Dr.

Dhian Endarwati,SpA
Maret 2017
• Sindrom nefrotik • Glomerulonefritis
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 glomerulonephriti
4. Membrano-proliferative glomerunephritis
idiopathic
5. Membranous glomerulonephritis
6. IgA Nephropathy
7. Glomerulonephritis others
Acquired
• POST INFECTION – POSTSTREPTOCOCCAL
GLOMERULONEPHRITIS
Secondary • MULTISYSTEM DISEASES : LE, HUS
• INTOXICATION: drugs, metal
• NEOPLASMS
 Massive Proteinuria
(≥ 50 mg/kg body weight /day/ ≥ 40 mg/m2/hour /
urine protein/creatinin ratio > 2 mg/mg /
dipstick ≥ +2)

Hypoalbuminemia < 2,5 g/dL

Edema

Hyperlipidemia

Roth KS. Nephrotic syndrome: Pathogenesis and management. Ped in Rev 2002;23(7):237-47
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 of Nephrotic
syndrome
Response to
Histopathology:
steroid

Sensitive Minimal

Non minimal
Resistant  Mainly
FSGS
Barratt TM. Steroid responsive nephrotic syndrome. In: Barratt TM, editor. Pediatric nephrology. 4th edition. Baltimore:
Lippincot Wiliams & Wilkins;1999. p. 732.
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
 etc
CONGENITAL NEPHROTIC SYNDROME
 the majority of cases

 autosomal recessive inheritance

 incidence in Finland: 12 cases/100 000 births

 born prematurely 35-38 weeks

 small for gestational age

 placenta weighing > 25% birth weight

 breech presentation, fetal asphyxia

 widened cranial sutures, large fontanelles, pliable

cartilagenous tissue
 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
•Bee’s sting •snake venom

•Hepatitis B •Syphilis
2. Infections •Malaria •Filariasis
•Leprosy •Schistosomiasis

•Lupus erythematosus •Syorgen’s 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.
 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
MINIMAL DISEASE
PROLIFERATIVE DISEASE
MEMBRANOUS DISEASE
 Pathophysiology
The underlying pathogenetic
abnormality of NS is proteinuria
due to an increase in glomerular
capillary wall permeability.

1. The capillary wall loss the negative charge

glycoprotein barries
2. Increase glomerular permeability to proteins
Filtrasi Glomerulus
ULTRAFILTRASI Proses pembentukan ultrafiltrat plasma oleh glomerulus

Langkah I Melalui 3 barier:

pembentukan urin - Sel endotel
- Membran basalis
- Celah filtrasi dari podosit
ULTRAFILTRAT
Cairan bebas protein yg melalui ddg kapiler glomerulus
 mencapai ruang Bowman

Mengandung elektrolit, glukosa, fosfat, Ureum, Kreatinin,

Peptida, protein BM rendah, kec. albumin & globulin
Pathogenesis of nephrotic syndrome

Maintain
DAMAGED barrier
Proteinuria
function

McBryde KD. Pediatric steroid-resistant nephrotic syndrome. Curr Probl Pediatr.2001;31:275-307

Glomerular Capillary Membranes
Mechanism of Proteinuria

A SIZE-SPECIFIC BARRIER
A CHARGE-SPECIFIC BARRIER
 PROTEINURIA

- Transferine  IgG 
- Glob.Thyroxin  IgE 
- Glob. Vit. D  IgA 
- Coagulation factors  IgM 
F VII, IX, XII  Fibrinogen 

HYPOALBUMINAEMIA

B-lipoprot   hyperlipidaemia

ONCOTIC PRESSURE 
Lipiduria
OEDEMA
HYPOVOLAEMIA

Peripheral circulation collaps

Hb 
Death
Aldosteron  
 Packed cell vol 
Renal perfusion 
Na and H2O
retention  Viscocity 
 renin plasma  Ureum 
Vein thrombosis +
K
 Nephritic edema Nephrotic edema
Renal salt and water Alteration of Starling forces
retention (Capillary colloid osmotic
pressure )
Expansion of
circulatory volume Edema formation

Alteration of Starling forces Volume contraction

(Capillary hydraulic pressure )

Edema formation Renal salt and water

retention

Proposed scheme of edema formation in

patiens with glomerular disease
 Proteinuria

Hypoalbuminemia

Plasma oncotic pressure

Transudation of fluid from intravascular

compartment to the interstitial space (= edema)

Exacerbating
Release Decreasing edema
antidiuretic intravascular volume
hormone
Reabsorbed Na & H2O are
Renal perfusion lost in the interstitial space

Activating the Renin-Angiotensin-

Aldosteron system

Na distal tubular reabsorption

H2O Reabsorption in the collecting duct

Mechanism of edema formation in “Circulation underfilled” Theory

CLINICAL MANIFESTATIONS

Oedema (uptill 40% BW) : palpebrae, 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
 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, initial
attack nefrotik syndrome
 STANDARD TREATMENT
CORTICOSTEROID (PREDNISON)

INITIAL TREATMENT
FULL DOSE ALTERNATING

4 MINGGU 4 MINGGU
Prednison FD: 60 mg/m2/day
Prednison AD: 40 mg/m2/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
ACUTE POST STREPTOCOCCAL
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
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
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

- 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

a. Resolution of gross hematuria by 2-3 weeks
b. Resolution of proteinuria by 3-6 months
c. Resolution of microscopic hematuria by 1 year
THANK YOU !