Define Nephrotic Syndrome. Describe its aetiology, pathophysiology, clinical features and investigations.

Definition

Nephrotic syndrome is a clinical state resulting from heavy urinary protein loss, defined by a tetrad:

• Massive proteinuria — > 40 mg/m²/hour, or a urine protein:creatinine ratio > 2 mg/mg, or 3+/4+ on dipstick.
• Hypoalbuminaemia — serum albumin < 2.5 g/dL.
• Oedema.
• Hyperlipidaemia.

Etiology

• Idiopathic (~90%) — Minimal Change Disease (MCD) is by far the commonest (~85% in children) and is usually steroid-responsive; also focal segmental glomerulosclerosis (FSGS) and membranoproliferative GN.
• Congenital nephrotic syndrome (first 3 months; e.g. Finnish type).
• Secondary — Henoch-Schönlein purpura, SLE, infections (hepatitis B, malaria), drugs.

Pathophysiology

Podocyte injury → increased glomerular capillary permeability → Massive proteinuria → Hypoalbuminaemia → fall in plasma oncotic pressure → Fluid shifts to interstitium → oedema → Liver increases lipoprotein synthesis → hyperlipidaemia

Clinical Features

• Oedema — insidious; typically starts as periorbital puffiness (worse in the morning), then becomes generalised (anasarca) with ascites and pleural effusions.
• Frothy urine and decreased urine output; weight gain.
• Blood pressure is usually normal in MCD (hypertension/haematuria suggest a non-MCD cause).
• The child is usually 2–6 years old (MCD age group).

Investigations

• Urine — 3+/4+ protein; spot protein:creatinine ratio; microscopy (hyaline casts; RBCs suggest nephritic overlap).
• Blood — low albumin, high cholesterol; renal function; C3 (normal in MCD).
• Renal biopsy — not routine; reserved for atypical features (age < 1 or > 12 yr, gross haematuria, hypertension, low C3, renal failure) or steroid resistance.

Definitions (important for Management)

• Remission — urine protein nil/trace for 3 consecutive days.
• Relapse — 3+/4+ proteinuria for 3 consecutive days.
• Frequent relapse — ≥ 2 relapses in 6 months (or ≥ 4 in a year); steroid-dependent — relapse on tapering or within 2 weeks of stopping steroids.
• Steroid-resistant — no remission despite 4–6 weeks of daily steroids.

Management

• Corticosteroids — prednisolone 2 mg/kg/day (60 mg/m²/day) for 6 weeks, then 1.5 mg/kg (40 mg/m²) on alternate days for 6 weeks, then taper (first episode).
• Supportive — salt restriction, diuretics for severe oedema, and IV albumin for refractory oedema/hypovolaemia.
• Infection prophylaxis — penicillin and pneumococcal vaccination (encapsulated-organism risk).
• Relapses/complex disease — steroid-sparing agents (levamisole, cyclophosphamide, calcineurin inhibitors, mycophenolate) for frequent-relapsing/steroid-dependent/steroid-resistant disease.

Complications

• Infections — spontaneous bacterial peritonitis (pneumococcal), cellulitis, pneumonia (loss of immunoglobulins).
• Thromboembolism — a hypercoagulable state (loss of antithrombin III).
• Hypovolaemia and acute kidney injury; hyperlipidaemia; and steroid toxicity.

Epidemiology

• Incidence ~2–7 per 100,000 children; commoner in boys.
• Minimal change disease peaks between 2 and 6 years of age.

Nephrotic VS Nephritic Syndrome

Monitoring

• Home urine dipstick diary to detect relapse; daily weight during acute phase.
• Blood pressure, growth and steroid side-effects (cushingoid features, cataract, bone health) at each visit.

Prognosis

• Minimal change disease has an excellent long-term prognosis — most children are steroid-responsive and, although relapses are common, the majority 'outgrow' the tendency by adolescence with preserved kidney function.
• Steroid-resistant disease (often FSGS) carries a higher risk of progression to chronic kidney disease.

Pathology

• In minimal change disease the glomeruli look normal on light microscopy; the only abnormality is effacement (fusion) of the podocyte foot processes on electron microscopy — hence the name.
• This explains its selective proteinuria and steroid responsiveness.