five days before five days before
dose. procedure and procedure and
resume within 24-72 resume within 24-72
hours with a loading hours, with a loading
dose. dose.
Bridging therapy Bridging therapy
-glycoprotein IIb/IIIa -glycoprotein IIb/IIIa
inhibitors if aspirin is inhibitors.
discontinued.

3.4.8.2.1 Summary of evidence and recommendations for antithrombotic therapy and stone treatment
Active surveillance is indicated in patients at high risk for thrombotic complications in the presence of 4
an asymptomatic calyceal stone.
The temporary discontinuation, or bridging of antithrombotic therapy in high-risk patients, should be 3
discussed with the internist.
Retrograde (flexible) URS stone removal is associated with less morbidity in patients when antithrombotic 2a
therapy cannot be discontinued.

Offer active surveillance to patients at high risk of thrombotic complications in the presence Weak
of an asymptomatic calyceal stone.
Decide on temporary discontinuation, or bridging of antithrombotic therapy in high-risk Strong
patients, in consultation with the internist.
Retrograde (flexible) ureteroscopy is the preferred intervention if stone removal is essential Strong
and antithrombotic therapy cannot be discontinued since it is associated with less morbidity.
3.4.8.3 Obesity
A high BMI can pose a higher anaesthetic risk and a lower success rate after SWL and PNL and may influence
the choice of treatment [351].
3.4.8.4 Stone composition

Stones composed of brushite, calcium oxalate monohydrate, or cystine are particularly hard, as well as
homogeneous stones with a high density on NCCT [46, 352]. Percutaneous nephrolithotomy or RIRS and URS
are alternatives for removal of large SWL-resistant stones.

Consider the stone composition before deciding on the method of removal, based on Strong
patient history, former stone analysis of the patient or Hounsfield unit on unenhanced
computed tomography.
Attempt to dissolve radiolucent stones. Strong
3.4.8.5 Contraindications of procedures

Contraindications of extracorporeal SWL
There are several contraindications to the use of extracorporeal SWL, including:
• pregnancy, due to the potential effects on the foetus [353];
• bleeding disorders, which should be compensated for at least 24 hours before and 48 hours after
treatment [354];
• uncontrolled UTIs;
• severe skeletal malformations and severe obesity, which prevent targeting of the stone;
• arterial aneurysm in the vicinity of the stone [355];
• anatomical obstruction distal to the stone.
Contraindications of URS
Apart from general problems, for example with general anaesthesia or untreated UTIs, URS can be performed
in all patients without any specific contraindications.
Contraindications of PNL
Patients receiving anti-coagulant therapy must be monitored carefully pre- and post-operatively. Anti-coagulant
therapy must be discontinued before PNL [346]. Other important contraindications include:
• untreated UTI;
• tumour in the presumptive access tract area;
• potential malignant kidney tumour;
• pregnancy (Section 3.4.14.1).

General contraindication for endourological procedures
Endourological interventions do not adversely affect renal function although care must be taken in those with
poor pre-operative renal function, diabetes and hypertension [356]. However, a meta-analysis, based on low-
quality evidence, suggests that patients with impaired renal function and stone disease, may in fact benefit
from the procedure to preserve or increase their renal function [357].
3.4.9 Specific stone management of ureteral stones

3.4.9.1 Conservative treatment/observation
There are only limited data regarding spontaneous stone passage according to stone size [358]. It is estimated
that 95% of stones up to 4 mm pass within 40 days [206].
Based on an analysis of available evidence, an exact cut-off size for stones that are likely to pass
spontaneously cannot be provided [206].
Spontaneous stone passage was reported for 49% of upper ureteral stones, 58% of mid ureteral stones and
68% of distal ureteral stones. Considering stone size almost 75% of stones < 5 mm and 62% of stones > 5
mm passed spontaneously, with an average time to stone expulsion about 17 days (range 6-29 days) [359].
The Panel is aware of the fact that spontaneous stone expulsion decreases with increasing stone size and that
there are differences between individual patients.
According to a number of RCT based meta-analysis sexual intercourse has been reported to be
beneficial in facilitating stone expulsion in men with distal ureteral stones and be comparable to MET [360-362].
3.4.9.2 Pharmacological treatment, medical expulsive therapy

Medical expulsive therapy should only be used in informed patients if active stone removal is not indicated.
Treatment should be discontinued if complications develop (infection, refractory pain, deterioration of renal
function). In case of known uric acid stones in the distal ureter, a combination of alkalinisation with tamsulosin
can increase the frequency of spontaneous passage. For details see Sections 3.4.3 and 3.4.4.
3.4.9.3 Indications for active removal of ureteral stones

Indications for active removal of ureteral stones are [206, 358, 363]:
• stones with a low likelihood of spontaneous passage;
• persistent pain despite adequate analgesic medication;
• persistent obstruction;
• renal insufficiency (renal failure, bilateral obstruction, or single kidney).
3.4.9.4 Selection of procedure for active removal of ureteral stones

Overall, SFRs after URS or SWL for ureteral stones are comparable. However, larger stones achieve earlier stone-
free status with URS.
A large multi-center non-inferiority trial compared URS to ESWL for ureteral stones. When excluding patients that
had spontaneously passed their stone prior to treatment, ESWL could not be considered non-inferior to URS
with only 12% of patients needing further intervention after URS in comparison to 26% in the SWL arm [364]. In
the current endourological era, the complication rate and morbidity of URS has been significantly reduced [365].
It has been demonstrated that URS is a safe option in obese patients (BMI > 30 kg/m2) with comparable SFRs
and complication rates. However, in morbidly obese patients (BMI > 35 kg/m2) the overall complication rates
double [366].
The Panel performed a systematic review to assess the benefits and harms of URS compared to SWL [367].
Compared with SWL, URS was associated with a significantly greater SFR of up to four weeks, but the difference
was not significant at three months in the included studies. Ureteroscopy was associated with fewer retreatments
and need for secondary procedures, but with a higher need for adjunctive procedures, greater complication
rates and longer hospital stay. Counterbalancing for URS’s higher SFRs, SWL is associated with lower morbidity.
Success rates and complications of URS are not impacted by previous unsuccessful SWL [368]. Clavien-Dindo
grade complications were, if reported, less frequent in patients treated with SWL [369].
Bleeding disorder
Ureteroscopy can be performed in patients with bleeding disorders, with a moderate increase in complications
(see also Section 3.4.8.2) [346].

3.4.9.4.1 S
ummary of evidence and recommendations for selection of procedure for active removal of ureteral
stones
Observation is feasible in informed patients who develop no complications (infection, refractory pain, 1a
deterioration of renal function).
Medical expulsive therapy seems to be efficacious for treating patients with ureteral stones who are 1a
amenable to conservative management. The greatest benefit might be among those with > 5 mm
(distal) stones.
Compared with SWL, URS was associated with significantly greater SFRs up to four weeks, but the 1a
difference was not significant at three months in the included studies.
Ureteroscopy was associated with fewer retreatments and need for secondary procedures, but with a 1a
higher need for adjunctive procedures, greater complication rates and longer hospital stay.
In the case of severe obesity, URS is a more promising therapeutic option than SWL. 2b

If active removal is not indicated (Section 3.4.9.3) in patients with newly diagnosed small* Strong
ureteral stones, observe patient initially with periodic evaluation.
Offer α-blockers as medical expulsive therapy as one of the treatment options for (distal) Strong
ureteral stones > 5 mm.
Inform patients that ureteroscopy (URS) has a better chance of achieving stone-free status Strong
with a single procedure.
Inform patients that URS has higher complication rates when compared to shock wave Strong
lithotripsy.
Use URS as first-line therapy for ureteral (and renal) stones in cases of severe obesity. Strong
*See stratification data [206].
Figure 3.1: Treatment algorithm for ureteral stones (if active stone removal is indicated)
Proximal ureteral stone
1. URS (ante- or retrograde)

> 10 mm
2. SWL
< 10 mm SWL or URS
Distal ureteral stone
1. URS
> 10 mm
2. SWL
< 10 mm SWL or URS
SWL = shock wave lithotripsy; URS = Ureteroscopy.

3.4.10 Specific stone management of renal stones
The natural history of small, non-obstructing asymptomatic calculi is not well defined, and the risk of
progression is unclear. There is still no consensus on the follow-up duration, timing, and type of intervention.
Treatment options are chemolysis or active stone removal.
3.4.10.1 Conservative treatment (observation)

Observation of renal stones, especially in calyces, depends on their natural history (Section 3.4.10.3). The
recommendations provided are not supported by high-level literature [370]. There is a prospective trial
supporting annual observation for asymptomatic inferior calyceal stones, < 10 mm. In case stone growth is
detected, the follow-up interval should be lowered. Intervention is advised for growing stones > 5 mm [371].
In a systematic review of patients with asymptomatic renal stones on active surveillance spontaneous stone
passage rates varied from 3-29%, symptom development from 7-77%, stone growth from 5-66%, surgical
intervention from 7-26% [370], respective risk of symptomatic episodes ranged from 0-59.4% [372].
3.4.10.2 Pharmacological treatment of renal stones

Dissolution of stones through pharmacological treatment is an option for uric acid stones only, but information on
the composition of the stone will need to guide the type of treatment selected. See sections 3.4.4. and 3.4.8.4.
3.4.10.3 Indications for active stone removal of renal stones

Indications for the removal of renal stones, include:
• stone growth;
• stones in high-risk patients for stone formation;
• obstruction caused by stones;
• infection;
• symptomatic stones (e.g., pain or haematuria) [373];
• stones > 15 mm;
• stones < 15 mm if observation is not the option of choice;
• patient preference;
• comorbidity;
• social situation of the patient (e.g., profession or travelling);
• choice of treatment.
The risk of a symptomatic episode or need for intervention in patients with asymptomatic renal stones
seems to be ~10-25% per year, with a cumulative five-year event probability of 48.5% [371, 372, 374, 375].
A prospective RCT with more than two years clinical follow-up reported no significant difference between
SWL and observation when comparing asymptomatic calyceal stones < 15 mm in terms of SFR, symptoms,
requirement for additional treatment, quality of life (QoL), renal function, or hospital admission [376]. Although
some have recommended prophylaxis for these stones to prevent renal colic, haematuria, infection, or stone
growth, conflicting data have been reported [375, 377, 378]. In a follow-up period of almost five years after
SWL, two series have demonstrated that up to 25% of patients with small residual fragments needed treatment
[215, 379]. Although the question of whether calyceal stones should be treated is still unanswered, stone
growth, de novo obstruction, associated infection, and acute and/or chronic pain are indications for treatment
[373, 380, 381]. There is some evidence that external physical vibration lithecbole (EPVL) after SWL and RIRS
results in higher SFRs [203].
3.4.10.4 Selection of procedure for active removal of renal stones

For general recommendations and precautions see Section 3.4.8.
3.4.10.4.1 Stones in renal pelvis or upper/middle calyces

Shock wave lithotripsy, PNL and RIRS are available treatment modalities for renal calculi. While PNL efficacy
is hardly affected by stone size, the SFRs after SWL or URS are inversely proportional to stone size [364, 382-
388]. Although multiple treatments or sessions may be needed SWL achieves good SFRs for stones up to 20
mm, except for those at the lower pole [384, 389, 390]. Endourology is considered an alternative because of
the reduced need for repeated procedures and consequently a shorter time until stone-free status is achieved.
For stones > 10 mm, mini-PNL (mPNL) achieves a higher SFR than RIRS or ESWL, but carries a higher risk
of bleeding and is associated with a longer hospital stay; however, there is a high degree of heterogeneity
among the included studies [386, 388]. Stones > 20 mm should be treated primarily by PNL, because SWL
often requires multiple treatments, and is associated with an increased risk of ureteral obstruction (colic or
steinstrasse) with a need for adjunctive procedures (Figure 3.2) [204]. Retrograde renal surgery cannot be
recommended as first-line treatment for stones > 20 mm in uncomplicated cases as SFRs decrease, and

staged procedures will be required [391-393]. However, it may be a first-line option in patients where PNL is
not an option or contraindicated or in selected patients [394]. The combination of PNL and RIRS may be a
good alternative for the treatment of complex renal stones compared to standard PNL; however, the level of the
existing evidence is low [295].
3.4.10.4.2 Stones in the lower renal pole

The stone clearance rate after SWL seems to be lower for stones in the inferior calyx than for other intra-renal
locations. Although the disintegration efficacy of SWL is not limited compared to other locations, the fragments
often remain in the calyx and cause recurrent stone formation. The reported SFR of SWL for lower pole calculi
is 25-95%. The preferential use of endoscopic procedures is supported by some current reports, even for
stones < 1 cm [204, 382, 383, 385, 389, 393, 395-407].
The following can impair successful stone treatment by SWL [397, 408-413]:
• steep infundibular-pelvic angle;
• long calyx;
• long skin-to-stone distance;
• narrow infundibulum;
• shock wave-resistant stones (calcium oxalate monohydrate, brushite, or cystine).
Further anatomical parameters cannot yet be established. Supportive measures such as inversion, vibration or
hydration may facilitate stone clearance (See 3.4.5 ESWL) [201, 203, 414]. If there are negative predictors for
SWL, PNL and RIRS might be reasonable alternatives, even for smaller calculi [395]. Retrograde renal surgery
seems to have comparable efficacy to SWL [204, 383, 389, 415]. Recent clinical experience has suggested
a higher SFR of RIRS compared to SWL, but at the expense of greater invasiveness. Depending on operator
skills, stones up to 3 cm can be treated by RIRS [237, 416-418]. However, staged procedures are frequently
required. Although mPNL has the highest success rate for the treatment of lower pole stones up to 2 cm, it
comes at the expense of a higher complication rate and longer hospital stay [388].
In complex stone cases, open or laparoscopic approaches are possible alternatives although they
are infrequently used.
3.4.10.5 Summary of evidence and recommendations for the management of renal stones
It is still debatable whether renal stones should be treated, or whether annual follow-up is sufficient for 4
asymptomatic calyceal stones that have remained stable for six months.
Although the question of whether asymptomatic calyceal stones should be treated is still unanswered, 3
stone growth, de novo obstruction, associated infection, and acute and/or chronic pain are indications
for treatment.
Percutaneous nephrolithotomy is indicated in renal stones > 2 cm as primary option. 1a

Follow-up periodically in cases where renal stones are not treated (initially after six months Strong
then yearly evaluating symptoms and stone status either by ultrasound or kidney-ureter
bladder radiography. Use computed tomography (CT) when intervention is required.
Offer active treatment for renal stones in case of stone growth, de novo obstruction, Weak
associated infection, and acute and/or chronic pain.
Evaluate stone composition before deciding on the method of removal, based on patient Strong
history, former stone analysis of the patient or Hounsfield unit (HU) on unenhanced CT.
Stones with density > 1,000 HU (and with high homogeneity) on non-contrast-enhanced CT
are less likely to be disintegrated by shock wave lithotripsy.
Perform percutaneous nephrolithotomy (PNL) as first-line treatment of larger stones > 2 cm. Strong
Treat larger stones (> 2 cm) with flexible ureteroscopy or shock wave lithotripsy (SWL), in Strong
cases where PNL is not an option. However, in such instances there is a higher risk that a
follow-up procedure and placement of a ureteral stent may be needed.
Perform PNL or retrograde intrarenal surgery for the lower pole, even for stones > 1 cm, as Strong
the efficacy of SWL is limited (depending on favourable and unfavourable factors for SWL).

Figure 3.2: Treatment algorithm for renal stones (if/when active treatment is indicated)
Kidney stone
(all but lower pole stone 10-20 mm)
1. PNL
> 20 mm
2. RIRS or SWL
10-20 mm SWL or Endourology*
1. SWL or RIRS
< 10 mm
2. PNL
Lower pole stone

(> 20 mm and < 10 mm: as above)
No SWL or Endourology*
Unfavourable
10-20 mm factors for SWL
(see section 3.4.5)
1. Endourology*
Yes 2. SWL
*The term ‘Endourology’ encompasses all PNL and URS interventions.

PNL = percutaneous nephrolithotomy; RIRS = retrograde intrarenal surgery; SWL = shock wave lithotripsy;
URS = ureteroscopy.
3.4.11 Laparoscopy and open surgery

Advances in SWL and endourological surgery (URS and PNL) have significantly decreased the indications
for open or laparoscopic stone surgery [419-424]. There is a consensus that most complex stones, including
partial and complete staghorn stones, should be approached primarily with PNL. Additionally, a combined
approach with PNL and RIRS may also be an appropriate alternative. However, if percutaneous approaches are
not likely to be successful, or if multiple endourological approaches have been performed unsuccessfully; open
or laparoscopic surgery may be a valid treatment option [425-431].
Few studies have reported laparoscopic stone removal. These procedures are usually reserved for
special cases. When expertise is available, laparoscopic ureterolithotomy can be performed for large proximal
ureteral stones as an alternative to URS or SWL [432, 433]. These more invasive procedures have yielded high
SFRs and lower auxiliary procedure rates [230, 241, 434]. A recent systematic review showed no difference in
the post-operative phase for stented or unstented laparoscopic ureterolithotomy [434].
Laparoscopic pyelolithotomy could be offered for solitary stones > 2cm located in renal pelvis as
an alternative to PNL [435]. In addition, in selected cases with an extrarenal and dilated pelvis, retroperitoneal
laparoscopic pyelolithotomy (RLP) can be considered as an alternative management of staghorn calculi [436].
A few studies with limited numbers of patients have reported using robotic surgery in the treatment
of urinary stones [437]. Open surgery should be considered as the last treatment option, after all other
possibilities have been explored.
Studies on laparoscopy should be interpreted with caution due to their poor design and low quality
of evidence.

