Ref: Nelson and ISPN guidelines.

1. NEPHROTIC SYNDROME
(NS)
DR.M.SUCINDAR
ASST. PROF
DEPT. OF PEDIATRICS
RMMCH

2. CONTENTS
• DEFINITION
• ETIOLOGY
• PATHOGENESIS
• CLINICAL FEATURES
• INVESTIGATIONS
• TREATMENT
• COMPLICATIONS

3. DEFINITION
• Nephrotic syndrome is the clinical manifestation
of glomerular diseases associated with heavy
(nephrotic-range) proteinuria.
• Nephrotic range proteinuria (Urine protein >3.5
g/24 hr or 40 mg/m2/hr or spot urine protein :
creatinine ratio >2 or early morning urine protein
3+ / 4+ on dipstick)
• Hypoalbuminemia (≤2.5 g/dL),
• Edema, and
• Hyperlipidemia (cholesterol >200 mg/dL).

4. ETIOLOGY
• Primary or Idiopathic
• Secondary
• Hereditary

5. PRIMARY OR IDIOPATHIC
CAUSES
• Minimal change disease (Most common)
• Focal segmental glomerulosclerosis
• Membranous nephropathy
• Membranoproliferative glomerulonephritis
• Membranous nephropathy

6. SECONDARY CAUSES
• Infections
• Endocarditis
• Hepatitis B, C
• HIV-1
• Infectious mononucleosis
• Malaria
• Syphilis (congenital and
secondary)
• Toxoplasmosis
• Schistosomiasis
• Filariasis
• Drugs
• Captopril
• Penicillamine
• Gold
• Nonsteroidal antiinflammatory
drugs
• Pamidronate
• Interferon
• Mercury
• Heroin
• Lithium
• Immunologic or Allergic
Disorders
• Vasculitis syndromes
• Bee sting
• Food allergens
• Serum sickness
• Associated With Malignant
Disease
• Lymphoma
• Leukemia
• Solid tumors

7. HEREDITARY CAUSES
• Nephrotic Syndrome (Typical)
• Finnish-type congenital nephrotic syndrome (absence of nephrin)
• Diffuse mesangial sclerosis (mutations in laminin β2 chain)
• Denys-Drash syndrome (mutations in WT1 transcription factor)
• Proteinuria With or Without Nephrotic Syndrome
• Nail-patella syndrome (mutation in LMX1B transcription factor)
• Alport syndrome (mutation in collagen biosynthesis genes)

8. PATHOGENESIS
• Glomerular capillary wall –
Podocytes and Slit diaphragm.
• Immune and nonimmune insults to
the podocyte that lead to foot process
effacement of the podocyte, a decrease
in number of functional podocytes,
and altered slit diaphragm integrity.
• Important component proteins of the
slit diaphragm include nephrin,
podocin, CD2AP, and α-actinin 4.
• Podocyte injury or genetic mutations of
genes producing podocyte proteins
may cause nephrotic-range
proteinuria.
• Increased permeability of the
glomerular capillary wall, which
leads to massive proteinuria and
hypoalbuminemia.

9. CLINICAL FEATURES
• Idiopathic NS - Most common (90%)
• MCNS (85%)
• 2 to 6 years of age
• More common in boys.
• Edema
• Hyperlipidemia
• Increased susceptibility to infections
• Hypercoagulability

10. EDEMA
• Underfill hypothesis
• Hypoalbumenia
• ↓ oncotic pressure
• Leakage of plasma into
interstitium.
• Overfill hypothesis
• Epithelial sodium
channel in distal
tubule
• Primary sodium
retention
• Volume expansion
• Leakage of excess fluid
into interstitium.

11. HYPERLIPIDEMIA
• Increased synthesis of lipids:
Hypoalbumenia -> hepatic synthesis of lipoproteins
• Decreased catabolism of lipids:
Urinary loss of Lipase
• Increase in cholesterol, triglycerides, low-density
lipoprotein, and very-low-density lipoproteins.

12. Increased susceptibility to infections
• Urinary losses of immunoglobulin, complement
factors (predominantly C3 and C5).
• Increased susceptibility to infections with
encapsulated bacteria (pneumococcus).
• Cellulitis, spontaneous bacterial peritonitis, and
bacteremia.

