Kuliah Nefrologi Anak

Mahasiswa FK Undip

dr. HR Rochmanadji Widajat SpA(K),MARS

dr. Muhammad Heru Muryawan,SpA
dr. Omega Mellyana SpA
September 2012
Pokok bahasan
1. Glomerulopati
1. Sindrom nefrotik
2. Glomerulonefritis
2. Gagal ginjal
1. Acute Kidney Injury (AKI)/ Gagal Ginjal Akut
2. Chronic Kidney Disease (CKD)/ Gagal Ginjal Kronik
3. Hipertensi
4. InfeksiSaluran Kemih
 1.Glomerulopathy

Sindrom nefrotik Glomerulonefritis

 GLOMERULOPATHY
MAIN CAUSE OF KIDNEY FAILURE IN CHILDREN

DEFINITION: inflamatory changes in glomerulus due

to immunologic mechanism

CLINICAL MANIFESTATIONS
Isolated proteinuria
Proteinuria + edema (i.e.Nephrotic syndrome)
Isolated haematuria
Hypertension +/- proteinuria/haematuria
Renal failure
 Classification
Alport Syndrome
Congenital Congenital Nephrotic Syndrome

1. Minimal change (MCNS)

2. Focal segmental
glomerulosclerosis
Primary/
3. Mesangial proliferative
idiopathic glomerulonephriti
4. Membrano-proliferative
glomerunephritis
Acquired 5. Membranous glomerulonephritis
6. IgA Nephropathy
7.
Glomerulonephritis
POST INFECTION others
POSTSTREPTOCOCCAL
Secondary GLOMERULONEPHRITIS
MULTISYSTEM DISEASES : LE, HUS
INTOXICATION: drugs, metal
NEOPLASMS
 Nephrotic Syndrome
NEPHROTIC SYNDROME is defined as
A clinical state characterized by the combination of
- heavy proteinuria
- hypoproteinaemia
- oedema
- hyperlipidaemia

Heavy proteinuria : > 50 mg/kg BW/day or >40mg/m22/h

creatinine/protein ratio > 2 mg/mg
selective proteinuria

Hypoalbuminaemia : < 2.5 g/dl

Hyperlipidaemia : variable degree

invariably present
Epidemiology
Incidence
Incidence 2-7 new cases per 10,000
Prevalence 15.7 cases per 10,000
Age
MCD 2.5 years median age
FSGS 6 years median age
Sex
3:2 Boys; Girls in children <6 yo
Equal ratio in those older
Classification

1. CONGENITAL NEPHROTIC SYNDROME

2. IDIOPATHIC NEPHROTIC SYNDROME

3. SECONDARY NEPHROTIC SYNDROME

 CONGENITAL NEPHROTIC SYNDROME
clinical onset in the first 3 months of life
proteinuria in utero or at birth

elevated amniotic fluid level of alpha-

fetoprotein
before 20 weeks gestation
Classification :
Primary
Finnish type
Diffuse mesangial sclerosis

Minimal changes NS

Focal segmental glomerulosclerosis

Secondary
congenital syphilis, toxoplasmosis,

cytomegalovirus
XY gonadal dysgenesis and Wilms tumour

nephroblastoma
CONGENITAL NEPHROTIC SYNDROME
the majority of cases

the Finnish type

2 autosomal recessive inheritance
2 incidence in Finland: 12 cases/100 000 births
2 born prematurely 35-38 weeks
2 small for gestational age
2 placenta weighing > 25% birth weight
2 breech presentation, fetal asphyxia
2 widened cranial sutures, large fontanelles, pliable
cartilagenous tissue
2 small nose, wide-set eyes, low-set ears

Prognosis : infaust
 SECONDARY NEPHROTIC SYNDROME
Causes of secondary nephrotic syndrome

1. Extrinsic antigens, drugs, Penicillamine Gold

Mercury Trimethadione
and toxins Probenecid Volatile hydrocarbon
Bees sting snake venom