3.4.11.1 Recommendation for laparoscopy and open surgery

Offer laparoscopic or open surgical stone removal in rare cases in which shock wave Strong
lithotripsy, retrograde or antegrade ureteroscopy and percutaneous nephrolithotomy fail, or
are unlikely to be successful.
3.4.12 Steinstrasse
Steinstrasse is an accumulation of stone fragments or stone gravel in the ureter and may interfere with
the passage of urine [438]. Steinstrasse occurs in 4-7% cases of SWL [225], and the major factor in the
development of steinstrasse formation is stone size [439].
A major problem of steinstrasse is ureteral obstruction, which may be silent in up to 23% of cases. A MA
including eight RCTs (n = 876) suggested a benefit of stenting before SWL in terms of steinstrasse formation,
but did not result in a benefit on SFRs or less auxiliary treatments [154]. When steinstrasse is asymptomatic,
conservative treatment is an initial option. Medical expulsion therapy increases stone expulsion and reduces
the need for endoscopic intervention [440, 441]. Ureteroscopy and SWL are effective in treatment of
steinstrasse [227, 442]. In the event of UTI or fever, the urinary system should be decompressed, preferably by
percutaneous nephrostomy [125, 129].
3.4.12.1 Summary of evidence and recommendations for steinstrasse
Medical expulsion therapy increases the stone expulsion rate of steinstrasse. 1b
Ureteroscopy is effective for the treatment of steinstrasse. 3
Only low-level evidence is available, supporting SWL or URS for the treatment of steinstrasse. 4

Treat steinstrasse associated with urinary tract infection (UTI)/fever preferably with Weak
percutaneous nephrostomy.
Treat steinstrasse when large stone fragments are present with shock wave lithotripsy or Weak
ureteroscopy (in absence of signs of UTI).
3.4.13 Management of patients with residual stones

Following initial treatment with SWL, URS or PNL, residual fragments may remain and require additional
intervention [372, 379, 443-445]. Most of the studies indicate that initial imaging is performed on the first day
or the first week after treatment. However, false positive results from dust or residual fragments, that will pass
spontaneously without causing any stone-related event, might lead to over-treatment. Therefore, imaging
at four weeks seems most appropriate [446-448]. Compared to US, KUB and IVU, NCCT scan has a higher
sensitivity to detect small residual fragments after definitive treatment of ureteral or kidney stones [449, 450].
However, more than half of the patients with a residual fragment on NCCT images may not experience a stone-
related event [451].
It is clear that NCCT has the highest sensitivity to detect residual fragments; however, this must be balanced
against the increased detection of clinically insignificant fragments and the exposure to ionising radiation when
compared with KUB and US. In the absence of high-level supporting evidence, the timing of follow-up imaging
studies and need for secondary intervention is left to the discretion of the treating physician. Recurrence risk in
patients with residual fragments after treatment of infection stones is higher than for other stones [452]. For all
stone compositions, 21-59% of patients with residual stones required treatment within five years. Fragments >
5 mm are more likely than smaller ones to require intervention [215, 372, 445, 453, 454]. There is evidence that
fragments > 2 mm are more likely to grow, although this is not associated with increased re-intervention rates
at one year follow up [443].

3.4.13.1 Summary of evidence and recommendation for management of patients with residual stones
To detect residual fragments after SWL, URS or PNL, deferred imaging is more appropriate than 3
immediate imaging post intervention.

Perform imaging after shock wave lithotripsy, ureteroscopy or percutaneous antegrade Strong
ureteroscopy to determine presence of residual fragments.
3.4.14 Management of specific patient groups

3.4.14.1 Management of urinary stones and related problems during pregnancy
Clinical management of a pregnant urolithiasis patient is complex and demands close collaboration between
patient, radiologist, obstetrician, and urologist [70]. For diagnostic imaging see Section 3.3.1. Patients with
urolithiasis may be at increased risk of developing adverse maternal or neonatal outcomes [455].
If spontaneous passage does not occur, or if complications develop (e.g., intractable symptoms,
severe hydronephrosis, spontaneous renal fornix rupture [456] or induction of premature labour), placement
of a ureteral stent or a percutaneous nephrostomy tube is necessary as it is more effective than conservative
treatment for symptom relief [127, 457, 458].
Unfortunately, these temporising therapies are often associated with poor tolerance, and they require multiple
exchanges during pregnancy, due to the potential for rapid encrustation [459].
Ureteroscopy has become a reasonable alternative in these situations [448, 460]. When compared to temporary
ureteral JJ stenting until after delivery, ureteroscopy resulted in reduced need for stent exchanges, less irritative
lower urinary tract symptoms and better patient satisfaction [461, 462].
Non-urgent ureteroscopy in pregnant women is best performed during the second trimester, by an experienced
urologist. Counselling of the patient should include access to neonatal and obstetric services [78].
Although feasible, percutaneous removal of renal stones during pregnancy remains an individual decision and
should be performed only in experienced centres [463]. Pregnancy remains an absolute contraindication for
SWL.
3.4.14.1.1 Summary of evidence and recommendation for the management of urinary stones and related
problems during pregnancy
Stent insertion seems to be more effective than conservative treatment in the management of 1a
symptomatic moderate-to-severe hydronephrosis during pregnancy.
Ureteroscopy is a reasonable alternative to avoid long-term stenting/drainage. 1b
There is a higher tendency for stent encrustation during pregnancy. 3

Treat all uncomplicated cases of urolithiasis in pregnancy conservatively (except when there Strong
are clinical indications for intervention).
3.4.14.2 Management of stones in patients with urinary diversion

Aetiology
Patients with urinary diversion are at high risk for stone formation in the renal collecting system and ureter
or in the conduit or continent reservoir [464, 465]. Metabolic factors (hypercalciuria, hyperoxaluria and
hypocitraturia), infection with urease-producing bacteria, foreign bodies, mucus secretion, and urinary stasis
are responsible for stone formation [466] (section 3.1.3). One study has shown that the risk for recurrent upper
tract stones in patients with urinary diversion subjected to PNL was 63% at five years [467].

Management
Smaller upper-tract stones can be treated effectively with SWL [234, 468]. In the majority of cases, endourological
techniques are necessary to achieve stone-free status [232]. In individuals with long, tortuous conduits or with
invisible ureter orifices, a retrograde endoscopic approach might be difficult or impossible [469].
For stones in the conduit, a trans-stomal approach can be used to remove all stone material (along with the
foreign body) using standard techniques, including intracorporeal lithotripsy and flexible endoscopes. Trans-
stomal manipulations in continent urinary diversion must be performed carefully to avoid disturbance of the
continence mechanism [470].
Before considering any percutaneous approach in these cases, CT should be undertaken to assess
the presence of overlying bowel, which could make this approach unsafe [471], and if present, an open surgical
approach should be considered.
Prevention
Recurrence risk is high in these patients [467]. Metabolic evaluation and close follow-up are necessary
to obtain the risk parameters for effective long-term prevention. Preventive measures include medical
management of metabolic abnormalities, appropriate therapy of urinary infections, and hyperdiuresis or regular
irrigation of continent reservoirs [472].
3.4.14.2.1 Summary of evidence and recommendation for the management of stones in patients with urinary
diversion
The choice of access depends on the feasibility of orifice identification in the conduit or bowel 4
reservoir. Whenever a retrograde approach is impossible, percutaneous access with antegrade
ureteroscopy is the alternative.

Perform percutaneous lithotomy to remove large renal stones in patients with urinary Strong
diversion, as well as for ureteral stones that cannot be accessed via a retrograde approach,
or that are not amenable to shock wave lithotripsy.
3.4.14.3 Management of stones in patients with neurogenic bladder

Aetiology, clinical presentation and diagnosis
Patients with neurogenic bladder develop urinary calculi because of additional risk factors such as bacteriuria,
hydronephrosis, VUR, renal scarring and lower urinary tract reconstruction [473]. The most common causes are
urinary stasis and infection (Section 3.1.3). Indwelling catheters and surgical interposition of bowel segments for
treatment of bladder dysfunction both facilitate UTI. Although calculi can form at any level of the urinary tract, they
occur more frequently in the bladder; especially if bladder augmentation has been performed [474, 475].
Diagnosis of stones may be difficult and delayed in the absence of clinical symptoms due to
sensory impairment and vesico-urethral dysfunction. Difficulties in self-catheterisation should lead to suspicion
of bladder calculi. Imaging studies are needed (US, CT) to confirm the clinical diagnosis prior to surgical
intervention.
Management
Management of calculi in patients with neurogenic bladder is similar to that described in Section 3.3.3. In
myelomeningocele patients, latex allergy is common; therefore, appropriate measures need to be taken
regardless of the treatment [476]. Any surgery in these patients must be performed under general anaesthesia
because of the impossibility of using spinal anaesthesia. Bone deformities often complicate positioning on
the operating table [477]. The risk of stone formation after augmentation cystoplasty in immobile patients with
sensory impairment can be significantly reduced by irrigation protocols [472].
For efficient long-term stone prevention in patients with neurogenic bladder, correction of the
metabolic disorder, appropriate infection control, and restoration of normal storing/voiding function of the
bladder are needed.

3.4.14.3.1 Summary of evidence and recommendation for the management of stones in patients with
neurogenic bladder
Patients undergoing urinary diversion and/or suffering from neurogenic bladder dysfunction are at risk 3
for recurrent stone formation.
In myelomeningocele patients, latex allergy is common. 2

Take appropriate measures regardless of the treatment provided since in myelomeningocele Strong
patients latex allergy is common.
3.4.14.4 Management of stones in patients with transplanted kidneys

Stones in transplanted kidneys can either be transplanted or present de novo allograft stones. Usually they are
detected by routine US examination, followed by NCCT in cases of unclear diagnosis [478].
Aetiology
Transplant patients depend on their solitary kidney for renal function. Impairment causing urinary stasis/
obstruction therefore requires immediate intervention or drainage of the transplanted kidney. Stones in kidney
allografts have an incidence of 1% [479]. Risk factors for de novo stone formation in these patients are multi-fold:
• Immunosuppression increases the infection risk, resulting in recurrent UTIs.
• Hyper-filtration, excessively alkaline urine, renal tubular acidosis (RTA), and increased serum calcium
caused by persistent tertiary hyperparathyroidism [480] are biochemical risk factors.
Management
Selecting the appropriate technique for stone removal in a transplanted kidney is difficult, although
management principles are similar to those applied in other single renal units [481-483]. Additional factors such
as transplant function, coagulative status, and anatomical obstacles due to the iliacal position of the organ,
directly influence the surgical strategy.
For large or ureteral stones, careful percutaneous access and subsequent antegrade endoscopy
are more favourable. The introduction of small flexible ureteroscopes and the holmium laser has made URS a
valid treatment option for transplant calculi; however, one must be aware of potential injury to adjacent organs
[482, 484, 485]. Retrograde access to transplanted kidneys is difficult due to the anterior location of the ureteral
anastomosis, and ureteral tortuosity [486-488].Treatment of donor stones may be needed pre-transplant and
increases the pool available for renal transplants. Post-transplant stone disease may also need treatment to
maintain the allograft function. A systematic review evaluating the outcomes of pre- vs. post-transplant URS
demonstrated a 100% SFR with an overall 7.5% complication rate, compared to SFR of 60-100% with an
overall complication rate of 12.9% for post-transplant URS; most complications were Clavien 1 [489].
3.4.14.4.1 Summary of evidence and recommendation for the management of stones in patients with
transplanted kidneys
Conservative treatment for small asymptomatic stones is only possible under close surveillance and in 3
absolutely compliant patients.
Shock wave lithotripsy for small calyceal stones is an option with minimal risk of complication, but 4
localisation of the stone can be challenging and SFRs are poor.

Offer patients with transplanted kidneys, any of the contemporary management options, Weak
including shock wave lithotripsy, flexible ureteroscopy and percutaneous nephrolithotomy.

3.4.14.5 Special problems in stone removal
Table 3.11: Special problems in stone removal
Calyceal diverticulum • SWL, PNL [490] (if possible) or RIRS [490, 491].
stones • Can also be removed using laparoscopic retroperitoneal surgery [492, 493].
• Patients may become asymptomatic due to stone disintegration (SWL),
whilst well-disintegrated stone material remains in the original position due
to narrow calyceal neck.
Horseshoe kidneys • Can be treated in line with the options described above [494].
• Passage of fragments after SWL might be poor.
• Acceptable SFRs (up to 76%) with low major complication rates (2.4%)
can be achieved with flexible ureteroscopy [495-497].
Stones in pelvic kidneys • SWL, RIRS, PNL or laparoscopic surgery [498].
Stones formed in a • Each stone must be considered and treated individually.
continent reservoir
Patients with obstruction of • When outflow abnormality requires correction, stones can be removed by
the UPJ PNL together with percutaneous endopyelotomy or open/laparoscopic
reconstructive surgery.
• URS together with endopyelotomy with Ho:YAG laser.
• Incision with an Acucise® balloon catheter might be considered, provided
the stones can be prevented from falling into the pelvic-ureteral incision
[499-502].
• Open surgery with correction of the UPJ obstruction (pyeloplasty) and
stone removal is a feasible option [503].
3.4.15 Management of stones in children

The true incidence of nephrolithiasis in children remains unclear due to the global lack of large epidemiological
studies. Data derived from nation-wide epidemiological studies, studies performed in different counties
worldwide [504] and large-scale databases [505, 506] indicate that the incidence and prevalence of paediatric
urinary stone disease has increased over the last few decades. Although boys are most commonly affected in the
first decade of life [507] the greatest increase in incidence has been seen in older female adolescences [504].
Stone composition is similar in children as in adults, with a predominance of calcium oxalate stones.
Compared to historical data, metabolic abnormalities responsible for stone formation are less commonly
identified in children nowadays [508-510]. Hypocitraturia, low urine volume and hypercalciuria predominate
[87, 508-510]. Age may affect the predominant metabolic abnormality with hypercalciuria and hypocitraturia
being the most common disorder present in children < 10 and > 10 years old, respectively [510]. Genetic or
systemic diseases (e.g., cystinuria or nephrocalcinosis) contributing to stone formation are relatively frequent in
children accounting for less than 17% of the identifying causes [508, 511]. The role of diet remains unclear in
children, although there is some evidence that children are drinking less water and taking greater daily amounts
of sodium than is recommended [512-514].
For diagnostic procedures see Section 3.3.3.2, for acute decompression see Section 3.4.2. and for metabolic
evaluation see Chapter 4.
3.4.15.1 Clinical presentation

Children with urinary stones can be asymptomatic or present with non-specific symptoms that necessitate a
high index of suspicion for proper diagnosis. Symptoms are age-dependent with infants presenting with crying,
irritability and vomiting in 40% of cases [515] while in older children flank pain, micro or gross haematuria and
recurrent UTIs are more common [516].
3.4.15.2 Conservative management

There is a lack of evidence on conservative management of paediatric stones with evidence for ureteric calculi
coming from the placebo arms of medical expulsive trials, while evidence for renal stones comes from small
cohort studies, either on primary stones [517, 518] or residual fragments remained after SWL, RIRS or PNL
[519]. Expectant management for single, asymptomatic lower-pole renal stones could be the initial approach
with increased odds of stone passage, especially in patients with non-struvite, non-cystine stones < 7 mm,
with no anatomic abnormalities [517]. Intervention may be needed for stones located elsewhere independently
of their size [517-519].

3.4.15.3 Medical expulsive therapy in children
There are limited studies on MET as off-label expulsive therapy for children with stones which show conflicting
outcomes. A systematic review of six placebo-controlled studies showed that α-blockers might increase SFR
of distal ureteric stones (RR: 1.34, 95% CI: 1.16 - 1.54) [520]. A recent MA of MET for distal ureteric stones
including nine RCTs found that α-blockers could significantly increase the rate of stone expulsion, reduce
the stone expulsion time, decrease pain episodes and analgesia demand, but had a higher incidence of side
effects [521].
3.4.15.4 Extracorporeal shock wave lithotripsy

Shock wave lithotripsy is still the first-line treatment for most ureteral stones in children. However, it is less
likely to be successful for stones > 10 mm in diameter, impacted stones, calcium oxalate monohydrate or
cystine stones, or for stones in children with unfavourable anatomy and in whom localisation is difficult [522].
Studies on ESWL in children suggest an overall SFR of 70-90%, retreatment rate of 4-50% and
need for auxiliary procedures in 4-12.5% of cases [523-527]. A MA of fourteen studies reporting on 1,842
paediatric patients treated with SWL found significantly higher SFR for stones < 10 mm than for stones
> 10 mm and higher retreatment rates as the stone size increased [522]. For best clinical practice see
Section 3.4.5. A recent MA on slow SWL vs. rapid SWL for renal stones revealed very low-quality evidence
about the effects of SWL on SFRs, serious adverse events or complications of treatment and secondary
procedures for residual fragments [520]. Shock wave lithotripsy is well tolerated; however, good treatment
outcomes are more likely to require the administration of general anaesthesia to children. With improvements
in modern (second and third generation) lithotripters, successful treatment using intravenous sedation, patient-
controlled analgesia or no medication at all has been increasingly performed in a select population of older,
co-operative children [528].
Based on the results of a recent MA which compared SWL to dissolution therapy for intra-renal stones,
and SWL to ureteroscopy with holmium laser or pneumatic lithotripsy for renal and distal ureteric
stones, no firm conclusions can be drawn about the effects of SWL on SFR, serious adverse events
or complications of treatment and secondary procedures for residual fragments [520]. When SWL was
compared to mPNL for lower pole renal stones 1-2 cm in size SWL resulted in lower SFRs (RR: 0.88, 95%
CI: 0.80 - 0.97; moderate-quality evidence) and higher rates of secondary procedures (RR: 2.50, 95%
CI: 1.01 - 6.20; low-quality evidence); however, SWL showed less severe adverse events (RR: 0.13, 95%
CI: 0.02 - 0.98; low quality evidence) [529].
3.4.15.5 Endourological procedures

Rigid/semi-rigid ureteroscopy
In recent years ureteroscopy is increasingly used in children with ureteral stones [530]. Ureteroscopy proved
to be effective with SFR of 81-98% [531-533], retreatment rates of 6.3%-10% [534] and complication rates of
1.9-23% [531-533, 535]. Similar to adults, routine stenting is not necessary before URS. Pre-stenting may
facilitate URS, increase SFR and decrease complication rates [536, 537].
Flexible ureteroscopy/retrograde intrarenal surgery

