Nephrotic Syndrome

Glomerular disorder characterized by massive proteinuria (>3.5 g/24 hours in adults or >40 mg/m²/hour in children), leading to hypoalbuminemia, generalized edema, hyperlipidemia, and lipiduria

Aetiology

Primary (Idiopathic) Glomerular Diseases

1. Minimal Change Disease (MCD)
• Most common cause in children
• Often associated with atopy, infection, or vaccination

2. Focal Segmental Glomerulosclerosis (FSGS)
• Most common cause in adults
• Can be primary or secondary (HIV, obesity, sickle cell disease)

3. Membranous Nephropathy
• Common in adults
• May be idiopathic (anti-PLA2R antibodies) or secondary

4. Membranoproliferative GN (rarely nephrotic-predominant)

Secondary Causes

• Diabetes mellitus (diabetic nephropathy)

• Systemic lupus erythematosus

• Amyloidosis

• Infections (HIV, hepatitis B and C)

• Drugs (NSAIDs, gold)

• Malignancies (solid tumors, lymphoma)

Pathophysiology

• Podocyte injury → effacement of foot processes

• Loss of size and charge selectivity of GBM

• Massive leakage of plasma proteins, especially albumin

• Hypoalbuminemia → decreased plasma oncotic pressure

• Compensatory hepatic synthesis of lipoproteins → hyperlipidemia

• Sodium and water retention → generalized edema

Clinical presentation

Edema (Cardinal Feature)

• Generalized (anasarca)

• Periorbital edema (morning)

• Peripheral edema

• Ascites and pleural effusion in severe cases

Urinary Abnormalities

• Frothy or foamy urine

• Oliguria (in advanced disease)

• Lipiduria (fatty casts, oval fat bodies)

Systemic Manifestations

• Fatigue

• Weight gain

• Susceptibility to infections

• Thromboembolic events (renal vein thrombosis, DVT)

Investigations

Urinalysis

• Proteinuria >3.5 g/day

• Fatty casts

• Oval fat bodies (Maltese cross under polarized light)

Blood Tests

• Hypoalbuminemia

• Hyperlipidemia

• Possible azotemia in advanced disease

• Reduced immunoglobulins

Serologic and Etiologic Workup

• ANA, anti-dsDNA

• Hepatitis B and C serology

• HIV testing

• Anti-PLA2R antibodies (membranous nephropathy)

Renal Biopsy

• Indicated in most adults

• Often not required in children with suspected MCD

Management

• Salt restriction

• Fluid restriction (if significant edema)

• Corticosteroids
• Prednisone 2mg/kg/day

• Diuretics (loop ± thiazide)
• Furosemide 1-3mg/kg/day

• ACE inhibitors or ARBs to reduce proteinuria

• Statins for hyperlipidemia

• Anticoagulation (selected high-risk patients)