Hepatitis B Syphilis
2. Infections Malaria Filariasis
Leprosy Schistosomiasis

Lupus erythematosus Syorgens syndrome

3. Intrinsic antigens Sarcoidosis Renal tubular antigen
Transplantation vasculitis syndrome

4. Neoplasms Carcinoma Lymphoma

Leukemia

5. Associations, possibly doubtful Diabetes mellitus Renal vein thrombosis

Rheumatoid arthriris Sickle cell disease
Guillan Barre synd.
PATHOPHYSIOLOGY

1.PROTEINURIA
2.PERMEABILITY IMPAIRMENT
MOLECULE IONIC CHARGE
MOLECULE SIZE
Glomerular Capillary Membranes
Mechanism of Proteinuria

A SIZE-SPECIFIC BARRIER
A CHARGE-SPECIFIC BARRIER
 CLINICAL MANIFESTATIONS
Oedema (uptill 40% BW), ascites, hydrothorax,
scrotal oedema
Secondary infections : skin, peritonitis
Anaemia
Growth disturbances
Tetany (hypocalcaemia)
Hypovolemic shock
Vein thrombosis
Acute renal failure: oliguria/anuria,
metabolic acidosis,potassium
Nephrotic syndrome

Generelised edema
(anasarca)
Older child with
nephrotic syndrome

Pitting peripheral
oedema
Nephrotic Syndrome

Ascites
Nephrotic syndrome

SCROTAL EDEMA LABIAL EDEMA

LABORATORY FINDINGS

Urinary analysis:
specific gravity , pH
proteinuria massive
(selective - albumin 85-95%)
qualitative/semiquantitative > 2+
quantitative : Esbach
leukocyturia
haematuria
double refractile lipoid bodies
hyaline cast

Plasma :
Hb , Ht
hypoalbuminaemia, reverse ratio alb/glob
hypercholesterolaemia
normal: ureum, creatinine
 IDIOPATHIC NEPHROTIC SYNDROME

The Morphologic Spectrum of primary nephrotic

syndrome (Churg, Habib & White, 1970)

1. Minimal change
2. Focal segmental glomerulosclerosis
3. Proliferative glomerulonephritis
Mesangial
With crescent formation

Focal

Diffuse exudative

Mesangiocapillary (membrano-proliferative)

4. Membranous glomerulonephritis
5. Advance chronic glomerulonephritis
EPIDEMIOLOGY
 TREATMENT

1. Medication
1. STEROID
2. DIURETICS
3. IMMUNOSUPRESSIVE AGENTS
2.Dietary (nephrotic diet)
LOW SALT (1-2 g/day)
PROTEIN 2-3 g/kg/day
3. OPTIMIZING CONDITION
(physic,psychology,social)
- Activity : not limited
- Immunization: as scheduled
- Psychological support : the child + parents

FOLLOW UP
OUT PATIENT CLINIC:
- Symptomatic : weekly - monthly
- Asymptomatic : every 3-6 months (renal
function evaluation)

ADMISSION :
generelized oedema, severe hypertension,
severe infection, shock, acute renal failure
 STANDARD TREATMENT
CORTICOSTEROID (PREDNISON)

INITIAL TREATMENT

FULL DOSE ALTERNATING

4 MINGGU 4 MINGGU
Prednison FD: 60 mg/m 2/day
Prednison AD: 40 mg/m 2/day

REMISSION (+) REMISSION (-) STEROID

SENSITIVE

STEROID RESISTANT

IMMUNOSUPRESSIVE AGENTS

THE INTERNATIONAL COMMITTEE OF KIDNEY DISEASE IN CHILDREN (1967)

RECOMMENDED DOSAGES
PREDNISON
DAILY : 60 mg/m2/day in 3 divided dose
Intermittent : 40 mg/m2/day in 3 divided dose,
3 executive days in a week
Alternatively: 35 mg/m2/day single dose

CICLOPHOPHAMIDE
2-3 mg/kg/day for 8 12 weeks in combination with
steroid intermittent