Retrograde intra-renal surgery with flexible ureteroscopes (FURS) has become an efficacious treatment
modality for paediatric renal stones. Recent studies report SFRs of 76-100%, retreatment rates of 0-19% and
complication rates of 0-28% [538-541]. Younger age, cystine composition [542], large stone diameter [541] and
lack of pre-stenting predispose to FURS failure in children [536]. A large global study across eight centres show
a SFR of 75.5%; although, complications were minor, they were higher in patients < 5 years of age [543].
Although high-level evidence is lacking to support a strong recommendation [520], FURS may be a
particularly effective treatment option for lower calyceal stones in the presence of unfavourable factors for SWL
[533, 539, 544].
For large and complex kidney stones RIRS has a significantly lower SFR compared to PNL
(71% vs. 95%), but is associated with less radiation exposure, lower complication rates and a shorter
hospital stay [545]. Similarly, retrospectively data indicate that RIRS may achieve lower SFRs compared
to minor micropercutaneous surgery in favour of shorter operative time, shorter fluoroscopy time, and less
hospitalisation time [546, 547]. A recently published MA confirmed these results [548].
Percutaneous nephrolithotomy
Indications for PNL in children are similar to those in adults, and include renal stones > 2 cm, or smaller stones
resistant to SWL and ureteroscopic treatment. Reported SFRs with paediatric PNL are 71.4-95% after a single
session [545-547, 549, 550] with an overall complication rate of 20% [551]. High degree of hydronephrosis,
increased number of tracts and operative time [552] and large tract size [550, 553-555] are associated with

increased blood loss. Child age [554] and stone burden [550] predispose to the use of larger instruments
during PNL in children. Miniaturisation of equipment increases the opportunity to perform tubeless PNL in
appropriately selected children, which can reduce the length of hospital stay and post-operative pain [556,
557]. A recent systematic review on the role of mPNL showed an initial and overall SFR of 87.9% and 97%
respectively, with no conversions to standard PNL, and a complication rate of 19%, with a mean transfusion
rate of 3.3% [543].
Concerns have been raised regarding possible adverse effects of PNL on the renal parenchyma
of the developing child. However, focal damage is only reported in 5% of cases [558]. Using pre- and post-
PNL dimercaptosuccinic acid (DMSA) scans, Cicekbilek et al. demonstrated that PNL tracts between 12-24
Charrière in size did not cause significant harm to paediatric kidneys [549].
3.4.15.6 Open and laparoscopic/robot-assisted stone surgery

With the advances in ESWL, PNL and RIRS, very few cases of paediatric urolithiasis require open surgery. Data
extracted from the National Inpatient Sample (NIS) databases for 2001-2014 showed that in the USA incisional
procedures (mainly nephrolithotomy, pyelolithotomy and ureterotomy) were performed in 2.6% of hospitalised
patients (52% aged 15-17 years) who required surgical intervention for urinary stones [559]. Laparoscopy
for the management of paediatric renal and ureteric stones is a safe and effective procedure when specific
indications are followed. Stone free rates of 100% were reported when laparoscopic pyelolithotomy was
applied for a > 1cm single stone located in an extra-renal pelvis [560], or when laparoscopic ureterolithotomy
was applied to impacted ureteric stones > 1.5 cm, or to ureteric stones that were refractory to SWL or URS
[561]. There are extremely limited data available on efficacy and complications of robot-assisted laparoscopic
management of paediatric urolithiasis [562].
3.4.15.7 Special considerations on recurrence prevention

All paediatric stone formers need metabolic evaluation and recurrence prevention with respect to the detected
stone type. Children are in the high-risk group for stone recurrence (See Chapter 4).
3.4.15.8 Summary of evidence and recommendations for the management of stones in children
In children, MET could increase the rate of stone expulsion, reduce the stone expulsion time, and 1b
decrease pain episodes/analgesia demand, but it has a higher incidence of side effects.
In children, the indications for SWL, URS and PNL are similar to those in adults. 1b
Children with renal stones of a diameter up to 20 mm (~300 mm2) are ideal candidates for SWL. 1b
Ureteroscopy has become the treatment of choice for larger distal ureteral stones in children. 1a
In children, the indications for PNL are similar to those in adults. 1a
MiniPNL is safe and effective in children. 1b

Offer children with single ureteral stones less than 10 mm shock wave lithotripsy (SWL) if Strong
localisation is possible or ureteroscopy as first-line option.
Ureteroscopy is a feasible alternative for ureteral stones not amenable to SWL. Strong
Offer children with renal stones with a diameter of up to 20 mm (~300 mm2) SWL. Strong
Offer children with renal pelvic or calyceal stones with a diameter > 20 mm (~300 mm2) Strong
percutaneous nephrolithotomy.
Retrograde renal surgery is a feasible alternative for renal stones smaller than 20 mm in all Weak
locations.
3.5 Radiation exposure and protection during endourology

The diagnosis and treatment of nephrolithiasis is associated with high levels of ionising radiation exposure to
patients [563, 564]. Currently, there are no studies estimating the lifetime radiation exposure of stone formers
or the subsequent risk of malignancy development. The radiation exposure of endourologists has been
extensively studied. Still, there are no studies assessing the risk of radiation induced malignancies in urologists
or operating theatre staff members [565-567].
Current evidence from atomic bomb patients [568, 569], retrospective epidemiological data on medical
exposure [570, 571] and modelling studies [572, 573] suggest an age and dose dependent risk of secondary
malignancy from ionising radiation.

The International Commission on Radiological Protection (ICRP) recommends a maximum annual occupational
exposure of 50mSv [574]. However, the risk of radiation induced malignancy follows a stochastic model having
no known safe threshold of exposure. Taking this into consideration as well as the length of a urologists career
the upper limit of 50mSv is still highly concerning.
Table 3.12 shows the EAU Urolithiasis guidelines panel recommended protection methods to reduce radiation
exposure to patients, surgical, anaesthesiologic and nursing staff.
Table 3.12 Radiation protection measures

• Limit studies or intervention involving radiation exposure to those that are strictly medically necessary.
• Implement a patient electronic record of medical imaging.
• Make use of imaging studies with lower radiation doses (US, KUB, digital tomosynthesis, low-dose and
ultra-low dose CT scan).
• Create and follow a precise radiation exposure protection protocol in your department.
• Act in accordance with the as low as reasonably achievable (ALARA) principle.
• Measure and report fluoroscopy time to the operative surgeon (use dosimeters and perform monthly
calculations).
• Technical measures to reduce radiation exposure include:
Reducing fluoroscopy time;
Limiting time adjacent to patient;
Using low-dose radiation;
Irradiating only to observe motion;
Intra-operative use of pulsed fluoroscopy;
Reduced fluoroscopy pulse rate;
Collimated fields;
Avoid digital image acquisition and rely on last image hold and instant replay technology.
• Use radiation protection instruments (chest, pelvic and thyroid shields, lead or lead-free gloves,
protective glasses, lead protection under the operating table between the x-ray source and the surgeon).
• The radiation protection instruments must be cared for appropriately as any damage decreases
effectiveness and increases exposure risk. They should be monitored and measured regularly to ensure
integrity.
• Proper surgeon and operating room setup should be observed (follow the inverse square law, use the
X-ray source underneath the patient’s body, decrease the X-ray source to patient distance, reduce
magnification, avoid field overlap by not turning the C-arm in extreme angles, operate in the standing
rather than the seated position).
Availability of fluoroscopy is mandatory for endourological procedures. There is an increasing interest on

fluoroless and fluoroscopy-free operations in urology. Several RCTs have been published showing a good
outcome in means of stone free and complication rates [183, 300, 575-577]. These trials have been limited to
non-complex cases and they were not sufficiently powered to show non-inferiority of fluoroscopy in PNL [300,
565] or superiority of ultrasound in URS [249, 250].
4. METABOLIC EVALUATION AND RECURRENCE

PREVENTION
4.1 General metabolic considerations for patient work-up
4.1.1 Evaluation of patient risk
After stone passage, every patient should be assigned to a low- or high-risk group for stone formation (Figure 4.1).
For correct classification, two items are mandatory:
• reliable stone analysis by infrared spectroscopy or X-ray diffraction;
• basic analysis (Section 3.3.2).

Only high-risk stone formers require specific metabolic evaluation. Stone type is the deciding factor for further
diagnostic tests. The different stone types include:
• calcium oxalate;
• calcium phosphate;
• uric acid;
• ammonium urate;
• struvite (and infection stones);
• cystine;
• xanthine;
• 2,8-Dihydroxyadenine;
• drug stones;
• stones of unknown composition.
Figure 4.1: Assignment of patients to low- or high-risk groups for stone formation
STONE
Stone analysis Stone analysis

known unknown
Investigating a patient
Basic evaluation
with unknown
(Section 3.3.2.3)
composition (Table 3.1)
Low-risk Risk factors High-risk

no yes
stone former Present stone former
Specific metabolic
evaluation
General preventive Stone specific

measures recurrence prevention
4.1.2 Urine sampling

Specific metabolic evaluation requires collection of two consecutive 24-hour urine samples [69, 578, 579].
The collecting bottles should be prepared 1 g thymol per litre in or stored at < 8°C during collection to reduce
bacterial proliferation [69]. Pre-analytical errors can be minimised by carrying out urinalysis immediately after
collection. Alternatively, boric acid (10 g powder per urine container) can also be used, but this prevents
the correct determination of pH [69]. The collecting method should be chosen in close cooperation with the
laboratory. A pH < 5.5 in a 24-hour urine indicates hyper acidic urine (acidic arrest) [580-582]. During therapy
urine pH should be assessed during collection of freshly voided urine at different times throughout the day
using sensitive pH-dipsticks or a pH-meter [27, 69, 583]. A urine pH on 24-hr collection > 6.2 is suspicious for

distal RTA [584]. A consensus statement from Gambaro et al., stated that RTA is suspected if 24-hr urine pH is
> 6.2 and fasting second morning spot urine pH is > 5.8 [585].
Spot urine samples are an alternative method of sampling, particularly when 24-hour’s urine collection is
difficult, for example, in non-toilet trained children [586]. Spot urine studies normally link the excretion rates
to creatinine [587], but these are of limited use because the results may vary with collection time and patients’
sex, body weight and age.
4.1.3 Timing of specific metabolic work-up

For the initial specific metabolic work-up, the patient should stay on a self-determined diet under normal daily
conditions and should ideally be stone free for at least twenty days [588]. Follow-up studies are necessary
in patients taking medication for recurrence prevention [589]. The first follow-up 24-hour urine measurement
is suggested eight to twelve weeks after starting pharmacological prevention of stone recurrence. This
enables drug dosage to be adjusted if urinary risk factors have not normalised, with further 24-hour urine
measurements, if necessary. Once urinary parameters have been normalised, it is sufficient to perform 24-hour
urine evaluation every twelve months. On this issue the Panel realise that there is only very limited published
evidence.
4.1.4 Reference ranges of laboratory values

Tables 4.1-4.4 provide the internationally accepted reference ranges for the different laboratory values in serum
and urine.
Table 4.1: Normal laboratory values for blood parameters in adults [27, 589]
Blood parameter Reference range
Creatinine 50-100 μmol/L
Sodium 135-145 mmol/L
Potassium 3.5-5.5 mmol/L
Calcium 2.0-2.5 mmol/L (total calcium)
1.12-1.32 mmol/L (ionised calcium)
Uric acid 119-380 μmol/L
Chloride 98-112 mmol/L
Phosphate 0.81-1.29 mmol/L
Blood gas analysis pH 7.35-7.45
pO2 80-90 mmHg
pCO2 35-45 mmHg
HCO3 22-26 mmol/L
BE BE ± 2 mmol/L
BE = base excess (loss of buffer base to neutralise acid); HCO3 = bicarbonate; pCO2 = partial pressure of
carbon dioxide; pO2 = partial pressure of oxygen.
4.1.5 Risk indices and additional diagnostic tools

Several risk indices have been developed to describe the crystallisation risk for calcium oxalate or calcium
phosphate in urine [590-593]. However, clinical validation of these risk indices for recurrence prediction or
therapy improvement is ongoing.
Table 4.2: Laboratory values for urinary parameters in adults

Urinary Parameters Reference ranges and limits for medical attention
pH Consistently fasting morning spot urine pH > 5.8 and
> 6.2 in 24-hr collection (suspicious of renal tubular
acidosis) [584, 585]
Consistently > 7.0 (suspicious of infection)
Consistently < 5.5 in morning urine and in 24-hr
collection (suspicious of acidic arrest) [580, 594]
Specific weight Specific weight > 1.010
Creatinine 7-13 mmol/day (females), 13-18 mmol/day (males)
Calcium > 5.0 mmol/day (see Fig. 4.2)
> 8.0 mmol/day (see Fig. 4.2)

Oxalate > 0.5 mmol/day (suspicious of enteric hyperoxaluria)
>1.0 mmol/day (suspicious of primary hyperoxaluria)
Uric acid > 4.0 mmol/day (females), 5 mmol/day (males)
Citrate < male < 1.7 mmol/day, female < 1.9 mmol/day
Magnesium < 3.0 mmol/day
Inorganic phosphate > 35 mmol/day
Ammonium > 50 mmol/day
Cystine > 0.8 mmol/day
Table 4.3: Normal values for spot urine samples: creatinine ratios (solute/creatinine) in children [595]
Parameter/Patient age Ratio of solute to creatinine Units
Calcium mol/mol mg/mg
< 12 months < 2.0 0.81
1-3 years < 1.5 0.53
1-5 years < 1.1 0.39
5-7 years < 0.8 0.28
> 7 years < 0.6 0.21
Oxalate mol/mol mg/mg
0-6 months < 325-360 288-260
7-24 months < 132-174 110-139
2-5 years < 98-101 80
5-14 years < 70-82 60-65
> 16 years < 40 32
Citrate mol/mol g/g
0-5 years > 0.25 0.42
> 5 years > 0.15 0.25
Magnesium* mol/mol g/g
All age groups > 0.63 > 0.13
Uric acid
> 2 years < 0.56 mg/dL (33 μmol/L) per GFR (ratio x plasma creatinine)
* There is low-level evidence regarding the importance of magnesium.
Table 4.4: Solute excretion in 24-hour urine samples in children [596, 597]*
Calcium/24 Citrate/24 hour Cystine/24 hour Oxalate/24 hour Urate/24 hour
hour
All age groups Boys Girls < 10 years > 10 years All age < 1 year 1-5 years > 5 years
groups
< 0.1 mmol/kg/ > 1.9 mmol/ > 1.6 mmol/ < 55 μmol/ < 200 μmol/ < 0.5 mmol/ < 70 μmol/ < 65 mμmol/ < 55 μmol/
24 h 1.73 m2/24 h 1.73 m2/24 h 1.73 m2/24 h 1.73 m2/24 h 1.73 m2/24 h kg/24 h kg/24 h kg/24 h
< 4 mg/kg/24 h > 365 mg/ > 310 mg/ < 13 mg/ < 48 mg/ < 45 mg / < 13 mg/ < 11 mg/ < 9.3 mg/
1.73 m2/24 h 1.73 m2/24 h 1.73 m2/24 h 1.73 m2/24 h 1.73 m2/24 h kg/24 h kg/24 h kg/24 h
* 24 h urine parameters are diet and gender dependent and may vary geographically.
4.2 General considerations for recurrence prevention

All stone formers, independent of their individual risk, should follow the preventive measures in Table 4.5.
The main focus is normalisation of dietary habits and lifestyle risks. Stone formers at high risk need specific
prophylaxis for recurrence, which is usually pharmacological treatment based on stone analysis and urinary risk
profile.
Table 4.5: General preventive measures

Fluid intake (drinking advice) Fluid amount: 2.5-3.0 L/day
Fluid amount: 2.5-3.0 L/day
Water is the preferred fluid
Diuresis: 2.0-2.5 L/day
Specific weight of urine: < 1,010 g/day

Nutritional advice for a balanced diet Balanced diet*
Rich in vegetables and fibre
Normal calcium content: 1-1.2 g/day
Limited NaCl content: 4-5 g/day
Limited animal protein content: 0.8-1.0 g/kg/day
Lifestyle advice to normalise general risk factors BMI: Retain a normal BMI level
Adequate physical activity
Balancing of excessive fluid loss
Reduce the intake of alcohol containing fluids
Reduce the intake of sodas and calorie-containing
fluids
Caution: Protein requirements are age dependent; therefore, protein restriction in childhood should be handled
carefully.
* Avoid excessive consumption of vitamin supplements.
4.2.1 Fluid intake

An inverse relationship between high fluid intake and stone formation has been repeatedly demonstrated [596-
600]. The beneficial effect of fruit juices is mainly determined by the presence of citrate or bicarbonate [601].
Citrus fruit juices seem to protect against stone disease either by increasing urinary citrate levels or by having
an alkalinising effect on it [602]. However, if potassium is present, both pH and citrate are increased [603,
604]. One large moderate quality RCT randomly assigned men with more than one past renal stone of any
type and soft drink consumption of at least 160 mL/day to reduced soft drink intake or no treatment. Although
the intervention significantly reduced the risk for symptomatic recurrent stones (RR: 0.83; CI: 0.71-0.98), the
level of evidence for this outcome is low because results were from only one trial [605]. An analysis on the
3 Channing’s cohorts (194,095 participants) over a median follow-up of more than eight years has shown
that consumption of sugar-sweetened soda and punch is associated with a higher risk of stone formation,
whereas consumption of coffee, tea, beer, wine, and orange juice is associated with a lower risk [606], whereas
consumption of tea and coffee does not seem to increase the risk of stones disease [607]. However, the intake
of fluids should be considered within a holistic approach to health. Some of them contain calories or alcohol
that may be detrimental to health. Therefore, water should be the preferred fluid.
4.2.2 Diet
A common-sense approach to diet should be taken, that is, a mixed, balanced diet with contributions from all
food groups, without any excesses [597, 608, 609]. Sufficient calcium intake is needed, especially in vegetarian
and vegan diets [610].
Fruit, vegetables and fibre: Fruit and vegetable intake should be encouraged because of the beneficial effects
of fibre, although the role of the latter in preventing stone recurrences is debatable [611-614]. The alkaline
content of a vegetarian diet also increases urinary pH. In addition, fruit and vegetables have a high water
content and can significantly contribute to fluid intake.
Oxalate: Excessive intake of oxalate-rich products should be limited or avoided to prevent high oxalate load
[615], particularly in patients who have high oxalate excretion.
Vitamin C: Although vitamin C is a precursor of oxalate, its role as a risk factor in calcium oxalate stone
formation remains controversial [616]. However, it seems wise to advise calcium oxalate stone formers to avoid
excessive intake.
Animal protein: Animal protein should not be consumed in excess [617, 618] and limited to 0.8-1.0 g/kg body
weight. Excessive consumption of animal protein has several effects that favour stone formation, including
hypocitraturia, low urine pH, hyperoxaluria and hyperuricosuria.
Calcium intake: Calcium should not be restricted, unless there are strong reasons for doing so, due to the
inverse relationship between dietary calcium and stone formation [612, 619]. The daily requirement for calcium
is 1,000 to 1,200 mg [27]. Calcium supplements are not recommended except in enteric hyperoxaluria, when
additional calcium should be taken with meals to bind intestinal oxalate [597, 615, 617, 620]. Older adults who
do not have a history of renal stones but who take calcium supplements should ensure adequate fluid intake
since it may prevent increases in urine calcium concentration, and thereby reduce or eliminate any increased
risk of renal stones formation associated with calcium supplement use [621].