13. HYPERCOAGULABILITY
• Hemoconcentration and intravascular volume
depletion, increased platelet number and
aggregability, and changes in coagulation factor
levels.
• Increase in hepatic production of fibrinogen along
with urinary losses of antithrombotic factors such
as antithrombin III and protein S.

14. INVESTIGATIONS
• Urinalysis reveals 3+ or 4+ proteinuria, and
microscopic hematuria is present in 20% of
children.
• A spot urine protein : creatinine ratio >2.0.
• Serum albumin level is <2.5 g/dl.
• Serum cholesterol and triglyceride levels - elevated.
• Serum creatinine value - usually normal.
• Serum complement levels - normal.
• Renal biopsy – not routinely indicated.

15. MCNS
• Light microscopy: Normal
• Immunofluorescence: Negative
• Electron microscopy: Foot process fusion

16. TREATMENT
• Corticosteroids – mainstay of therapy.
• INITIAL EPISODE:
• Oral Prednisolone:
at a dose of 2 mg/kg per day (maximum 60
mg in single or divided doses) for 6 weeks, followed
by 1.5 mg/kg (maximum 40 mg) as a single
morning dose on alternate days for the next 6
weeks; therapy is then discontinued.

17. Supportive Therapy
• Diet:
• High protein diet (2 – 2.5 g/kg/day)
• Low fat diet (<30% of calories)
• Sodium restriction (1 – 2 g/day)
• Edema management:
• Fluid restriction
• Loop diuretics (furosemide) (1–3 mg/kg/day) ±
Spironolactone (2–4 mg/kg/day)
• Hydrochlorothiazide (1-2 mg/kg/day)
• Refractory -> IV Albumin 20% (0.5–1 g/kg) as slow
infusion followed by IV Furosemide (1–2 mg/kg).

18. • Dyslipidemia:
• Low fat diet.
• Infections:
• 3rd
generation Cephalosporin.
• Thromboembolism:
• Heparin (LMW) and Warfarin.

19. • Response: The attainment of remission within the
initial 4 wk of corticosteroid therapy.
• Remission: Urine albumin nil or trace (or
proteinuria <4 mg/m2/h) for 3 consecutive early
morning specimens.
• Relapse: Urine albumin 3+ or 4+ (or proteinuria
>40 mg/m2/h) for 3 consecutive early morning
specimens, having been in remission previously.
• Frequent relapses: Two or more relapses in initial
six months or more than three relapses in any
twelve months.

20. • Steroid dependence: Two consecutive relapses
when on alternate day steroids or within 14 days of
its discontinuation.
• Steroid resistance: Absence of remission despite
therapy with daily prednisolone at a dose of 2
mg/kg per day for 4 weeks.

21. Relapse Treatment
• Prednisolone is administered at a dose of 2
mg/kg/day (single or divided doses) until urine
protein is trace or nil for three consecutive days.
• Subsequently, prednisolone is given in a single
morning dose of 1.5 mg/kg on alternate days for 4
weeks, and then discontinued.
• The usual duration of treatment for a relapse is
thus 5-6 weeks.

22. Frequent relapse or Steroid dependence
or Steroid resistant
• Alternate day steroid therapy (9 to 18 months)
• Steroid toxicity:
• Cyclophosphamide or
• Calcineurin inhibitors (Cyclosporin or Tacrolimus)
or
• Levamisole or
• Mycophenolate mofetil or
• Rituximab
• +
• Adjuncts (ACE inhibitors or AT II receptor
antagonist).

23. • Immunization:
• Pneumococcal vaccination
• Influenza vaccination

24. COMPLICATIONS
• Infections: Peritonitis,
cellulitis, pneumonia,
fungal infections and
varicella.
• Thrombosis: Renal vein
thrombosis.
• Hypertension
• Hypovolemic shock
• Steroid toxicity:
• Cushingoid features,
• Increased appetite,
• Impaired growth,
• Behavioral changes,
• Risk of infections,
• Salt and water
retention,
• Hypertension and
• Bone demineralization.

25. THANK YOU