CHLORAMBUCILE
0,1-0,2 mg/kg/day in divided dose with steroid AD
Definitions
Remission
Urinary protein < 4 mg/ m2hr or Albustix = 0/Trace
for 3 consecutive days
Steroid Responsive
Remission with steroids alone
Relapse
Urinary protein > 40 mg/m2*hr or Albustix > 2+
for 3 consecutive days
Frequent Relapses
Two or more relapses within 6 months of initial
response or 4 or more relapses within any 12
month period
Steroid Dependence
Two consecutive relapses occurring during
corticosteroid treatment or within 14 days of its
cessation
Steroid Resistance
Failure to achieve response in spite of 4 weeks of
prednisone 60 mg/m2*day
THE CLINICAL RESPONS OF MINIMAL CHANGES
PATIENTS TO STEROID (ISKDC)

Minimal Change 100%

Responsive 93% Early Non responsive 7%

No- Infrequent Frequent Late responsive Non-responsive

relaps Relapser Relapser 5% 2%
36% 18% 39%

Non responsive
5%

(Kidney Int. 13-43, 1978)

PROGNOSIS

RENAL FUNCTION gradually

failure

rapid, about 5
10 years
SECONDARY
GLOMERULONEPHRITIS
 DEFINITION

ACUTE POST INFECTION GLOMERULONEPHRITIS

IMMUNOLOGICAL REACTIONS IN KIDNEY

UPON EXTRA RENAL INFECTION
CAUSED BY AGENTS

The most common :

Extra renal infection with group A beta-hemolytic
streptococci

ACUTE POST STREPTOCOCCAL

GLOMERULONEPHRITIS
 EPIDEMIOLOGIC CHARACTERISTICS

Actual incidence hard to ascertain

large % of cases : subclinical in nature

Developing countries : a common form of GN in children

the disease is self-limited in most

Advent of antibiotics and better public health

influence incidence
ACUTE POSTSTREPTOCOCCAL GLOMERULONEPHRITIS
(APSGN)

NEPHRITOGENIC STRAINS OF STREPTOCOCCI

GROUP A
Beta-hemolytic
Respiratory tract M 1,2,4,12,18,25
Skin M 49, 55, 57, 60

GROUP C
Streptococci
Streptococcus zooepidermicus

Site of infection:
upper respiratory tract: pharynx, tonsilles, middle ear
skin
 Upper Respiratory
Sore Throat
Tonsillar exudate
Fever
Chills
20% school children
carriers
Skin
Impetigo
Lesions on
extremities
Commonly on face
Pustular and crusty
INFECTIONS PRECEDING ACUTE GN
BACTERIAL
Group A, Beta-hemolityc streptococci
Streptococcus viridans
Streptococcus pneumoniae
Streptococcus grup C (Streptococcus zooepidermicus)
Staphylococcus aureus
Staphylococcus epidermidis
Salmonella typhosa
Gonococcus
Mycoplasma
Staphylococcus albus
Treponema pallidum
Corynebacterium bovis
Klebsiella pneumoniae
Diplococcus pneumonia
Brucella suis
Meningococcus
Leptospira
Propionibacterium acnes
Mycobacterium leprae
Actinobacillus
INFECTIONS PRECEDING ACUTE GN
VIRAL
Varicella-zantu - Coxsackie B
Rubella - Echovirus
Cytomegalovirus - Enterovirus
Epstein-Barr - Picornavirus
Hepatitis B - Onconavirus
Measles - Influenza
Mumps - HIV

PARASITIC
Plasmodium falsiparum - leishmanias
Plasmodium malariae - tripanosomes
Toxoplasma gondii - trichinosis
Schistosoma mansoni - filaria

FUNGAL RICKETSIAL
Coccidiodes immitus - Scrub typhus
ASSOCIATION BETWEEN
AGN STREPTOCOCCI INFECTION