Sodium: Daily sodium (NaCl) intake should not exceed 3-5 g [27]. High intake adversely affects urine
composition:
• calcium excretion is increased by reduced tubular re-absorption;
• urinary citrate is reduced due to loss of bicarbonate;
• increased risk of sodium urate crystal formation.
Calcium stone formation can be reduced by restricting sodium and animal protein [617, 618]. A positive
correlation between sodium consumption and risk of first-time stone formation has been confirmed only in
women [619]. There have been no prospective clinical trials on the role of sodium restriction as an independent
variable in reducing the risk of stone formation.
Urate: Intake of purine-rich food should be restricted in patients with hyperuricosuric calcium oxalate [622, 623]
and uric acid stones. Intake should not exceed 500 mg/day [27].
4.2.3 Lifestyle
Lifestyle factors may influence the risk of stone formation, for example, those causing obesity [624], diabetes
mellitus [625], and metabolic syndrome [626].
4.2.4 Summary of evidence and recommendation for recurrence prevention
Increasing water intake reduces the risk of stone recurrence. 1a

Advise patients that a generous fluid intake is to be maintained, allowing for a 24-hour urine Strong
volume > 2.5 L.
4.3 Stone-specific metabolic evaluation and pharmacological recurrence prevention

4.3.1 Introduction
Pharmacological treatment is necessary in patients at high risk for stone formation or for associated systemic
conditions. The ideal drug should halt stone formation, have no side effects, and be easy to administer. Each of
these aspects is important to achieve good compliance. Table 4.6 highlights the most important characteristics
of commonly used medication.
Table 4.6: Pharmacological substances used for stone prevention - characteristics, specifics and dosage
Agent Rationale Dose Specifics and side Stone type Ref
effects
Alkaline citrates Alkalinisation 5-12 g/d Daily dose for Calcium oxalate [627-632]
(14-36 mmol/d) alkalinisation depends Uric acid
Hypocitraturia on urine pH. Cystine
Children:
Inhibition of 0.1-0.15 g/kg/d
calcium oxalate
crystallisation
Allopurinol Hyperuricosuria 100-300 mg/d 100 mg in isolated Calcium oxalate [597,
hyperuricosuria. Uric acid 633-636]
Hyperuricaemia Children: Renal insufficiency Ammonium urate
1-3 mg/kg/d demands dose 2,8-Dihydroxyadenine
correction.
Contraindicated in
acute gout, pregnancy,
and breastfeeding.
Allergies from trivial
to very severe forms,
xanthine stone
formation.
Calcium Enteric Up to 2,000 mg/d Intake 30 min before Calcium oxalate [617, 619,
hyperoxaluria depending on meals. 620, 637]
oxalate excretion

Captopril Cystinuria 75-150 mg Second-line option Cystine [638, 639]
Active decrease in case of significant
of urinary cystine side effects of
levels tiopronin.
Febuxostat Hyperuricosuria 80-120 mg/d Contraindicated in Calcium oxalate [640, 641
acute gout, pregnancy Uric acid
Hyperuricaemia and breastfeeding.
Xanthine stone
formation.
L-Methionine Acidification 600-1,500 mg/d Hypercalciuria, bone Infection stones [627, 642]
demineralisation, Ammonium urate
systemic acidosis. Calcium phosphate
No long-term therapy.
Magnesium Isolated 200-400 mg/d Renal insufficiency Calcium oxalate [643, 644]
hypomagnesiuria demands dose (Low level
Children: correction. of
Enteric 6 mg/kg/d Diarrhoea, chronic evidence)
hyperoxaluria alkali losses,
hypocitraturia.
Sodium bicarbonate Alkalinisation 4.5 g/d N/A Calcium oxalate [645]
Hypocitraturia Uric acid, Cystine
Pyridoxine Primary Initial dose Sensory peripheral Calcium oxalate [646]
hyperoxaluria 5 mg/kg/d neuropathy.
Max. 20 mg/kg/d
Thiazide Hypercalciuria 25-50 mg/d Risk for hypotonic Calcium oxalate [623,
(Hydrochlorothiazide*) blood pressure, Calcium phosphate 627-636,
Children: diabetes, 638-656]
0.5-1 mg/kg/d hyperuricaemia,
hypokalaemia,
followed by
intracellular acidosis
and hypocitraturia.
Tiopronin Cystinuria Initial dose Risk for tachyphylaxis Cystine [657-660]
Active decrease 800 mg/d and proteinuria.
of urinary cystine Avg. 2,000 mg/d**
levels
Children:
Initial dose in
patients > 20kg is
15 mg/kg/day.
Avoid dosages
> 50mg/kg/day
* P atients on hydrochlorothiazides should be advised to get their skin checked on a regular basis as they have
a higher risk of developing a non-melanoma skin cancer (NMSC) and some forms of melanoma. In patients
with history of skin cancer the indication for the intake of hydrochlorothiazides should be thoroughly reviewed
[661-663].
** No information is available on maximum dose and patients may be initiated on a very low dose if they have had
previously had reactions to tiopronin or penicillamine. For all patients, dosage should be titrated according to
frequency of stone episodes, side effects and renal function under expert supervision with close monitoring.
4.4 Calcium oxalate stones

The criteria for identification of calcium oxalate stone formers with high recurrence risk are listed in section
3.1.3.
4.4.1 Diagnosis
Blood analysis requires measurement of creatinine, sodium, potassium, chloride, ionised calcium (or total
calcium + albumin), phosphate, uric acid; and, in the case of increased calcium levels, parathyroid hormone
(PTH) and vitamin D. Urinalysis requires measurement of urine volume, urine pH profile, specific weight,
calcium, oxalate, uric acid, citrate, sodium and magnesium. Figure 4.2 summarises the diagnostic steps for
calcium oxalate stones.

46
Calcium oxalate stone
No
Persistent
metabolic
Hypercalciuria Hypocitraturia Hyperoxaluria Hyperuricosuria Hypomagnesuria low urine
abnor-
volume
mality
Normo- Diarrheal
Meta- Reduced
calcemia Hypo- Idio- states
bolic Poor intestinal
Normo- Hyper- + kalemia pathic Hyper- Normou-
Acidosis Dietary Enteric Primary dietary absorption
calcemia calcemia Meta- uricemia ricemia
intake (chronic
bolic
diarrhea)
acidosis
Idiopathic Primary
Figure 4.2: Diagnostic algorithm for calcium oxalate stones
Low
hyper- Hyperpara- Gout
Calcium
calciuria thyroidism High dietary
intake Small bowel
(commo- Granulo- purine
Distal High intake resection
nest) matous intake
Renal of oxalate- Bariatric Type
Granulo- diseases Myeloprolif
Tubular rich foods Surgery 1, 2, 3
matous Vitamin D erative
Acidosis Excess vit Fat malab-
diseases excess disorders
C intake sorption
(rare) Malignancy Hemolytic
(>5mmol/
Vitamin D Hyper- anaemia
day)
excess thyroidism
UROLITHIASIS - LIMITED UPDATE MARCH 2023

4.4.2 Interpretation of results and aetiology
The most common metabolic abnormalities associated with calcium stone formation are hypercalciuria, which
affects 30-60% of adult stone formers, and hyperoxaluria (26-67%), followed by hyperuricosuria (15-46%),
hypomagnesuria (7-23%), and hypocitraturia (5-29%). However, ranges tend to differ based on ethnicity [664].
• Elevated levels of ionised calcium in serum (or total calcium and albumin) require assessment of intact
PTH to confirm or exclude suspected hyperparathyroidism (HPT).
• Consistently low pH (< 5.5) or 24-hr urine pH < 5.5 may promote co-crystallisation of uric acid and
calcium oxalate.
• Similarly, increased uric acid excretion (> 4 mmol/day in adults or > 12 mg/kg/day in children) can act as a
promoter.
• A pH > 6.2 in a 24-hr urine collection may indicate RTA provided UTI has been excluded. An ammonium
chloride loading test confirms RTA and identifies RTA subtype (Section 4.6.5).
• Hypercalciuria may be associated with normocalcemia (idiopathic hypercalciuria, or granulomatous diseases)
or hypercalcaemia (hyperparathyroidism, granulomatous diseases, vitamin D excess, or malignancy).
• Hypocitraturia (male < 1.7 mmol/d, female < 1.9 mmol/d) may be idiopathic or secondary to metabolic
acidosis or hypokalaemia.
• Oxalate excretion > 0.5 mmol/day in adults confirms hyperoxaluria (see Table 4.3 for the values in children).
oo primary hyperoxaluria (oxalate excretion mostly > 1 mmol/day), appears in three genetically
determined forms;
oo secondary hyperoxaluria (oxalate excretion > 0.5 mmol/day, usually < 1 mmol/day), occurs due to
intestinal hyperabsorption of oxalate or extreme dietary oxalate intake;
oo mild hyperoxaluria (oxalate excretion 0.45-0.85 mmol/day), commonly found in idiopathic calcium
oxalate stone formers.
• Hypomagnesuria (< 3.0 mmol/day) may be related to poor dietary intake or to reduced intestinal absorption
(chronic diarrhoea).

Figure 4.3: Therapeutic algorithm for calcium oxalate stones
Hypomagnesuria*
200-400 mg/d3
Magnesium
< 3 mmol/d
100-300 mg/d4,5
Hyperuricosuria
Hyperuricaemia
Alkaline citrate
> 380 μmol/L
allopurinol
9-12 g/d
plus
and
Hyperuricosuria
Alkaline citrate
bicarbonate
> 4 mmol/d
allopurinol
100 mg/d
1.5 g tid2
9-12 g/d
plus/or
sodium
or
initial 5 mg/kg/d
> 1 mmol/d
20 mg/kg/d
Pyridoxine
(primary)
up to
Calcium oxalate stone
24 h urine collection
Basic evaluation
Hyperoxaluria
depending on oxalate
1,000 to 2,000 mg/d
200-400 mg/d
> 0.5 mmol/d
magnesium*
excretion1
Calcium
(enteric)
and
Hypocitraturia
Female < 1.9

Male < 1.7
9-12 g/d
mmol/d
mmol/d
Alkaline
citrate
initially 25 mg/d
up to 50 mg/d
chlorthalidone
Hydrochloro-
indapamide
thiazide***
8 mmol/d
2.5 mg/d
25 mg/d
Hypercalcuria
Alkaline citrate
5-8 mmol/d**
bicarbonate
1.5 g tid2,4
9-12 g/d
sodium
or
1 Be aware of excess calcium excretion.

2 tid = three times/day (24h).
3 No magnesium therapy for patients with renal insufficiency.
4 There is no evidence that combination therapy (thiazide + citrate) or (thiazide + allopurinol) is superior to
thiazide therapy alone [628, 665].

5 Febuxostat 80 mg/day.
* low evidence (see text)

** Calciuria is a continuous variable and treatment may be adjusted to clinical need even when below the
threshold indicated.
***Patients on hydrochlorothiazides should be advised to get their skin checked on a regular basis as they have
a higher risk of developing a NMSC and some forms of melanoma. In patients with history of skin cancer the
indication for the intake of hydrochlorothiazides should be thoroughly reviewed [661-663].

4.4.3 Specific treatment
General preventive measures are recommended for fluid intake and diet. Hyperoxaluric stone formers should
consume foods with low oxalate content, whereas hyperuricosuric stone formers benefit from daily dietary
reduction of purine. Figure 4.3 summarises the pharmacological treatment of calcium oxalate stones [597, 604,
627-630, 633, 634, 636, 640, 643-645, 649-656, 664, 666-669]. There is only low-level evidence for the efficacy
of preventing stone recurrence based on pre-treatment stone composition examination and biochemistry
measures, or on-treatment biochemistry measures [597].
4.4.4 ummary of evidence and recommendations for pharmacological treatments for patients
S
with specific abnormalities in urine composition (based on 24-hour urine samples)
Thiazide or alkaline citrates or both can reduce stone formation. 1a
Oxalate restriction is beneficial if hyperoxaluria is present. 2b
Alkaline citrates can reduce stone formation in enteric hyperoxaluria. 4
Calcium supplement can reduce stone formation in enteric hyperoxaluria. 2
A diet reduced in fat and oxalate can be beneficial in reducing stone formation. 3
Alkaline citrates and sodium bicarbonate can be used if hypocitraturia is present. 1b
Allopurinol is first-line treatment of hyperuricosuria. 1a
Febuxostat is second-line treatment of hyperuricosuria. 1b
Avoid excessive intake of animal protein in hyperuricosuria. 1b
Restricted intake of salt is beneficial if there is high urinary sodium excretion. 1b

Prescribe thiazide or alkaline citrates or both in case of hypercalciuria*. Strong
Advise oxalate restriction if hyperoxaluria is present. Weak
Offer alkaline citrates in enteric hyperoxaluria. Weak
Offer calcium supplement in enteric hyperoxaluria. Strong
Advise reduced dietary fat and oxalate in enteric hyperoxaluria. Weak
Prescribe alkaline citrates or sodium bicarbonate in case of hypocitraturia. Strong
Prescribe allopurinol in case of hyperuricosuria. Strong
Offer febuxostat as second-line treatment of hyperuricosuria. Strong
Avoid excessive intake of animal protein in hyperuricosuria. Strong
Advise restricted intake of salt if there is high urinary sodium excretion. Strong
*P
atients on hydrochlorothiazides should be advised to get their skin checked on a regular basis as they have
4.5 Calcium phosphate stones [597, 627, 636, 649, 650, 654, 670]
Some calcium phosphate stone formers are at high risk of recurrence. Further information on identifying high-
risk patients is provided in section 3.1.3.
Calcium phosphate mainly appears in two completely different minerals: carbonate apatite and
brushite. Carbonate apatite crystallisation occurs at a pH > 6.8 and may be associated with infection. Brushite
crystallises at an optimum pH of 6.5-6.8 at high urinary concentrations of calcium (> 8 mmol/day) and
phosphate (> 35 mmol/day). Its occurrence is not related to UTI. Possible causes of calcium phosphate stones
include HPT, RTA and UTI; each of which requires different therapy.
4.5.1 Diagnosis
Diagnosis requires blood analysis for: creatinine, sodium, potassium, chloride, ionised calcium (or total calcium
+ albumin), phosphate, and PTH (in the case of increased calcium levels). Urinalysis includes measurement of:
volume, urine pH profile, specific weight, calcium, phosphate and citrate.
4.5.2 Interpretation of results and aetiology

General preventative measures are recommended for fluid intake and diet. The diagnostic and therapeutic
algorithm for calcium phosphate stones is shown in Figure 4.4.

