Dr.
Rai Muhammad Asghar
Associate Professor Pediatrics
Head of Pediatric Department
RMC Rawalpindi
Nephrotic
Syndrome
DEFINATION
Massive Proteinuria (>40mg/m2/hr)
Hypoalbuminemia (< 2.5 g/dl)
Edema
Hypercholesterolemia (>250mg/dl)
Epidemiology
15 times more common in children than adults
Incidence is 2-3/ 100,000 children per year
Etiology
Primary or Idiopathic- 90%
1. Minimal change disease 85%
2. Focal segmental glomerulosclerosis 10%
3. Mesangial proliferative Glomerulonephritis 5%
Secondary- 10%
a) Glomerulonephritis
Membranous Glomerulonephritis
Membranoproliferative Glomerulonephritis
b) Systemic Diseases
1. Systemic diseases
Henoch Schonlein Purpura
SLE
Diabetes mellitus
2. Infections
Hepatitis B,& C
Infective Endocarditis
Syphilis
Malaria
HIV
3. Drugs-
Penicillamine
Gold salts
Captopril
NSAID’s
4. Neoplasm's
Hodgkin’s lymphoma
Leukemia
Wilms tumor
PATHOPHYSIOLOGY
Permeability of glomerular capillary membrane Proteinurea
Hypoalbuminimia
Hepatic protein Plasma
synthesis including oncotic
lipoproteins. pressure.
Intravascular
volume
Hyperlipidemia Transudatio
n of fluid
ADH Renal
from
perfusio
intravascular
Water n
compartment
reabsorption pressure
to interstitial
in collecting Activate renin angiotensin space.
ducts aldosterone system
Tubular reabsorption of
Edema.
sodium & water↑
Pathophysiology
IDIOPATHIC NEPHROTIC SYNDROME
MINIMAL CHANGE DISEASE FOCAL
SEGMENTAL
SCLEROSIS
AGE 2-6yrs 2-10yrs
SEX 2:1 male [Link] male
HEMATURIA 10-20% 60-80%
HYPERTENSION 10% 20%
RENAL FAILURE No progression 10yrs
ASSOCIATIONS None None
SERUM CREATININ Inc. in 15-30% Inc. in 20-40%
IIMMUNOGENETICS HLA-B8, B12 None
LIGHT MICROSCOPY Normal Focal sclerosis
Negative
IMMUNOFLUORESCENCE IgM & C3 in lesions
ELECTRON MICRO Foot process fusion Foot process fusion
STEROID RESPONSE 90% 15-20%
SECONDARY NEPHROTIC SYNDROME
Clinical Features
Periorbital Puffiness
More marked is the morning
Edema later become generalized
Scrotal Edema
Plural effusion and Ascites is the late feature
Decrease urine output
Hypertension and Hematuria are absent
Clinical Features
Investigations
1. Urinalysis
Proteinuria 3+ or 4+
Urinary Protein excretion (>40mg/m2/hr)
Urinary Protein & Creatinine ratio > 3
Microscopic Hematuria 10%
Pus Cells : Underlying UTI
Cellular Casts: not in minimal change disease, common in other
forms
[Link]
Albumin < 2.5 g/dl
Cholesterol >250mg/dl
Normal C3
Normal renal function
[Link]
C.B.C. usually normal, ESR raised
Mantoux test to rule out TB
Chest X-Ray to rule out Pulmonary pathology or Pleural
effusion.
[Link] Biopsy (Indications)
Steroid Resistant Nephrotic Syndrome
Frequent Relapses
Steroids Toxicity
Age at onset < 1or >8 years
Hypertension
Gross Hematuria
Low plasma C3
Renal insufficiency
Secondary Nephrotic Syndrome
Important Definitions
Remission
Urine trace or negative for protein for 3 consecutive days
Steroid resistant
If the child continues to have Proteinuria (2 plus or more) on daily
steroid therapy after 8 wks.
Relapse
Proteinuria 3-4 + with Oedema.
Steroid dependent
Relapse while on alternate day therapy or within 28 days of stopping
Steroid therapy.
Frequent relapser
Four or more relapses in 12 months.
Management
Supportive
1) Hospitalization (Indications)
Infection
Marked Edema
2) Diet
A balanced diet adequate in proteins and calories
Salt and fluid restriction when edema
3) Infection
Antibiotics
4) Diuretics
Indications:
Pleural Effusion
Ascites
Severe Genital Edema
Treatment (Edema)
Sodium restriction
Fluid restriction
Diuretics
25 % Salt poor human albumin infusion
Specific
1) Steroids( Oral Prednisolone)
60 mg/m2/day for 4 weeks
40 mg/m2/AD for 4 weeks
Withdrawal
Gradual over next 2-3 months
Dose decreased every 2 weeks by 15 mg/m2
2) Treatment of steroid dependant and Frequent
relapsers
6-12 months AD single dose
Dose School going 0.5 mg/kg AD
Preschool 1 mg/kg/AD
3) Alternative Therapy
Indications
A) Relapse on Prednisolone dosage > 1 mg/kg AD
OR
B) Relapse on Prednisolone dosage > 0.5 mg/kg AD
Plus
Steroid Toxicity or Severe Relapse
Drugs
Cyclophosphamide
Levamisole
Cyclosporin
Chlorambucil
4) Steroid Resistant Nephrotic Syndrome
Methylprednisolone
Cyclophosphamide
ACE inhibitors
Angiotensin II Blockers
Complications
1)Infections
Spontaneous bacterial peritonitis
Pneumonia
UTI
Sepsis
Cellulites
2)Arterial and Venous Thrombosis
3) Others
Steroids and other drugs adverse effects
PROGNOSIS
1) Responders (78%)
92 % Minimal Change
8 % Others
Non responders (22 %)
25 % Minimal change
25%Focal Sclerosis
25 % Mesangial Proliferation
25 % Others
2) Response Time
10 % by the end of 1st Week
70 %by the end of 2nd Week
85 %by the end of 3rd Week
92 %by the end of 4th Week
3) Steroid responsiveness
90 % Minimal change disease
50 % Mesangial proliferation
20 % Focal Sclerosis
4) Poor prognostic factors are
Hematuria
Hypertension
Hypocomplementemia
Focal segmental sclerosis
Steroid resistance
Thank You