1. Following scarlet fever

2. Group A, -streptococcus hemolytic has been isolated
3. ASTO

Latent period
# pharyngitis associated : 10 d
# impetigo associated : 21 d
Pathogenesis
HYPOTHESIS:

CIRCULATING IMMUNE COMPLEX

FORMATION
IN SITU IMMUNE COMPLEX FORMATION
AUTOIMMUNE PROCESS
Neuraminidase produced by streptococci alters
endogenous IgG and makes it autoantigenic
altered IgG form circulating complexes
deposited in kidney
CLINICAL MANIFESTATIONS
A. ACUTE
B. SUB ACUTE (RAPIDLY PROGRESSIVE)
C. CHRONIC
 CLINICAL MANIFESTATIONS

Various (subclinical mild - severe)

Sudden onset of painless gross hematuria
(coke- or tea-colored urine)
- Oedema (puffy eyes - generalized)
Oliguria / anuria
Acute renal failure
Hipertension
hypertensive encephalopathy :
headache,vomiting, lethargy, confusion, seizures
Congestive heart failure or pulmonary edema
Anaemia
FREQUENCY OF CLINICAL MANIFESTATIONS IN APSGN

Gross hematuria 25 33 %
Volume overload
oedema 85 %
hipertension 60 80 %
circulatory congestion 20 %
CNS symptoms 10 %
 LABORATORY FEATURES
URINALYSIS :
proteinuria 1 - 4+
hematuria
abnormal sediment:
dysmorphic RBCs, WBCs, cellular casts,
granular casts, RBC casts
SERUM :
- BUN/ureum , creatinine
- K , acidosis, hyperphosphatemia, Ca
- Hypocomplementemia
in first week, normal in 8 10 wks
- Properdin level
- Evidence of a recent streptococcal infection
antistreptozyme, ASO, antihyaluronidase, anti-
DNase B
Clinical and laboratory evaluation in acute GN

History (sore throat, impetigo)

Physical examination (blood pressure, fluid overload)
Urinalysis, 24-h urine for protein and creatinine
Throat culture, skin lesion culture
Blood chemistry : serum electrolytes, ureum, creatinine,
Ca, P, total proteins, albumin, cholesterol
Serum complement (CH50, C3, C4)
Serum for anti streptococcal antibodies

Antinuclear antibody test

Antiglomerular basement membrane and antineutrophil
cytoplasmic antibodies in patient presenting with
rapidly progressive GN
Renal biopsy (if unresolved)
 PATHOLOGY ANATOMY

Light microscopy
DIFFUSE ENDOCAPILLARY PROLIFERATIVE
GLOMERULONEPHRITIS
- diffuse mesangial cell and matrix proliferation
- endothelial cell proliferation
- infiltration polymorphonuclear cells and monocytes
- occlusion capillary lumens

Immunofluorescence microscopy
irregular fine coarse granular staining in mesangium
and along capillary loop for IgG, C3, IgM, IgA,

Electron microscopy
- electron-dense deposits in mesangium
- HUMPS (large deposits in subepithelial location)
pathognomonic
 DIAGNOSIS
Sudden onset of gross hematuria, oedema, hypertension
and acute renal failure following a recent streptococcal infection

Urinalysis findings characteristic of GN

Laboratory evidence of a recent streptococcal infection

Low serum complement

DIFFERENTIAL DIAGNOSIS
IgA Nephropathy synpharyngetic hematuria
Associated with systemic disease
Chronic glomerulonephritis
TREATMENT (1)

1. Bed rest
2. Antibiotic for eradicating streptococci
- Procain Penicillin 10 days
- Erythromicyn
3. Dietetic (fluid & salt restriction)
- low protein 1 g/kgBW/day
- low salt 1 g/day
- IVFD as necesarry
4. Prolonged anuria dialysis
- peritoneal dialysis
- haemodialysis
TREATMENT (2)

5. Diuretics
Furosemide 1 mg/kgBW/dose 2x/ day

6. Symptomatic treatment
hypertension
hypertensive encephalopathy
congestive heart failure
acute renal failure
TREATMENT (3)
Treatment of hypertension associated with APSGN

Mild Severe

Diuretics furosemide furosemide i.v.

i.v. or p.o.