Figure 4.4: Diagnostic and therapeutic algorithm for calcium phosphate stones
Calcium phosphate
stones
Carbonate
apatite Brushite stones
stones
Basic evaluation Basic evaluation
Urinary pH Elevated calcium

Hypercalciuria Exclude HPT Exclude RTA
> 6.5-6.8 Exclude HPT
Hydrochlorothiazide* Hypercalciuria
initially 25 mg/d Exclude RTA Exclude UTI > 8 mmol/d
up to 50 mg/d
Adjust urinary pH Hydrochlorothiazide*

between 5.8 and 6.2 initially 25 mg/d
with L-methionine up to 50 mg/d
200-500 mg chlorthalidone 25 mg/d
3 times daily indapamide 2.5 mg/d
HPT = hyperparathyroidism; RTA = renal tubular acidosis; UTI = urinary tract infection.
* Patients on hydrochlorothiazides should be advised to get their skin checked on a regular basis as they have
4.5.3 Pharmacological therapy [597, 627, 636, 649, 650, 654, 670]
Hyperparathyroidism and RTA are common causes of calcium phosphate stone formation. Most patients
with primary HPT require surgery. Renal tubular acidosis can be corrected pharmacologically including with
bicarbonate or alkaline citrate therapy. If primary HPT and RTA have been excluded, pharmacotherapy for
calcium phosphate calculi depends on effective reduction of urinary calcium levels using thiazides. For infection-
associated calcium phosphate stones, it is important to consider the guidance given for infection stones.
4.5.4 Summary of evidence and recommendation for the management of calcium phosphate
stones
Thiazide is beneficial in case of hypercalciuria. 1a

Prescribe thiazide in case of hypercalciuria. Strong
4.6 Disorders and diseases related to calcium stones

4.6.1 Hyperparathyroidism [671-674]
Primary HPT is responsible for an estimated 5% of all calcium stone formation. Renal stones occur in
approximately 20% of patients with primary HPT. Elevated levels of PTH significantly increase calcium turnover,
leading to hypercalcaemia and hypercalciuria and bone disease. Serum calcium may be mildly elevated and
serum PTH may be within the upper normal limits and, therefore, repeated measurements may be needed;

preferably with the patient fasting. Stones of HPT patients may contain both calcium oxalate and calcium
phosphate. Nephrocalcinosis and CKD may also occur.
If HPT is suspected, neck exploration should be performed to confirm the diagnosis. If surgery is
contraindicated, primary HPT can be treated with cinacalcet.
4.6.2 Granulomatous diseases [675]

Granulomatous diseases, such as sarcoidosis, may be complicated by hypercalcaemia and hypercalciuria
secondary to increased calcitriol production. The latter is independent of PTH control, leading to increased
calcium absorption in the gastrointestinal tract and suppression of PTH. Treatment focuses on the activity of
the granulomatous diseases and may require steroids, hydroxychloroquine or ketoconazole. Treatment should
be reserved for a specialist.
4.6.3 Primary hyperoxaluria [646]

Patients with primary hyperoxaluria (PH) should be referred to specialised centres, as successful management
requires an experienced interdisciplinary team. The main therapeutic aim is to reduce endogenous oxalate
production, which is increased in patients with PH. In approximately one-third of patients with PH type I,
pyridoxine therapy normalises or significantly reduces urinary oxalate excretion. The goal of adequate urine
dilution is achieved by adjusting fluid intake to 3.5-4.0 L/day in adults (children 1.5 L/m2 body surface area) and
following a circadian drinking regimen.
Therapeutic options for preventing calcium oxalate crystallisation include hyperdiuresis, alkaline
citrates, magnesium and Lumasiran, an RNAi agent, which is a new treatment for reducing the synthesis of
oxalate of PH type 1 [676].
Treatment regimens are:

• pyridoxine in PH type I: 5-20 mg/kg/day according to urinary oxalate excretion and patient tolerance;
• alkaline citrate: 9-12 g/day in adults, 0.1-0.15 mq/kg/day in children;
• magnesium: 200-400 mg/day (no magnesium in the case of renal insufficiency).
• Lumasiran: Subcutaneous injection with dose and timing adjusted according to body weight and duration
of treatment:
oo Initial Dose: Bodyweight < 10 kg: 6 mg/kg; Bodyweight 10-20 kg: 6 mg/kg; Bodyweight > 20 kg:
3 mg/kg; once per month for 3 months subcutaneous injection.
oo Maintenance starting one month after initial doses: Bodyweight < 10 kg: 3 mg/kg 1-mal monthly;
Bodyweight 10-20 kg: 6 mg/kg every 3 months, Bodyweight > 20 kg: 3 mg/kg.
4.6.3.1 Summary of evidence and recommendation for the management of primary hyperoxaluria
Pyridoxine can reduce the urinary oxalate excretion in primary hyperoxaluria type 1. 3
Lumasiran can reduce the urinary oxalate excretion in primary hyperoxaluria type 1. 1

Prescribe pyridoxine for primary hyperoxaluria type 1. Strong
4.6.4 Enteric hyperoxaluria [615, 620, 677-679]

Enteric hyperoxaluria is a particularly problematic condition in patients with intestinal malabsorption of fat.
This abnormality is associated with a high risk of stone formation and is seen after intestinal resection and
malabsorptive bariatric surgery, as well as in Crohn’s disease and pancreas insufficiency. In addition to
hyperoxaluria, these patients usually present with hypocitraturia due to loss of alkali. Urine pH is usually low,
as are urinary calcium and urine volume. All these abnormalities contribute to high levels of supersaturation
with calcium oxalate, crystalluria, stone formation, and less frequently to nephrocalcinosis and CKD. Specific
preventive measures are:
• restricted intake of oxalate-rich foods [615];
• restricted fat intake [615];
• calcium supplementation at meal times to enable calcium oxalate complex formation in the intestine [620,
677-679];
• sufficient fluid intake to balance intestinal loss of water caused by diarrhoea;
• alkaline citrates to raise urinary pH and citrate.

Alkaline citrates can be beneficial to replace citrate loss and raise urine pH. 3
Calcium supplements with meals enable calcium oxalate complex formation in the intestine. 2
Reduction in dietary fat and oxalate can be beneficial in intestinal malabsorption. 3

Prescribe alkaline citrates for enteric hyperoxaluria. Weak
Advise patients to take calcium supplements with meals. Strong
Advise patients to follow a diet with a low fat and oxalate content. Weak
4.6.5 Renal tubular acidosis [597, 636, 680, 681]

Renal tubular acidosis is caused by severe impairment of proton or bicarbonate handling along the nephron.
Kidney stone formation most probably occurs in patients with distal RTA type I. Figure 4.5 outlines the
diagnosis of RTA. Table 4.7 shows acquired and inherited causes of RTA.
Figure 4.5: Diagnosis of renal tubular acidosis
Urinary pH
constantly > 5.8
Normal bicarbonate Low bicarbonate

in BGA in BGA
RTA Type I RTA Type I

possible complete
Ammonium chloride
loading test**
(NH4CI 0.1 g/kg body weight)
Urine pH < 5.4 Urine pH > 5.4

RTA excluded RTA - incomplete
BGA = blood gas analysis; RTA = renal tubular acidosis.

** An alternative ammonium chloride loading test using NH4Cl load with 0.05 g/kg body weight over three days
might provide similar results and may be better tolerated by the patient [682]. A second alternative in these
cases could be the furosemide/fludrocortisone acidification test [683].
Renal tubular acidosis can be acquired or inherited. Reasons for acquired RTA can be chronic obstructive
uropathy, recurrent pyelonephritis, acute tubular necrosis, renal transplantation, analgesic nephropathy,
sarcoidosis, Sjögren syndrome and other autoimmune diseases, medullary sponge kidney, liver cirrhosis,
sickle cell anaemia, idiopathic hypercalciuria, and primary parathyroidism; it may also be drug-induced (e.g.,
amphotericin B, foscarnet, lithium, zonisamide and other carbonic anhydrase inhibitors).

Table 4.7: Inherited causes of renal tubular acidosis
Type - inheritance Gene/gene product/function Phenotype
Autosomal dominant SLC4A1/AE1/Cl-bicarbonate Hypercalciuria, hypokalaemia,
exchanger rickets/osteomalacia
Autosomal recessive with hearing ATP6V1B1/B1 sub-unit of vacuolar Hypercalciuria, hypokalaemia,
loss H-ATPase/proton secretion rickets/osteomalacia
Autosomal recessive ATP6V0A4/A4 sub-unit of vacuolar Hypercalciuria, hypokalaemia,
H-ATPase/proton secretion rickets/osteomalacia
More rarely biallelic causative variants in FOXI1 and WDR72 genes have also been identified. The main
therapeutic aim of RTA treatment is restoring a normal acid-base equilibrium. Despite the alkaline pH of urine
in RTA, alkalinisation using alkaline citrates or sodium bicarbonate is important for normalising the metabolic
changes (intracellular acidosis) responsible for stone formation (Table 4.8) and bone demineralisation. The alkali
load reduces tubular re-absorption of citrate, which in turn normalises citrate excretion. Therapeutic success
can be monitored by venous blood gas analysis (base excess: ± 2.0 mmol/L) in complete RTA. If excessive
calcium excretion (> 8 mmol/day) persists after re-establishing acid-base equilibrium, thiazides may lower
urinary calcium excretion.
Table 4.8: Pharmacological treatment of renal tubular acidosis

Biochemical risk factor Indication for pharmacological Medication
therapy
Hypercalciuria Calcium excretion > 8 mmol/day Hydrochlorothiazide*,
- in adults: 25 mg/day initially, up to
50 mg/day
- in children: 0.5-1 mg/kg/day
Alternatives in adults:
Chlorthalidone 25 mg/day
Indapamide 2.5 mg/day
Inadequate urine pH Citrate excretion Alkaline citrate, 9-12 g/day divided
male < 1.7 mmol/day, in three doses
female < 1.9 mmol/day OR
Sodium bicarbonate, 1.5 g, three
times daily
*P atients on hydrochlorothiazides should be advised to get their skin checked on a regular basis as they have
4.6.5.1 Summary of evidence and recommendations for the management of tubular acidosis
Alkaline citrates can be beneficial in distal renal tubular acidosis to correct the intracellular acidosis. 2b
Thiazide and alkaline citrates are beneficial for hypercalciuria. 1a

Prescribe alkaline citrates for distal renal tubular acidosis. Strong
Prescribe thiazide and alkaline citrates for hypercalciuria. Strong
4.6.6 Nephrocalcinosis [684]

Nephrocalcinosis (NC) refers to increased calcium crystal deposition within the renal cortex or medulla and
occurs alone or in combination with renal stones. There are various metabolic causes. The main causes are:
HPT, primary and enteric hyperoxalurias, genetic and acquired RTA, medullary sponge kidney, vitamin D
metabolic disorders, sarcoidosis, idiopathic hypercalciuria and hypocitraturia, and genetic disorders, including
Dent’s disease, Bartter’s syndrome. The many causes of NC mean there is no single standard therapy.
Therapeutic attention must focus on the underlying metabolic or genetic disease, on the frequent association
with CKD while minimising the biochemical risk factors.

4.6.6.1 Diagnosis
Diagnosis requires the following blood analysis: PTH (in the case of increased calcium levels), vitamin D
and metabolites, vitamin A, sodium, potassium, magnesium, chloride, and bicarbonate. Urinalysis should
investigate urine pH profile at different times of the day daily urine volume, specific weight of urine, and levels
of calcium, oxalate, phosphate, uric acid, magnesium, and citrate [585].
4.7 Uric acid and ammonium urate stones

All uric acid and ammonium urate stone formers are considered to be at high risk of recurrence [27]. Uric acid
nephrolithiasis is responsible for approximately 10% of renal stones [685] and associated with hyperuricosuria
or low urinary pH. Hyperuricosuria may be a result of dietary excess, endogenous overproduction (enzyme
defects), myeloproliferative disorders, chemotherapy drugs, gout or catabolism [582]. Low urinary pH may be
caused by decreased urinary ammonium excretion (insulin resistance or gout), increased endogenous acid
production (insulin resistance, metabolic syndrome, or exercise-induced lactic acidosis), increased acid intake
(high animal protein intake), or increased base loss (diarrhoea) [582].
Ammonium urate stones are extremely rare, comprising < 1% of all types of urinary stones. They are
associated with UTI, malabsorption (inflammatory bowel disease and ileostomy diversion or laxative abuse),
phosphate deficiency, hypokalemia and malnutrition. Suggestions on uric acid and ammonium urate
nephrolithiasis are based on level 3 and 4 evidence. Chronic kidney disease is frequently observed.
4.7.1 Diagnosis
Figure 4.6 shows the diagnostic algorithm for uric acid stones and figure 4.7 shows the therapeutic algorithm
for uric acid and ammonium urate stones. Blood analysis requires measurement of creatinine, potassium, and
uric acid levels. Urinalysis requires measurement of urine volume, urine pH profile, specific weight of urine, and
uric acid level. Urine culture is needed in the case of ammonium urate stones.
4.7.2 Interpretation of results

Uric acid and ammonium urate stones form under completely different biochemical conditions. Low urine pH
promotes uric acid crystallisation.
Hyperuricosuria is defined as uric acid excretion > 4 mmol/day and day and > 5 mmol/day in adult females and
males, respectively or > 0.12 mmol/kg/day in children. Hyperuricaemia may be present, but there is only weak
evidence for its association with stone formation [686].
Hyperuricosuric calcium oxalate stone formation can be distinguished from uric acid stone formation by
urinary pH, which is usually > 5.5 in calcium oxalate stone formation and < 5.5 in uric acid stone formation
and occasional absence of hyperuricosuria in patients with pure uric acid stones [687, 688]. Ammonium urate
crystals form in urine at pH > 6.5, high uric acid concentration when ammonium is present [689, 690].

General preventive measures are recommended for fluid intake and diet. Hyperuricosuric stone formers benefit
from purine reduction in their daily diet. Figure 4.6 describes pharmacological treatment [27, 685, 687-697]. For
uric acid stones, allopurinol may change the stone composition distribution in patients with gout to a pattern
similar to that in stone formers without gout [698].

Uric Acid Nephrolithiasis
Hyperuricosuria Low urinary pH Low urine volume
superactivity; XO = xanthine oxidase.

Decreased
Increased
Urate over- URAT 1 Enzymatic urinary Increased acid Increased Chronic Dehydration
Uricosuric drugs endogenous acid
production mutations deficiencies ammonium intake base loss
production Excessive Respiration /
excretion
Exercise
Chronic Diarrhoea
Figure 4.6: Diagnostic algorithm for uric acid stones
1) Gout
1) HGPT
2) High dietary purine
1) Probenecid deficiency 1) Insulin
intake
2) High-dose 2) PRPS 1) Insulin resistance
3) Myeloproliferative
salicylates Hypouricemic overactivity resistance 2) Metabolic High animal-
disorders Diarrhoea
3) Radiocontrast hyperuricosuria 3) G6P 2) Gout syndrome protein intake
4) Haemolytic
agents deficiency 3) ADPKD Exercise-induced
anaemia
4) Losartan 4) XO lactic Acidosis
5) Chemotherapy-
deficiency
induced tumour lysis
ADPKD = autosomal dominant polycystic kidney disease; G6P = glucose-6 phosphate dehydrogenase;
HGPT = hypoxanthine guanine phosphorybosyl transferase; PRPS = phosphoribosyl-pyrophosphate synthetase
55
Figure 4.7: Therapeutic algorithm for uric acid- and ammonium urate stones
Uric acid- and urate-

containing stones
Ammonium
Urate acid stone
urate stones
Basic evaluation Basic evaluation
Hyperacidic Urine
Hyperuricosuria
urine pH < 5.5 pH > 6.5
Alkaline citrate > 4.0 mmol/d UTI

9-12 g/d1 > 4.0 mmol/d L-methionine
or and 200-500 mg tid
Sodium Hyperuricaemia Target urine-pH
bicarbonate > 380 μmol 5.8-6.2
1.5 g tid2 Allopurinol
Antibiotics
100 mg/d
Dose depends
on targeted Allopurinol
Correction
urine pH 100-300 mg/d
of factors
predisposing
amm.urate
stone
Prevention Chemolitholysis formation4
urine pH 6.2-6.8 urine pH 6.5-7.23
1 d: day.
2 tid: three times a day.
3 A higher pH may lead to calcium phosphate stone formation.
4 In patients with high uric acid excretion, allopurinol may be helpful.
4.7.4 Summary of evidence and recommendations for the management of uric acid- and
ammonium urate stones
Alkaline citrates can be beneficial to alkalinise the urine in uric acid stone formers. 3
Allopurinol can be beneficial in hyperuricosuric urate stone formers. 1b

Prescribe alkaline citrates to alkalinise the urine in uric acid stone formers. Strong
Prescribe allopurinol in hyperuricosuric urate stone formers. Strong

4.8 Struvite and infection stones
All infection-stone formers are deemed at high risk of recurrence. Struvite stones represent 2-15% of the
stones sent for analysis. Stones that contain struvite may originate de novo or grow on pre-existing stones,
which are infected with urea-splitting bacteria [699]. There are several factors predisposing patients to struvite
stone formation (Table 4.9) [700]. A number of studies have reported that urinary metabolic alterations can be
disclosed in 36-81% of patients with mixed struvite stones [701-706].
4.8.1 Diagnosis
Blood analysis requires measurement of creatinine, and urinalysis requires repeat urine pH measurements and
urine culture. In cases of mixed struvite stones the search of metabolic abnormalities in 24 hour urine after
stone removal and infection control is suggested.
4.8.2 Interpretation
Infection stones contain the following minerals: struvite and/or carbonate apatite and/or ammonium urate.
Urine culture typically provides evidence for urease-producing bacteria, which increase ammonia ions and
develop alkaline urine (Table 4.10). Carbonate apatite starts to crystallise at a urine pH level of 6.8. Struvite only
precipitates at pH > 7.2 [707, 708]. A mixed struvite stones, i.e. containing a high percentage of calcium oxalate
and carbonate apatite, suggests the over infection of a “metabolic” calcium oxalate or calcium phosphate
stone [706]. Proteus mirabilis accounts for more than half of all urease-positive UTIs [709, 710].

General preventive measures are recommended for fluid intake and diet. Specific measures include complete
surgical stone removal [700], short- or long-term antibiotic treatment [711], urinary acidification using
methionine [642] or ammonium chloride [712], and advice to restrict intake of urease [713, 714]. For persistent
infections/colonisation, acetohydroxamic acid may be an option [713, 714] (Figure 4.8); however, it is not
licensed/available in all European countries.
Eradication of infection after complete stone removal is desirable. The evidence regarding the
duration of post-operative antibiotic administration is inconclusive.
Removing the stone material as completely as possible with surgery can reduce ongoing infection. 3
Antibiotics are beneficial after complete stone removal. 3
Ammonium chloride, 1 g, two or three times daily, can ensure urinary acidification to prevent recurrent 3
infection.
Methionine, 200-500 mg, one to three times daily, can be used as an alternative to ammonium 3
chloride, to ensure urinary acidification.
Treatment of underlying metabolic abnormalities reduces recurrence of mixed struvite stones. 3
Urease inhibitors in case of severe infection are occasionally used (if licensed). 1b

Surgically remove the stone material as completely as possible. Strong
Prescribe antibiotics in case of persistent bacteriuria. Strong
Prescribe ammonium chloride, 1 g, two or three times daily to ensure urinary acidification. Weak
Prescribe methionine, 200-500 mg, one to three times daily, as an alternative, to ensure Weak
urinary acidification.
Table 4.9: Factors predisposing to struvite stone formation

• Neurogenic bladder • Urethral stricture
• Spinal cord injury/paralysis • Benign prostatic hyperplasia
• Continent urinary diversion • Bladder diverticulum
• Ileal conduit • Cystocele
• Foreign body • Calyceal diverticulum
• Stone disease • UPJ obstruction
• Indwelling urinary catheter

Table 4.10: Most important species of urease-producing bacteria
Obligate urease-producing bacteria (> 98%)
• Proteus spp.
• Providencia rettgeri
• Morganella morganii
• Corynebacterium urealyticum
• Ureaplasma urealyticum
Facultative urease-producing bacteria
• Enterobacter gergoviae
• Klebsiella spp.
• Providencia stuartii
• Serratia marcescens
• Staphylococcus spp.
CAUTION: 0 -5% of Escherichia coli, Enterococcus spp. and Pseudomonas aeruginosa strains may
produce urease.
Figure 4.8: Diagnostic and therapeutic algorithm for infection stones.
Infection stones
(Struvite carbon apatite
Ammonium urate1)
Basic evaluation
Urease Urinary pH
producing Treatment (Carbon apatite > 6.8
bacteria Struvite > 7.2)
Complete
surgical Urine Urease
removal Antibiotics
acidification inhibition*
is mandatory
Percutaneous
Ammonium Methionine
chemolysis may Short or AHA2
chloride 200-500 mg
be a useful long course 15 mg/kg/day
1 g bid or tid 1-3 times/d
adjunct
1 Discussed with uric acid stones.

