Nephrotic Syndrome

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management

Definition

Nephrotic syndrome is a clinical condition characterised by:

  • Heavy proteinuria (>3.5g/24 hours).
  • Hypoalbuminaemia (<30 g/L).
  • Oedema.
  • Hyperlipidaemia.

Aetiology

Primary Causes:

  • Minimal Change Disease (MCD): most common cause in children, responds well to steroids.
  • Focal Segmental Glomerulosclerosis (FSGS): common in adults, associated with progressive renal decline.
  • Membranous Nephropathy: common in adults, often associated with autoimmune diseases.

Secondary Causes:

  • Diabetes Mellitus (diabetic nephropathy).
  • Lupus Nephritis (systemic lupus erythematosus).
  • Hepatitis B and C.
  • HIV-associated nephropathy.
  • Medications (NSAIDs, gold therapy, penicillamine).

Pathophysiology

  • Glomerular damage leads to increased permeability of the glomerular basement membrane.
  • Excessive protein loss in urine (proteinuria) results in hypoalbuminaemia.
  • Reduced oncotic pressure leads to fluid leakage into tissues, causing oedema.
  • The liver compensates by increasing lipoprotein synthesis, leading to hyperlipidaemia.

Risk Factors

  • Diabetes mellitus.
  • Autoimmune diseases (e.g., lupus, vasculitis).
  • Chronic infections (HIV, hepatitis B/C).
  • Prolonged use of nephrotoxic drugs (NSAIDs, antibiotics).
  • Genetic predisposition (familial FSGS).

Signs and Symptoms

  • Generalised oedema: commonly periorbital, lower limb, and sacral oedema.
  • Frothy urine: due to excessive protein excretion.
  • Fatigue and lethargy: due to protein loss.
  • Infections: increased susceptibility due to immunoglobulin loss.
  • Venous thromboembolism (VTE): increased clotting risk due to loss of antithrombin III.
  • Hyperlipidaemia: xanthelasma may be present in severe cases.

Investigations

  • Urine dipstick: proteinuria (3+ or 4+).
  • Urinary Protein:Creatinine Ratio (PCR): confirms nephrotic-range proteinuria.
  • Serum Albumin: typically <30 g/L.
  • Renal Function Tests (U&Es): assess kidney function.
  • Lipid Profile: elevated cholesterol and triglycerides.
  • Autoimmune Screen: ANA, ANCA, anti-dsDNA (if secondary cause suspected).
  • Renal Biopsy: required for definitive diagnosis unless MCD is suspected.

Management

1. General Measures:

  • Salt and fluid restriction: helps reduce oedema.
  • High-protein diet: to compensate for protein loss.
  • Blood pressure control: target <130/80 mmHg (ACE inhibitors or ARBs).

2. Pharmacological Management:

First-Line Treatment:
  • corticosteroids (e.g., Prednisolone 1 mg/kg/day): First-line for Minimal Change Disease.
Adjunctive Therapies:
  • Diuretics (e.g., Furosemide): used for oedema control.
  • ACE inhibitors or ARBs: reduce proteinuria and protect kidney function.
  • Statins: for hyperlipidaemia.
  • Anticoagulation: if high risk of VTE.

3. Management of Refractory or Severe Cases:

  • Immunosuppressants: Ciclosporin, Cyclophosphamide, or Rituximab in steroid-resistant cases.
  • Plasma exchange: in rapidly progressive nephrotic syndromes.

4. Monitoring and Follow-Up:

  • Regular urinalysis to monitor proteinuria.
  • Renal function assessment every 3–6 months.
  • Long-term surveillance for thromboembolic events.
RenalmypanotesNephrotic Syndrome