Vasodilators hydralazine diazoxide i.v.

Na-nitroprusside i.v.

Ca-channel blocker nifedipine p.o. Nifedipin sublingual

ACE inhibitor captopril p.o.

Evaluation to Document Likelihood of Typical
APSGN (1)
1 . Typical of presentation with no findings suggestive
of other systemic disease

2. Evidence of prior streptococcal infection

a. Throat or skin lession culture positive for streptococci
b. Elevated antibody titers

3. Complement abnormalities typical

a. Decreased CH50 and C3 during acute phase
b. C4 usually normal
c. Levels rise toward normal by 6-8 wks
Evaluation to Document Likelihood of Typical
APSGN (2)

4. Beginning recovery in 1 week

a. Diuresis
b. Blood pressure normalize
c. BUN, creatinine begin to fall

5. Normalization of urine sediment

d. Resolution of gross hematuria by 2-3 weeks
e. Resolution of proteinuria by 3-6 months
f. Resolution of microscopic hematuria by 1 year
RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

A clinicopathologic entity

Rapidly deteriorating renal function

PA : diffuse glomerular epithelial crescent formation
(crescentic glomerulonephritis)

Clinical manifestations:
similar to APSGN severe
rapidly deteriorating

Management:
steroid / immunosupressive agents : controversial
CHRONIC GLOMERULONEPHRITIS (1)

Haematological abnormalities persist

Proteinuria

Acute exacerbation of chronic glomerulonephritis

Evidence of chronicity of disease

anaemia,
abnormal growth pattern,
exacerbation of acute nephritic syndrome
CHRONIC GLOMERULONEPHRITIS (2)

Mightbe asymptomatic renal failure

Mild oedema , subfebrile temperature

NEPHROTIC STAGE OF GLOMERULONEPHRITIS

a predominant picture of nephrotic syndrome

- clear oedema
- reverse ratio of albumin/globulin
- hypercholesterolemia

Renal function progressively

CHRONIC GLOMERULONEPHRITIS (3)

Laboratory findings
Urine : isostenuria
proteinuria
hematuria
leukocyturia

Serum: ureum , creatinine

K, Ca , P

anaemia : normochrom normocytic

CHRONIC GLOMERULONEPHRITIS (4)

PATHOLOGY ANATOMY
MACROSCOPICALLY
- SHRINKED KIDNEY
- CONTRACTED KIDNEY

MICROSCOPICALLY
- HYALINE DEGENERATION
- TUBULUS ATROPHY
- NEPHRON REPLACED WITH FIBROID TISSUE
+ LYMPHOCYTE INFILTRATION
TREATMENT STRATEGY FOR ACUTE GLOMERULONEPHRITIS

1. Bed rest as necessary

2. Fluid and salt restriction
3. Specific intervention for
a. Hypertension and other sign of volume overload
b. Hyperkalemia
c. Acidemia
d. Hyperphosphatemia

4. Confirm likelihood of poststreptococcal disease

5. Watch for onset of recovery within 7 days
6. Keep high index of suspicion for diseases other
than APSGN
 NEPHRITIC OEDEMA NEPHROTIC OEDEMA

Renal and water retention Alteration of Starling forces

(capillary osmotic pressure )

Expansion of circulatory volume Oedema formation

Alteration of Starling forces Volume contraction

(capillary hydraulic pressure )

Oedema formation Renal and water retention

 EFFECTIVE CIRCULATORY VOLUME

Renal perfusion Volume receptors

Internal Sympathetic AVP ANP ?

PRA
factors activity

Angiotensin II

Aldosterone Alterations of Renal nerve activity

peritubular Starling
forces

Distal Na Proximal Na Water

reabsorption reabsorption reabsorption

Sodium and water retention

PRA =plasma renin activity; AVP = arginine vasopressin; ANP=atrial natriuretic peptide