2 Acetohydroxamic acid.
* When nationally available.
bid = twice a day; tid = three times a day; AHA = acetohydroxamic acid.

4.9 Cystine stones
Cystine stones account for 1-2% of all urinary stones in adults and 6-8% of the stones reported in paediatric
studies [37, 715]. All cystine stone formers are deemed at high risk of recurrence and CKD [716, 717].
4.9.1 Diagnosis
Blood analysis includes measurement of creatinine, and urinalysis includes measurement of urine volume, pH
profile, specific weight, and cystine. Since the disease may be asymptomatic, siblings of cystinuric patients
should be investigated for cystinuria [718].
Interpretation
• Cystine is poorly soluble in urine and crystallises spontaneously within the physiological urinary pH range.
• Cystine solubility depends strongly on urine pH: at pH 6.0, the limit of solubility is 1.33 mmol/L.
• Routine analysis of cystine is not suitable for therapeutic monitoring.
• Regardless of phenotype or genotype of the cystinuric patient, the clinical manifestations are the same
[719].
• There is no role for genotyping patients in the routine management of cystinuria [720, 721].
• Reductive therapy targets the disulphide binding in the cystine molecule. For therapy monitoring, it is
important to differentiate between cystine, cysteine and drug-cysteine complexes. However, available
methods to monitor cystinuria treatment are cumbersome [722, 723], or inaccurate including high-
performance liquid chromatography (HPLC) which may be able to differentiate between the different
complexes formed by therapy [69].
• Quantitative 24-hour urinary cystine excretion confirms the diagnosis in the absence of stone analysis.
• Levels above 0.125 mmol/day (30 mg/day) are considered abnormal [724, 725].

General preventative measures for fluid intake and diet are recommended. A diet low in methionine may
theoretically reduce urinary excretion of cystine; however, patients are unlikely to comply sufficiently with such
a diet. A restricted intake of sodium is more easily achieved and is more effective in reducing urinary cystine.
Patients are usually advised to avoid sodium consumption > 2 g/day (5 g NaCl) [726]. A high level of diuresis
is of fundamental importance, aiming for a 24-hour urine volume of > 3 L [719, 726-728]. A considerable fluid
intake evenly distributed throughout the day is necessary.
4.9.2.1 Pharmacological treatment of cystine stones

The main therapeutic option for avoiding cystine crystallisation is to maintain urine pH > 7.5, to improve
cysteine solubility and ensure appropriate hydration with a minimum of 3.5 L/day in adults, or 1.5 L/m2
body surface area in children [719, 726-728]. Home monitoring of the urine pH is suggested because of the
possibility to self-adjust alkaline treatment keeping the urine pH in range [69].
Free cystine concentration can be decreased by reductive substances, which act by splitting the
disulphide binding of cystine.
Tiopronin is currently the best choice for cystine reduction. However, side effects often lead to
treatment termination, for example when nephrotic syndrome develops or when there is poor compliance,
especially with long-term use. After carefully considering the risk of early tachyphylaxis, put into place a dose-
escape phenomenon for long-term use, and recurrence risk. Tiopronin is recommended at cystine levels > 3.0
mmol/day (720 mg/day) or in the case of recurring stone formation, notwithstanding other preventive measures
[719, 726-728]. Spot measurement of urine protein should be performed at baseline and during follow-up.

Figure 4.9: Metabolic management of cystine stones [729]
Cystine Stones
Basic evaluation
Appropriate hydration with

> 3.5 L/d in adults and
1.5 L/m2 body surface in
children
and
adjust urine pH
between 7.5 and 8.0
with
alkaline citrates or
sodium bicarbonate
Cystine excretion Cystine excretion

< 3 mmol/d > 3 mmol/d
Possible add. treatment Additional treatment with

with tiopronin tiopronin 250 mg/d up to
(depending on recurrence) 2,000 mg/d max. dos.
4.9.3 Summary of evidence and recommendations for the management of cystine stones
Increasing fluid intake so that 24-hour urine volume exceeds 3 L is used to dilute the cystine. 3
Alkaline citrates 3-10 mmol two or three times daily can be used to achieve pH > 7.5. 3
Tiopronin, 250-2,000 mg/day can be used to reduce stone formation in patients with cystine excretion, 3
> 3 mmol/day, or when other measures are insufficient.

Therapeutic measures
Urine dilution Strong
Advise patients to increase their fluid intake so that 24-hour urine volume exceeds 3 L.
Alkalinisation Strong
Prescribe potassium citrate 3-10 mmol two or three times daily, to achieve pH > 7.5 for
patients with cystine excretion < 3 mmol/day.
Complex formation with cystine Strong
For patients with cystine excretion, > 3 mmol/day, or when other measures are insufficient:
prescribe in addition to other measures tiopronin, 250-2,000 mg/day.

4.10 2,8-Dihydroxyandenine stones and xanthine stones
All 2,8-Dihydroxyadenine and xanthine stone formers are considered to be at high risk of recurrence. Both
stone types are rare. Diagnosis and specific prevention are similar to those for uric acid stones [27].
4.10.1 2,8-Dihydroxyadenine stones

A genetically determined defect of adenine phosphoribosyl transferase causes high urinary excretion of poorly
soluble 2,8-Dihydroxyadenine [730]. High-dose allopurinol or febuxostat are important options but should be
given with regular monitoring [731].
4.10.2 Xanthine stones

Patients who form xanthine stones usually show decreased levels of serum uric acid. There is no available
pharmacological intervention.
4.10.3 Fluid intake and diet

Recommendations for general preventive measures apply. Pharmacological intervention is difficult; therefore,
high fluid intake ensures optimal specific weight levels of urine < 1.010 (urine specific gravity). A purine-
reduced diet decreases the risk of spontaneous crystallisation in urine.
4.11 Drug-induced stones

Drug stones are induced by pharmacological treatment [627, 732] (Table 4.10). Two types exist:
• stones formed by crystallised compounds of the drug;
• stones formed due to unfavourable changes in urine composition under drug therapy.
Table 4.11: Compounds that cause drug stones

Active compounds crystallising in urine Substances impairing urine composition
• Allopurinol/oxypurinol • Acetazolamide
• Amoxicillin/ampicillin • Allopurinol
• Ceftriaxone • Aluminium magnesium hydroxide
• Quinolones • Ascorbic acid
• Ephedrine • Calcium
• Indinavir and other HIV-protease inhibitors • Furosemide
• Magnesium trisilicate • Laxatives
• Sulphonamides • Losartan
• Triamterene • Methoxyflurane
• Orlistat
• Vitamin D
• Topiramate
• Zonisamide
4.12 Matrix Stones

Pure matrix stones are extremely rare with less than 70 cases described in the literature. They are more
prevalent in females. The main risk factors are recurrent UTIs, especially due to P. mirabilis or E. coli, previous
surgery for stone disease, chronic renal failure, and haemodialysis. Complete endourological removal,
frequently via the percutaneous approach, is critical. Given the rarity of matrix calculi a specific prophylactic
regimen to minimise recurrence cannot be recommended. Eliminating infections and prophylactic use of
antibiotics are most commonly proposed [733].
4.13 Unknown stone composition [20]

An accurate medical history is the first step towards identifying risk factors as summarised in sections 3.1.3
and 4.13.1 and Fig. 4.1.
Diagnostic imaging begins with US examination of both kidneys to establish whether the patient is stone free.
Stone detection by US should be followed by KUB and unenhanced multislice CT in adults to differentiate
between calcium-containing and non-calcium stones.
Blood analysis demonstrates severe metabolic and organic disorders, such as renal insufficiency,
HPT or other hypercalcaemic states and hyperuricaemia. In children, hyper with low GFR oxalaemia should
additionally be screened for.
Urinalysis is performed routinely with a dipstick test as described above. Urine culture is required if
there are signs of infection. Urine pH < 5.5 in 24-hr urine collection indicates hyper acidic urine, which could

promote uric acid crystallisation. Urine pH > 6.2 in 24-hr urine collection may indicate RTA, if UTI is excluded
[679, 681].
Microscopy of urinary sediment can help to discover rare stone types because crystals of
2,8-Dihydroxyadenine, cystine and xanthine are pathognomonic for the corresponding disease. In cases in
which the presence of cystine is doubtful, a cyanide nitroprusside colorimetric qualitative test can be used to
detect the presence of cystine in urine, with a sensitivity of 72% and specificity of 95%. False-positive results
are possible in patients with Fanconi’s syndrome or homocystinuria, or in those taking various drugs, including
ampicillin or sulfa-containing medication [734, 735].
Following this programme, the most probable stone type can be assumed, and specific patient
evaluation can follow. Further metabolic investigations will depend on the presence of risk factors (see section
3.1.3) and on the results of previous investigations. However, if any expulsed stone material is available, it
should be analysed by diagnostic confirmation or correction.
4.13.1 Recommendations for investigations for the assessment of patients with stones of unknown
composition [21, 27, 68, 627]

Investigation Rationale for investigation
Take a medical history • Stone history (former stone events, family history) Strong
• Dietary habits
• Medication chart
Perform diagnostic imaging • Ultrasound in the case of a suspected stone Strong
• Un-enhanced helical computed tomography
• Determination of Hounsfield units provides
• Information about the possible stone composition
Perform a blood analysis • Creatinine Strong
• Calcium (ionised calcium or total calcium + albumin)
• Uric acid
Perform a urinalysis •U rine pH profile (measurement after each voiding, Strong
minimum four times daily)
•D ipstick test: leukocytes, erythrocytes, nitrites,
protein, urine pH, specific weight
• Urine cultures
• Microscopy of urinary sediment (morning urine)
• Cyanide nitroprusside test (cystine exclusion)
Further examinations depend on the results of the

investigations listed above.
5. FOLLOW-UP OF URINARY STONES

Patients suffering from urinary tract lithiasis have a predisposition to develop symptoms, complications, and
recurrence of stones. Despite the rich literature published on urinary lithiasis very little has been written about
how lithiasis patients should be monitored after their treatment.
There is no general agreement on whether and when stone patients should be released from their follow-up,
nor when and how follow-up should occur for patients who need it. The main reason for this lack of agreement
is the great clinical heterogeneity of stone disease among patients.
The EAU Urolithiasis Guidelines Panel performed a systematic review questioning the benefits and harms of
scheduled follow-up for patients who underwent definitive treatment (extracorporeal shock wave lithotripsy,
ureteroscopy, percutaneous nephrolithotripsy, medical chemoprophylaxis) for upper urinary tract stone disease
[736].
The Panel aimed to answer three main questions regarding urolithiasis follow-up: a) In patients with no residual
fragments, does imaging follow-up after treatment for upper urinary tract stones offer more clinical benefits

than harms compared with no scheduled follow-up? b) In patients with residual fragments, does imaging
follow-up after treatment for upper urinary tract stones offer more clinical benefits than harms compared with
no scheduled follow-up? and c) Does biochemical urine analysis follow-up after treatment for upper urinary
tract stones offer more clinical benefits than harms compared with no scheduled follow-up? There was a lack
of comparative studies regarding follow-up versus no follow-up, so the primary endpoints were not reached.
The panel used the data from the eligible observational and randomised studies included in the systematic
review to identify the time of patient discharge after follow-up according to stone disease status (stone-free
patients, patients with residual stones, patients with metabolic abnormalities), and to come to a consensus on
frequency of follow-up and use of investigations.
From a pooled analysis of 5,467 stone-free patients, the Panel estimated that for a safety margin of 80%,
patients should be followed-up using imaging, for at least two years (radiopaque stones), or at least three years
(radiolucent stones) before discharge, while for a safety margin of 90% patients should be discharged after
five years of no recurrence. Regarding residual disease, patients with fragments < 4mm could be offered either
surveillance for up to four years, since intervention rates range between 17-29%, disease progression between
9-34% and spontaneous passage between 21-34% at 49 months. Patients with larger residual fragments
should be offered further definitive intervention, since intervention rates are high (24-100%). Insufficient data
exist for high-risk patients, but current literature dictates that patients who are adherent to targeted medical
treatment seem to experience less stone growth or re-growth of residual fragments and may be discharged
after 36-48 months of non-progressive disease on imaging (Figure 5.1).
A Panel consensus was reached after extensive discussion of data regarding frequency of follow-up. In
stone-free general population, the vast majority of patients remained stone-free during the 1st year, in contrast
with patients with metabolic abnormalities not under targeted medical treatment, < 40% were stone-free
after three years of follow-up. Therefore, a more extensive follow-up is proposed for patients with metabolic
abnormalities. Patients with small residual fragments < 4mm, showed a spontaneous expulsion at 17.9-46.5%
and growth rate at 10.1-40.7% during the 1st year, while patients with larger fragments (> 4 mm) had only
9% of spontaneous expulsion at three years. Therefore, patients with small < 4mm, asymptomatic fragments
should be followed-up or scheduled for an intervention according to patient preference, while those with larger
stones should primarily be offered re-intervention. Proposed imaging consists of plain X-ray KUB and/or US,
based on stone characteristics and clinicians’ preferences. Computed tomography scan should be reserved for
symptomatic disease or pre-operative imaging, in order to avoid extensive radiation exposure (Figure 5.2) [736].
The information on stone composition can be used to counsel patients to set expectations and help plan the
need for follow up and medical stone management [737].

64
Follow-up of stone-disease
patients after treatment
Patients with residual

Stone Free Patients High-risk patients***
fragments
Not on medical
On medical treatment treatment
80% "safety margin" 80% "safety margin" ≤ 4 mm or dust
90% "safety margin" > 4 mm Follow-up for 4 years Follow-up for at least 4
*** Patients with diagnosed metabolic abnormalities.

2 years X-ray follow- 3 years X-ray +/- US Follow-up for 4
Follow-up for 5 Schedule and consider discharge years. Strongly consider
up for radiopaque follow-up for years or
years* re-intervention for non-progressive follow-up until 10 years
stones radiolucent stones intervention**
** According to patient preference or symptomatic disease.

disease due to high-risk of
recurrence****
**** Lifelong follow-up is advised but data are available up to 10 years.

Figure 5.1: Follow-up duration of Urinary stone patients after treatment
* Not enough data about subgroup analysis of radiolucent and radiopaque stones.

Figure 5.2: Consensus on follow-up frequency and imaging modality to use after treatment
monitoringa
imaging vs.
Counsel on
Treatment
Metabolic
discharge
Months
Imaging
Imaging
Imaging
60
monitoringa
imaging vs.
Counsel on
Treatment
Metabolic
discharge
Months
Imaging
Imaging
Imaging
48
monitoringa
imaging vs.
Counsel on
Treatment
Metabolic
discharge
Months
Imaging
Imaging
Imaging
36
monitoringa
Treatment
Metabolic
Months
Imaging
Imaging
Imaging
24
+
X
Months
Imaging
18
X
monitoringa
Treatment
Metabolic
Months
Imaging
Imaging
Imaging
Imaging
12
monitoringa
Treatment
Metabolic
Months
Imaging
Imaging
Imaging
Imaging
+
+
6
High-risk
Low-risk
population
Fragments
Fragments
High-risk
General
> 4mm+
≤ 4mm*
fragments
Stone-free
Residual
Follow-up
treatment
after
Stone free = No stone fragments on post-operative imaging (i.e. no stone fragments on CT/KUB/US).
High-Risk = Known biochemical abnormality (i.e,: hypercalciuria, hypocitraturia, hyperuricosuria, RTA or high-risk
stone type such as struvite). Imaging = plain film KUB &/or kidney ultrasonography (KUS) based on clinicians’
preference and stone characteristics. Consider CT if patient is symptomatic or if intervention is planned.
* Clinicians may choose the imaging-only pathway in patients with fragments < 2 mm.
o Treatment monitoring for side effects, intolerance, and compliance.
+ Panel recommends reintervention however close follow up may be considered for some patients at high risk
for reintervention based on clinicians’ preference.

