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EAU Guidelines On Urolithiasis 2023
EAU Guidelines On Urolithiasis 2023
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
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
3.4.2.1 Summary of evidence and recommendations for the management of
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
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
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.
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.
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.
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.
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.
Furthermore, some specific kinds of urolithiasis also carry a particular risk of developing CKD/ESKD as shown
below.
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
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].
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]
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].
Summary of evidence LE
Only low-level data exist for imaging in pregnant women supporting US and MRI. 3
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
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.
Summary of evidence LE
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.
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
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].
3.4.1.1 Summary of evidence and recommendations for the management of renal colic
Summary of evidence LE
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.
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
Summary of evidence LE
For decompression of the renal collecting system, ureteral stents and percutaneous nephrostomy 1b
catheters are equally effective.
Summary of evidence LE
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.
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].
Summary of evidence LE
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.
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].
Post-treatment management
Mechanical percussion and diuretic therapy can significantly improve SFRs and accelerate stone passage after
SWL [200-203].
Summary of evidence LE
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.
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].
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].
Randomised prospective trials have found that routine stenting after uncomplicated URS (complete stone
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
Summary of evidence LE
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.
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).
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].
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].
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
Summary of evidence LE
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.
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].
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 3.10: 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).
Summary of evidence LE
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.
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].
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).
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].
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].
Summary of evidence LE
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
Figure 3.1: Treatment algorithm for ureteral stones (if active stone removal is indicated)
1. URS
> 10 mm
2. SWL
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].
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
Summary of evidence LE
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
Kidney stone
(all but lower pole stone 10-20 mm)
1. PNL
> 20 mm
2. RIRS or SWL
1. SWL or RIRS
< 10 mm
2. PNL
No SWL or Endourology*
Unfavourable
10-20 mm factors for SWL
(see section 3.4.5)
1. Endourology*
Yes 2. SWL
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].
Summary of evidence LE
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
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].
Summary of evidence LE
To detect residual fragments after SWL, URS or PNL, deferred imaging is more appropriate than 3
immediate imaging post intervention.
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
Summary of evidence LE
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
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
Summary of evidence LE
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.
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.
Summary of evidence LE
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
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
Summary of evidence LE
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.
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].
For diagnostic procedures see Section 3.3.3.2, for acute decompression see Section 3.4.2. and for metabolic
evaluation see Chapter 4.
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].
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
3.4.15.8 Summary of evidence and recommendations for the management of stones in children
Summary of evidence LE
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
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.
Table 3.12 shows the EAU Urolithiasis guidelines panel recommended protection methods to reduce radiation
exposure to patients, surgical, anaesthesiologic and nursing staff.
Figure 4.1: Assignment of patients to low- or high-risk groups for stone formation
STONE
Investigating a patient
Basic evaluation
with unknown
(Section 3.3.2.3)
composition (Table 3.1)
Specific metabolic
evaluation
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.
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.
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.
4.2.2 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].
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].
Summary of evidence LE
Increasing water intake reduces the risk of stone recurrence. 1a
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
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.
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
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
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
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)
Summary of evidence LE
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
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.
Calcium phosphate
stones
Carbonate
apatite Brushite stones
stones
Hydrochlorothiazide* Hypercalciuria
initially 25 mg/d Exclude RTA Exclude UTI > 8 mmol/d
up to 50 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
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].
4.5.3 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
Summary of evidence LE
Thiazide is beneficial in case of hypercalciuria. 1a
4.6.3.1 Summary of evidence and recommendation for the management of primary hyperoxaluria
Summary of evidence LE
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
Urinary pH
constantly > 5.8
Ammonium chloride
loading test**
(NH4CI 0.1 g/kg body weight)
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).
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.
4.6.5.1 Summary of evidence and recommendations for the management of tubular acidosis
Summary of evidence LE
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
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.
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].
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
Ammonium
Urate acid stone
urate stones
Hyperacidic Urine
Hyperuricosuria
urine pH < 5.5 pH > 6.5
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
Summary of evidence LE
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
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].
Summary of evidence LE
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
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
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].
Cystine Stones
Basic evaluation
4.9.3 Summary of evidence and recommendations for the management of cystine stones
Summary of evidence LE
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.
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
4.13.1 Recommendations for investigations for the assessment of patients with stones of unknown
composition [21, 27, 68, 627]
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
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].
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
* Not enough data about subgroup analysis of radiolucent and radiopaque stones.
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
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].
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].
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].
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.
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].
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].
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].
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].
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
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.
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.
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].
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) .
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
Summary of evidence LE
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.
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.