6. BLADDER STONES
6.1 Prevalence, aetiology, and risk factors of bladder stones
Bladder stones constitute only approximately 5% of all urinary tract stones [738] yet are responsible for 8% of
urolithiasis-related mortalities in developed nations [739]. The incidence is higher in developing countries [740].
The prevalence of bladder stones is higher in males, with a reported male: female ratio between 10:1 and 4:1
[741, 742]. The age distribution is bimodal: incidence peaks at three years in children in developing countries
[741, 743], and 60 years in adulthood [742].
The aetiology of bladder stones is typically multi-factorial [742]. Bladder stones can be classified as primary,
secondary, or migratory [744].
Primary or endemic bladder stones occur in the absence of other urinary tract pathology, typically seen in
children in areas with poor hydration, recurrent diarrhoea, and a diet deficient in animal protein [745].
Secondary bladder stones occur in the presence of other urinary tract abnormalities, which include bladder
outlet obstruction (BOO), neurogenic bladder dysfunction, chronic bacteriuria, foreign bodies (including
catheters), bladder diverticula and bladder augmentation or urinary diversion. In adults, BOO is the most
common predisposing factor for bladder stone formation and accounts for 45-79% of vesical calculi [742, 746-
749].
Migratory bladder stones are those which have passed from the upper urinary tract where they formed and
may then serve as a nidus for bladder stone growth. Patients with bladder calculi are more likely to have a
history of upper tract stones and risk factors for their formation [750].
A wide range of metabolic urinary abnormalities can pre-dispose to calculi anywhere in the urinary tract, which
is covered in more detailed in Section 4. Metabolic Evaluation and Recurrence Prevention. There is a paucity of
studies on the specific metabolic abnormalities which predispose to bladder stones.
Bladder stones will form in 3-4.7% of men undergoing surgery for benign prostatic obstruction (BPO) [751,
752], 19-39% and 36-67% of motor-incomplete and motor-complete spinal cord injury patients, respectively
[753], and 2.2% of patients with long-term catheters [754]. In men with chronic urinary retention secondary to
BPO, the 24-hr urine of 27 men with bladder stones had a higher uric acid supersaturation (2.2 vs. 0.6 mmol/L,
p < 0.01), lower magnesium (106 vs. 167 mmol/L, p = 0.01) and lower pH (5.9 vs. 6.4, p = 0.02) than the 21
men without bladder stones [750]. It is therefore likely that patients with these conditions who form bladder
stones also have an abnormal urine composition which pre-disposes them to bladder stone formation.
The metabolic abnormalities which pre-dispose patients to form secondary bladder stones are poorly
understood. Stone analysis of 86 men with a BPO-related bladder stone demonstrated 42% had calcium-
based stones (oxalate, phosphate), 33% had magnesium ammonium phosphate, 10% had mixed stones and
14% had urate stones [742]. Similar findings were reported in more recent studies [755-757] and it is therefore
likely that multiple metabolic factors pre-dispose patients to secondary bladder stone formation.
The exact metabolic basis for primary bladder stones is poorly understood and likely multi-factorial. Low urine
volume (poor hydration) is the most consistently demonstrable abnormality [758-760]. Twenty-four-hour urine
analysis in children with endemic bladder stones is reported in two studies. Of 57 children in Pakistan, 89.5%
had hypocitraturia, 49% had a low urine volume, 44% had hyperoxaluria and 42% had hypocalciuria [758].
Of 61 children in India, stone formers had higher urine calcium and uromucoid concentrations than controls
[759]. One study from Thailand compared 24-hour urine analyses from children from a rural area with a high
prevalence of bladder stones with those from an urban area: rural children had lower urine volumes and,
despite equal calcium, oxalate, and uric acid concentrations, crystalluria with uric acid and calcium oxalate
crystals was more prevalent in rural children [760].

Table 6.1 Bladder stones classified by aetiology
Type of bladder stone Primary Secondary Migratory
Cause/Associations Occur in the absence BOO (e.g., BPO, urethral Form in the upper urinary
of other urinary tract stricture) tract, then passed into
pathology, typically in Neurogenic bladder the bladder where they
children in areas with dysfunction may be a nidus for stone
poor hydration, recurrent Chronic bacteriuria growth
diarrhoea, and a diet Foreign bodies (including
deficient in animal protein catheters)
Bladder diverticula
Bladder augmentation
Urinary diversion
BOO = Bladder Outlet Obstruction; BPO = Benign Prostatic Obstruction.
6.2 Presentation
The symptoms most commonly associated with bladder stones are urinary frequency, haematuria (which is
typically terminal) and dysuria or suprapubic pain, which are worst towards the end of micturition. Sudden
movement and exercise may exacerbate these symptoms. Detrusor over-activity is found in over two thirds of
adult male patients with vesical calculi and is significantly more common in patients with larger stones (> 4 cm).
However, recurrent urinary tract infections (UTIs) may be the only symptom [747, 748].
In children, symptoms may also include pulling of the penis, difficulties in micturition, urinary retention, enuresis
and rectal prolapse (resulting from straining due to bladder spasms). Bladder stones may also be an incidental
finding in 10% of cases [745, 761].
6.3 Diagnostic evaluation

6.3.1 Diagnostic investigations for bladder stones
Plain X-ray of KUB has a reported sensitivity of 21%-78% for cystoscopically detected bladder stones in adults
[747, 762]. Larger (> 2.0 cm) stones are more likely to be radiopaque [762]. However, plain X-ray provides
information on radio-opacity which may guide treatment and follow-up (see Section 3.2.3 X-ray characteristics,
for further information).
Ultrasound has a reported sensitivity and specificity of 20-83% and 98-100%, respectively for the detection
of bladder stones in adults [763, 764]. Computed tomography and cystoscopy have a higher sensitivity for
detecting bladder stones than US or X-Ray in adults [763, 764]. No study compares cystoscopy and CT for the
diagnosis of bladder stones. Cystoscopy has the advantage of detecting other potential causes for a patient’s
symptoms (e.g., bladder cancer), whilst CT can also assess upper tract urolithiasis (see also section 3.2.3 X-ray
characteristics) [765] .
There is a paucity of evidence for the investigation of bladder stones, particularly in children [86, 766]. See also
Section 3.3 Diagnostic evaluation, for further information on diagnostic imaging for urolithiasis. The principle of
ALARA should be applied, especially in children [767].
6.3.2 Diagnosing the cause of bladder stones

The cause of the bladder stone should be considered prior to bladder stone treatment as eliminating the
underlying cause will reduce recurrence rates [768]. The following should be performed where possible prior to
(or at the time of) bladder stone treatment:
• physical examination of external genitalia, peripheral nervous system (including digital rectal examination,
peri-anal tone, and sensation in men);
• uroflowmetry and post-void residual urine assessment;
• urine dipstick to include pH ± culture;
• metabolic assessment (see also section 3.3.2.3) including: serum (creatinine, (ionised) calcium, uric acid,
sodium, potassium, blood cell count);
• urine pH;
• stone analysis: in first-time formers using a valid procedure (X-ray diffraction or infrared spectroscopy).
The following investigations should also be considered for selected patients:

• upper tract imaging (in patients with a history of urolithiasis or loin pain);
• cysto-urethroscopy or urethrogram.

6.4 Disease Management
6.4.1 Conservative treatment and Indications for active stone removal
Migratory bladder stones in adults may typically be left untreated, especially asymptomatic small stones. Rates
of spontaneous stone passage are unknown, but data on ureteric stones suggest stones < 1 cm are likely
to pass in the absence of BOO, bladder dysfunction or long-term catheterisation (see section 3.4.9 Specific
stone management of ureteral stones).
Primary and secondary bladder stones are usually symptomatic and are unlikely to pass
spontaneously: active treatment of such stones is usually indicated.
6.4.2 Medical management of bladder stones

There is a paucity of evidence on chemolitholysis of bladder stones. However, guidance on the medical
management of urinary tract stones in section 3.4.9 Specific stone management of ureteral stones, can be
applied to urinary stones in all locations. Uric acid stones can be dissolved by oral urinary alkalinisation when a
PH > 6.5 is consistently achieved, typically using an alkaline citrate or sodium bicarbonate. Regular monitoring
is required during therapy (see section 3.4.4 Chemolysis). Irrigation chemolysis is also possible using a
catheter; however, this is time consuming and may cause chemical cystitis and is therefore not commonly
employed [148, 769].
6.4.3 Bladder stone interventions

Minimally invasive techniques for the removal of bladder stones have been widely adopted to reduce the risk
of complications and shorten hospital stay and convalescence. Bladder stones can be treated with open,
laparoscopic, robotic assisted laparoscopic, endoscopic (transurethral or percutaneous) surgery or ESWL [770].
6.4.3.1 Suprapubic cystolithotomy

Open suprapubic cystolithotomy is very effective but is associated with a need for catheterisation and longer
hospital stay in both adults and children compared to all other stone removal modalities [393]. In children, a
non-randomised study found that, if the bladder was closed meticulously in two layers, “tubeless” (drain-less
and catheter-less) cystolithotomy was associated with a significantly shorter length of hospital stay compared
with traditional cystolithotomy, without significant differences regarding late or intra-operative complications
provided that children with prior UTI, recurrent stones, or with previous surgery for anorectal malformation
(or other relevant surgery) were excluded [771].
6.4.3.2 Transurethral cystolithotripsy

In both adults and children, transurethral cystolithotripsy provides high SFRs and appears to be safe, with a
very low-risk of unplanned procedures and major post-operative and late complications [770].
6.4.3.2.1 Transurethral cystolithotripsy in adults

In adults, meta-analysis of four RCTs including 409 patients demonstrated that transurethral cystolithotripsy
has a shorter hospital stay and convalescence with less pain, but equivalent SFR and complications compared
to percutaneous cystolithotripsy [770]. Transurethral cystolithotripsy with a nephroscope was quicker than
percutaneous cystolithotripsy in three RCTs, although transurethral cystolithotripsy with a cystoscope was
slower than percutaneous cystolithotripsy [770].
Rates of urethral strictures following transurethral procedures were not robustly reported: studies report rates
between 2.9% and 19.6% during a follow up of 12 to 24 months [755, 770, 772].
One small RCT demonstrated a shorter duration of catheterisation, hospital stay and procedure with
transurethral cystolithotripsy than open cystolithotomy with similar SFR [770]. Meta-analysis of five RCTs found
significantly shorter procedure duration for transurethral cystolithotripsy using a nephroscope vs. cystoscope
with similar SFRs, hospital stay, convalescence, pain, and complications [773]. Two retrospective studies
(n=188) reported that using a resectoscope or nephroscope was associated with a shorter procedure duration
(p < 0.05) than a cystoscope for transurethral cystolithotripsy [774, 775]. This suggests that transurethral
cystolithotripsy is quicker when using a continuous flow instrument.
6.4.3.2.1.1 Lithotripsy modalities used during transurethral cystolithotripsy in adults

When considering lithotripsy modalities for transurethral cystolithotripsy, the Panel’s systematic review found
very low-quality evidence from five non-randomised studies (n=385) which found no difference in SFR between
modalities (mechanical, laser, pneumatic, ultrasonic, electrohydraulic lithotripsy [EHL] or washout alone) [770].
Unplanned procedures and major post-operative complications were low-rate events and were not significantly
different between lithotripsy modalities, although one non-randomised study (NRS) suggested these might be

higher with EHL or mechanical lithotripsy than pneumatic or ultrasonic lithotripsy [776]. All outcomes had very
low-quality of evidence (GRADE) [770]. High-powered lasers seem to reduce lithotripsy time. Laser lithotripsy
was faster than pneumatic lithotripsy (MD 16.6 minutes; CI: 23.51-9.69, p < 0.0001) in one NRS (n=62);
however, a laser was used with a resectoscope and the pneumatic device with a cystoscope [777]. The same
conclusion was stated in a meta-analysis of ten RCTs with high heterogeneity and small sample sizes in some
of the included RCTs [778]. Continuous vs. intermittent irrigating instrument may affect the operation time more
significantly than the choice of lithotripsy device [770].
6.4.3.2.1.2 Transurethral cystolithotripsy in children

In children, three NRS suggest that transurethral cystolithotripsy has a shorter hospital stay and catheterisation
time than open cystolithotomy, but similar stone-free and complication rates [779]. One small quasi RCT found
a shorter procedure time using laser vs. pneumatic lithotripsy for < 1.5 cm bladder stones with no difference
in SFR or other outcomes [780]. Another RCT (n=73) found shorter procedure time using pneumatic vs. laser
therapy for bladder stones < 1.5 cm with similar SFRs and higher (minor) complication rates for pneumatic
lithotripsy [781].
6.4.3.3 Percutaneous cystolithotripsy

6.4.3.3.1 Percutaneous cystolithotripsy in adults:
One NRS found a shorter duration of procedure and catheterisation and less blood loss for percutaneous,
compared with open surgery in adult male patients with urethral strictures; all patients in both groups were
rendered stone-free [757].
Meta-analysis of four RCTs comparing transurethral and percutaneous cystolithotripsy found a shorter hospital
stay for transurethral cystolithotripsy over percutaneous surgery. Transurethral cystolithotripsy was quicker
when using a nephroscope. There were no significant differences in SFRs, major post-operative complications
or re-treatment [770].
6.4.3.3.2 Percutaneous cystolithotripsy in children:

In children, three NRS suggest that percutaneous cystolithotripsy has a shorter hospital stay and
catheterisation time, but a longer procedure duration and more peri-operative complications than open
cystolithotripsy; SFRs were similar [4, 761, 770, 779].
A systematic review identified four non-randomised studies comparing percutaneous and transurethral
cystolithotripsy and found similar SFRs, but that transurethral surgery offers a shorter duration of
catheterisation and hospital stay [4, 761, 779]. In contrast, a transurethral approach may need a longer
operative time and shows a higher post-operative stricture rate [4]. One small NRS found a non-significant
increased risk of unplanned procedures (within 30 days of primary procedure) and major post-operative
complications for percutaneous operations compared with transurethral procedures; however, age and stone
size determined which intervention children underwent and all patients were rendered stone-free [761]. One
RCT compared 48 boys < 14 years undergoing transurethral lithotripsy vs. 49 boys undergoing percutaneous
lithotripsy with comparable success and complications rates; however, PCCL had a shorter operative time and
less need for stone disintegration [782].
6.4.3.4 Extracorporeal shock wave lithotripsy

Extracorporeal SWL is the least invasive therapeutic procedure [770].
6.4.3.4.1 Shock wave lithotripsy in adults

In adults, one RCT compared SWL with transurethral cystolithotripsy in 100 patients with < 2 cm bladder
stones presenting with acute urinary retention. Stone free rate after one SWL session favoured transurethral
cystolithotripsy (86% vs. 98%, p = 0.03); however, following up to three sessions of SWL, there was no
significant difference in SFR (94% vs. 98%, p = 0.3) [770, 783].
Two NRS compared transurethral cystolithotripsy vs. SWL and found no significant difference in SFR (97.0%
vs. 93.9%, p=0.99, 97.7% vs. 89.7% p=0.07) despite larger stones in transurethral cystolithotripsy patients
(4.2 vs. 2.5 cm, p=0.014; and 3.6 vs. 2.6 cm [p value not reported]) [784, 785].
Length of hospital stay appeared to favour SWL in all three studies (0 vs. 1 day, 4.8 vs. 0 days, p=0.02,
0.8 vs. 2.4 days, respectively) [783-785]. No significant differences in major post-operative or intra-operative
complications were reported in any study [783-785].

One NRS compared SWL vs. open cystolithotomy in just 43 patients. Stone sizes were not comparable
(2.5 vs. 7.4 cm, p < 0.001). Stone-free rates were not significantly different (93.9% vs. 100%, p=0.50).
Length of stay favoured SWL. There was no significant difference in intra-operative or major post-operative
complications [784].
6.4.3.4.2 Shock wave lithotripsy in children

One large NRS found lower SFR for SWL than both transurethral cystolithotripsy and open cystolithotomy,
despite treating smaller stones with SWL. However, the length of hospital stays favoured SWL over open
cystolithotomy, although this appeared to be comparable between SWL and transurethral cystolithotripsy [786].
6.4.3.5 Laparoscopic cystolithotomy

Laparoscopic cystolithotomy has been described in adults and is typically performed in combination with
simple prostatectomy using either traditional laparoscopy or with robotic assistance [787, 788]. A SR found no
studies comparing laparoscopic surgery with other procedures [770].
6.4.4 Treatment for bladder stones secondary to bladder outlet obstruction in adult men
Bladder stones in men aged over 40 years may be caused by BPO, the management of which should also
be considered. Bladder stones were traditionally an indication for a surgical intervention for BPO: a doctrine
which has been questioned by recent studies. One prospective study reports urodynamics (cystometrogram)
findings in 46 men aged > 60 years before and after bladder stone treatment [748]. Only 51% of men had BOO
while 10% had detrusor under-activity. Eighteen percent of men had a completely normal urodynamic study
and 68% had detrusor over-activity. There was no significant difference between pre- and post-bladder stone
removal urodynamic findings [748].
One NRS compared 64 men undergoing transurethral cystolithotripsy with either transurethral resection of
prostate (TURP) or medical management for BPO (α-blocker with or without 5-alpha reductase inhibitor). After
28 months follow-up, no men on medication had had a recurrence, but 34% underwent TURP: a high post-
void residual urine volume predicted the need for subsequent TURP [789]. Another observational study of
23 men undergoing cystolithotripsy and commencing medical management for BPO found 22% developed a
BPO related complication, including 17% who had recurrent stones [768]. One RCT comparing cystolithotripsy
with concomitant TURP to cystolithotripsy with medical management of bladder outlet obstruction with
Tamsulosin and finasteride, demonstrated that both groups had a significantly improved QMax, IPSS and PVR
at follow-up, although the TURP group had a longer procedure and catheterisation time [790]. Large prostates
and a high PVR (> 190 ml) were predictive of needing a TURP over time in the medical management cohort,
although this was based on only a small number of patients.
Large studies support the safety of performing BPO and bladder stone procedures during the same operation
with no difference in major complications compared to a BPO procedure alone [791-793]. An observational
study on 2,271 patients undergoing TURP found no difference in complications except UTIs, which occurred
slightly more frequently in patients with simultaneously treated bladder stones: 0% vs. 0.6%, p=0.044 [791]. An
observational study of 321 men undergoing Holmium laser enucleation of the prostate (HoLEP) found a higher
rate of early post-operative incontinence (26.8% vs. 12.5%, p=0.03) in men having concomitant transurethral
cystolithotripsy, but no difference in long-term continence rates [793]. Another larger multicenter observational
study of 963 patients undergoing HoLEP found no significant differences in frequency of complications in
patients with (n=54 (5.6%)) or without concomitant transurethral cystolithotripsy [794].
6.4.5 Special situations

6.4.5.1 Neurogenic bladder and stone formation
Patients with a neurogenic bladder secondary to spinal cord injury or myelomeningocele are at increased risk
of forming bladder stones. Within eight to ten years, 15-36% of patients with spinal cord injury will develop a
bladder stone [795-797]. According to a systematic review, the prevalence of stone formation depends on the
level of the spinal cord injury with 19-39% and 36-67% of respectively motor-incomplete and motor-complete
spinal cord injury patients developing bladder stones over time [753]. The absolute annual risk of stone
formation in spinal cord injury patients with an indwelling catheter is 4% compared with 0.2% for those voiding
with clean intermittent self-catheterisation (CISC) [798].
A study of 2,825 spinal cord injury patients over eight years found a 3.3% incidence of bladder stones: 2% with
CISC, 6.6% with indwelling urethral catheter, 11% with a suprapubic catheter and 1.1% in patients voiding
using reflex micturition [799]. However, another study of 457 spinal cord injury patients for six months found no
difference in bladder stones between urethral and suprapubic catheterisation [798]. Spinal cord injury patients

with an indwelling urethral catheter are six times more likely to develop bladder stones than patients with
normal micturition [797, 799].
The risk of stone recurrence after complete removal in spinal cord injury patients is 16% per year [798]. A RCT
of 78 spinal cord injury patients who perform CISC found a significant reduction in bladder stone formation
when twice weekly manual bladder irrigations were performed for six months (49% vs. 0%, p = < 0.0001),
as well as less symptomatic UTIs (41% vs. 8%; p = 0.001) [800]. However, this study excluded patients who
developed autonomic dysreflexia during bladder irrigations. The irrigation volume used was not reported.
6.4.5.2 Bladder Augmentation

The incidence of vesical calculus formation after bladder augmentation is 2-44% in adults [801-810], and
4-53% in children [810-824]. Following cystoplasty, stones form after 24-31 months in adults [802, 804, 809],
and after 25-68 months in children [815, 818, 819, 823, 825-827]. The reported cumulative incidence of bladder
stone formation after ten years is 28-36% and after twenty years is 41% [810, 828].
Risk factors for bladder stone formation after augmentation include excess mucus production, incomplete
bladder emptying, non-compliance with CIC or bladder irrigations, bacteriuria or urinary tract infections (due
to urease-producing bacteria), foreign bodies (including staples, mesh, non-absorbable sutures), drainage by
vesico-entero-cystostomy (Mitrofanoff or Monti) [472, 802, 805, 807, 808, 815, 819, 822, 828] and voiding by
CISC compared with those voiding spontaneously [806]. Gastric segment augmentation confers a lower risk of
bladder stones than ileal or colonic segment cystoplasty [811, 815, 819, 822].
In previous stone formers, the rate of recurrence is 15-44% in adults [802-804, 806, 809], and 19-56% in
children [472, 810, 811, 815, 817-820, 822, 827]. The risk of recurrence is greatest during the first two years, at
about 12% per patient per year, with the risk decreasing with time [827].
Daily, or three-times-weekly bladder irrigations reduce the incidence of bladder stones following bladder
augmentation or continent urinary diversion [472, 805]. A randomised study found that daily bladder irrigation
with 240 mL of saline reduced stone recurrences (p< 0.0002, p=0.0152) and symptomatic UTIs (p < 0.0001,
p < 0.0001) compared to 60mL or 120mL [805]. The frequency of bladder irrigations required is unclear.
6.4.5.3 Urinary diversion

The incidence of stone formation after urinary diversion with an ileal or colon conduit is 0-3% [829, 830]. The
incidence of stone formation is 0-34% in orthotopic ileal neobladders (Hautmann, hemi-Kock, Studer, T-pouch
or w-neobladder) [470, 806, 830-838], and 4-6% in orthotopic sigmoid neobladders (Reddy) [835, 839]. The risk
of pouch stone formation is 4-43% in adults with an ileocaecal continent cutaneous urinary diversion (Indiana,
modified Indiana, Kock or Mainz I) [464, 806, 829, 830, 838, 840]. The average interval from construction of
the urinary diversion to stone detection is 71-99 months [834, 841]. In children, the incidence of neobladder
stone formation is 30% after Mainz II diversion (rectosigmoid reservoir) [812], and 27% after Kock ileal reservoir
construction [824].
6.4.5.4 Treatment of stones in patients with bladder augmentation or urinary diversion

Stones may be removed by open or endoscopic surgery in patients with bladder augmentation or diversion
[817]. However, often access cannot be obtained through a continent vesico-entero-cystostomy without
damaging the continence apparatus; hence a percutaneous or open approach is typically preferred [817].
No studies comparing outcomes following procedures for stones in reconstructed or augmented bladders
were found. Two observational studies indicate that percutaneous lithotomy can be safely performed with
US or CT guidance in patients with reconstructed or augmented bladders [842, 843] and is proposed to offer
similar advantages over open surgery to those for percutaneous native bladder surgery. Stone recurrence after
successful removal has been reported to be 10-42% [842, 843], but appears to be unrelated to the modality
used for stone removal [809, 815, 819, 820, 822, 827].

Figure 6.1 Management of Bladder stones
Bladder stone diagnosed on

imaging or cystoscopy
Investigations for cause:

• physical examination
X-ray KUB
• uroflowmetry and post-void
residual
• urine dipstick (inc. pH±
culture)
• serum tests
In selected patients, consider:
• upper tract imaging (if history Radio-lucent
of urolithiasis or loin pain) (or other factors
Radio-opaque
• cysto-urethroscopy or suggesting uric
urethrogram acid calculi)
Consider concomitant treatment Surgical Treatment:

Offer oral
for: 1. TUCL*
chemolitholysis††
• BOO 2. PCCL*
• Chronic urinary retention If TUCL is not possible or
(e.g., intermittent self- advisable (e.g., urethral
catheterisation) stricture, young child)
• Pre-disposing metabolic 3. Open cystolithotomy†
factors Consider as first-line
Ultrasound
treatment in selected cases,
e.g., very large stones
4. SWL, laparoscopic
cystolithotomy
Stone analysis** Failure Success
BOO = Bladder Outlet Obstruction, TUCL = Trans-urethral cystolithotripsy, PCCL = Percutaneous

cystolithotripsy, SWL = Shock-wave Lithotripsy.
* Lithotripsy modality at surgeon’s discretion (e.g., mechanical, laser, pneumatic, ultrasonic).

† Prefer “tubeless” procedure (without placing a catheter or drain) for children with primary bladder stones and
no prior infection, surgery, or bladder dysfunction where open cystolithotomy is indicated.

** Stone analysis should be sent for all first-time stone formers and in patients who develop a recurrence under
pharmacological prevention, early recurrence after interventional therapy with complete stone clearance or
late recurrence after a prolonged stone-free period (see main Urolithiasis guideline).
†† Use an alkaline citrate or sodium bicarbonate with frequent urine pH monitoring and dose titration to achieve
a consistent pH > 6.5.
6.5 Bladder stones follow-up

There are no studies examining the merits of differing follow-up modalities or frequencies following
conservative, medical, or operative treatment of bladder stones in adults or children. Identification and
prevention of the cause of bladder stone formation will be crucial to prevent recurrence (see section 6.3.2
Diagnosing the cause of bladder stones).
In adults, there is a paucity of evidence on dietary modification or medical treatment for the prevention of
bladder stone recurrence. Recommendations in the EAU Guideline on Urolithiasis, based on evidence from
upper tract stones, constitutes the best available recommendations, especially for migratory bladder stones
(see Section 4 Metabolic Evaluation and Recurrence Prevention4) .

Where it is possible to address the cause of secondary bladder stones (e.g., treatment of BPO), it is unclear
whether metabolic intervention would offer any significant additional benefit in preventing stone recurrence.
However, especially where the secondary cause cannot be addressed (e.g., indwelling catheter, neuropathic
bladder, bladder augmentation or urinary diversion); metabolic interventions are likely to reduce bladder stone
recurrence rates.
Regular bladder irrigation reduces the chances of bladder stone recurrence in adults and children with bladder
augmentation or continent cutaneous urinary diversion and adults with spinal cord injury who perform CISC
(see section 6.4.5 Special Situations) [800, 805, 830].
In children with primary (endemic) bladder stones maintenance of hydration, avoidance of diarrhoea and a
mixed cereal diet with milk and Vitamins A and B supplements, with the addition of eggs, meat, and boiled
cows’ milk after one year of age are recommended to prevent recurrence [758].
Finally, there are contradictory reports on a possible association between bladder calculi and future
development of bladder cancer [844-846]. The need for follow-up with regular cystoscopy therefore remains
controversial.
6.6 Summary of evidence and recommendations for the treatment of bladder stones
The incidence of bladder stones peaks at three years in children (endemic/primary stones in 2c
developing countries) and 60 years in adults.
The aetiology of bladder stones is typically multi-factorial. Bladder stones can be classified as primary 4
(endemic), secondary (associated with lower urinary tract abnormalities e.g., BPO, neuropathic
bladder, foreign body, chronic bacteriuria) or migratory (having formed in the upper tract).
In adults, BOO is the most common pre-disposing factor for bladder stone formation. 2c
Of men undergoing surgery for BPO, 3-4.7% form bladder stones. 2b
Metabolic abnormalities are also likely to contribute to bladder stone formation in patients with 2b
secondary bladder stones.
Primary (endemic) bladder stones typically occur in children in areas with poor hydration, recurrent 5
diarrhoea, and a diet deficient in animal protein. The following measures are proposed to reduce their
incidence: maintenance of hydration, avoidance of diarrhoea, and a mixed cereal diet with milk and
Vitamins A and B supplements; with the addition of eggs, meat, and boiled cows’ milk after one year
of age.
In adults, US has a sensitivity of 20-83% for diagnosing bladder stones. 2b
In adults, X-ray-KUB has a sensitivity of 21-78%; sensitivity increases with stone size. 2b
Computed tomography has a higher sensitivity than US for the detection of bladder stones. 2b
Cystoscopy has a higher sensitivity than X-ray-KUB or US for the detection of bladder stones. 2b
Endoscopic bladder stone treatments (trans-urethral or percutaneous) are associated with comparable 1a
SFRs, but a shorter length of hospital stay, duration of procedure and duration of catheterisation
compared to open cystolithotomy in adults.
Stone-free rates are lower in patients treated with SWL than those treated with open or endoscopic 2a
procedures in both adults and children.
Transurethral cystolithotripsy is associated with a shorter length of hospital stay, less pain and a 1b
shorter convalescence period than percutaneous cystolithotripsy in adults.
Transurethral cystolithotripsy with a nephroscope is quicker than when using a cystoscope with no 1a
difference in SFR in adults.
Transurethral cystolithotripsy with a resectoscope is quicker than when using a cystoscope with no 2a
difference in SFR in adults.
Mechanical, pneumatic and laser appear equivalent lithotripsy modalities for use in endoscopic 2a
bladder stone treatments in adults and children.
Open cystolithotomy without a retropubic drain or urethral catheter (“tubeless”) is associated with a 2b
shorter length of hospital stay than traditional cystolithotomy and can be performed safely in children
with primary stones and no prior bladder surgery or infections.

Bladder stone removal with concomitant treatment for BOO is associated with no significant 2b
difference in major post-operative complications when compared to BOO treatment alone in adults.
However, concomitant bladder stone treatment does increase the rates of short-term post-operative
incontinence and UTI.
The incidence of bladder stone formation in spinal cord injury patients is 19-67% over time. The 2b
absolute annual risk of stone formation in spinal cord injury patients is significantly higher with an
indwelling catheter compared to those voiding with CISC or spontaneously.
The incidence of bladder stone formation after bladder augmentation or vesico-entero-cystostomy is 2b
between 2-53% in adults and children.
Urinary diversion including orthotopic ileal neobladders, ileocaecal continent cutaneous urinary 2b
diversion and rectosigmoid reservoirs is associated with urinary reservoir stone formation in 0-43%.
The risk of bladder stone formation in spinal cord injury, bladder augmentation or continent urinary 2b
diversion patients is reduced by performing regular bladder irrigation.

Use ultrasound (US) as first-line imaging with symptoms suggestive of a bladder stone. Strong
Use cystoscopy or computed tomography (CT), or kidney-ureter-bladder X-Ray (KUB) to Strong
investigate adults with persistent symptoms suggestive of a bladder stone if US is negative.
Use X-Ray KUB for adults with confirmed bladder stones to guide treatment options and Weak
follow-up.
All patients with bladder stones should be examined and investigated for the cause of Weak
bladder stone formation, including:
• uroflowmetry and post-void residual;
• urine dipstick, pH, ± culture;
• metabolic assessment and stone analysis (see sections 3.3.2.3 and 4.1 of the
Urolithiasis guidelines for further details).
In selected patients, consider:
• upper tract imaging (in patients with a history of urolithiasis or loin pain);
• cysto-urethroscopy or urethrogram.
Offer oral chemolitholysis for radiolucent or known uric acid bladder stones in adults. Weak
Offer adults with bladder stones transurethral cystolithotripsy where possible. Strong
Perform transurethral cystolithotripsy with a continuous flow instrument in adults (e.g., Weak
nephroscope or resectoscope) where possible.
Offer adults percutaneous cystolithotripsy where transurethral cystolithotripsy is not Strong
possible or advisable.
Suggest open cystolithotomy as an option for very large bladder stones in adults and Weak
children.
Offer children with bladder stones transurethral cystolithotripsy where possible. Weak
Offer children percutaneous cystolithotripsy where transurethral cystolithotripsy is not Weak
possible or is associated with a high risk of urethral stricture (e.g., young children, previous
urethral reconstruction, and spinal cord injury).
Open, laparoscopic, and extracorporeal shock wave lithotripsy are alternative treatments Weak
where endoscopic treatment is not advisable in adults and children.
Prefer “tubeless” procedure (without placing a catheter or drain) for children with primary Weak
bladder stones and no prior infection, surgery, or bladder dysfunction where open
cystolithotomy is indicated.
Individualise imaging follow up for each patient as there is a paucity of evidence. Weak
Factors affecting follow up will include:
• whether the underlying functional predisposition to stone formation can be treated (e.g.,
TURP);
• metabolic risk.
Recommend regular irrigation therapy with saline solution to adults and children with Weak
bladder augmentation, continent cutaneous urinary reservoir or neuropathic bladder
dysfunction, and no history of autonomic dysreflexia, to reduce the risk of stone recurrence.

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8. CONFLICT OF INTEREST
All members of the Urolithiasis Guidelines Panel have provided disclosure statements of all relationships that
they have that might be perceived as a potential source of a conflict of interest. This information is publicly
accessible through the European Association of Urology website: http://www.uroweb.org/guidelines/. This
guidelines document was developed with the financial support of the European Association of Urology. No
external sources of funding and support have been involved. The EAU is a non-profit organisation and funding
is limited to administrative assistance and travel and meeting expenses. No honoraria or other reimbursements
have been provided.

9. CITATION INFORMATION
The format in which to cite the EAU Guidelines will vary depending on the style guide of the journal in which the
citation appears. Accordingly, the number of authors or whether, for instance, to include the publisher, location,
or an ISBN number may vary.
The compilation of the complete Guidelines should be referenced as:

EAU Guidelines. Edn. presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-19-6.
If a publisher and/or location is required, include:

EAU Guidelines Office, Arnhem, The Netherlands. http://uroweb.org/guidelines/compilations-of-all-guidelines/
References to individual guidelines should be structured in the following way:

Contributors’ names. Title of resource. Publication type. ISBN. Publisher and publisher location, year.


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© European Association of Urology 2023

2 UROLITHIASIS - LIMITED UPDATE MARCH 2023

4. METABOLIC EVALUATION AND RECURRENCE PREVENTION 39

UROLITHIASIS - LIMITED UPDATE MARCH 2023 3

4 UROLITHIASIS - LIMITED UPDATE MARCH 2023

8. CONFLICT OF INTEREST 118

9. CITATION INFORMATION 119

UROLITHIASIS - LIMITED UPDATE MARCH 2023 5

1.2 Panel composition

1.3 Available publications

1.4 Publication history and summary of changes

1.4.2 Summary of changes

Recommendation Strength rating

6 UROLITHIASIS - LIMITED UPDATE MARCH 2023

2.3 Future goals

UROLITHIASIS - LIMITED UPDATE MARCH 2023 7

3.1.2 Stone composition

Table 3.2: Stone composition

3.1.3 Risk groups for stone formation

8 UROLITHIASIS - LIMITED UPDATE MARCH 2023

UROLITHIASIS - LIMITED UPDATE MARCH 2023 9

Table 3.5 Risk factors for CKD and renal stones

3.2 Classification of stones

10 UROLITHIASIS - LIMITED UPDATE MARCH 2023

3.2.2 Stone location

3.2.3 X-ray characteristics

Table 3.7: X-ray characteristics

3.3 Diagnostic evaluation

3.3.1.1 Evaluation of patients with acute flank pain/suspected ureteral stones

UROLITHIASIS - LIMITED UPDATE MARCH 2023 11

Recommendations Strength rating

3.3.2 Diagnostics - metabolism-related

3.3.2.1 Basic laboratory analysis - non-emergency urolithiasis patients

3.3.2.2 Analysis of stone composition

In clinical practice, repeat stone analysis is needed in the case of:

Recommendations Strength rating

12 UROLITHIASIS - LIMITED UPDATE MARCH 2023

3.3.3 Diagnosis in special groups and conditions

Recommendations Strength rating

3.3.3.2 Diagnostic imaging in children

UROLITHIASIS - LIMITED UPDATE MARCH 2023 13

Plain films (KUB radiography)

Non-contrast-enhanced computed tomography

Magnetic resonance urography

3.3.3.2.1 Summary of evidence and recommendations for diagnostic imaging in children

Recommendations Strength rating

3.4 Disease Management

3.4.1 Renal colic

14 UROLITHIASIS - LIMITED UPDATE MARCH 2023

Prevention of recurrent renal colic

Recommendations Strength rating

3.4.2 Management of sepsis and/or anuria in obstructed kidney

UROLITHIASIS - LIMITED UPDATE MARCH 2023 15

Recommendations Strength rating

3.4.3 Medical expulsive therapy

3.4.3.1 Summary of evidence and recommendations for MET

16 UROLITHIASIS - LIMITED UPDATE MARCH 2023

Recommendation Strength rating

3.4.4.1 Summary of evidence and recommendations for chemolysis

Recommendations (oral chemolysis of uric acid stones) Strength rating

3.4.5 Extracorporeal shock wave lithotripsy (ESWL)