Nephrotic Syndrome

Clinical assessment

Suspect based on presentation with significant oedema and frothy urine. Assess for underlying causes/risk factors. Differentiate from other causes of generalized oedema (heart failure, liver cirrhosis, malnutrition, lymphatic obstruction).

Investigations

• Urinalysis: Heavy proteinuria (3+ or 4+ on dipstick). Microscopy may show oval fat bodies, fatty casts.
• Quantification of Proteinuria: 24-hour urine protein collection (>3.5 g/day) OR Spot urine Protein-to-Creatinine Ratio (PCR) or Albumin-to-Creatinine Ratio (ACR) - PCR >200-300 mg/mmol or ACR >220 mg/mmol strongly suggests nephrotic range.
• Blood tests:
• - Serum Albumin: Low (<30 g/L, often <25 g/L).
• - Serum Creatinine/Urea/eGFR: Assess renal function (may be normal or impaired).
• - Lipid Profile: Elevated cholesterol (total and LDL), elevated triglycerides.
• - Serology for secondary causes: HBsAg, Anti-HCV, HIV test, ANA, Complement levels (C3/C4).
• - Serum Protein Electrophoresis (consider if myeloma suspected).
• Kidney Ultrasound: Rule out other renal pathology.
• Kidney Biopsy: Often required in adults to determine the specific underlying glomerular disease and guide treatment. May be deferred in children with typical features suggesting Minimal Change Disease who respond to steroids.

Diagnostic criteria

Presence of nephrotic-range proteinuria (>3.5g/day or equivalent ratio) PLUS hypoalbuminemia (<30g/L), usually accompanied by oedema and hyperlipidemia.

Non-pharmacological management

• Dietary Management:
• - Sodium Restriction (<2g/day) to help manage oedema.
• - Fluid Restriction may be needed if hyponatremic or severe oedema.
• - Adequate protein intake (excessive restriction not usually recommended unless advanced CKD).
• - Management of hyperlipidemia (diet, statins).
• Monitor daily weight, fluid balance (I/O chart).
• Compression stockings for peripheral oedema.
• Preventative measures for complications (see below).

Pharmacological treatment

• Treat the Underlying Cause (if secondary nephrotic syndrome).
• Management of Oedema:
• - Loop Diuretics: Furosemide PO/IV. Often requires high doses and sometimes combination with thiazide diuretic (e.g., Metolazone) due to diuretic resistance. Monitor electrolytes closely.
• - IV Albumin infusion followed by IV Furosemide: May be used in severe refractory oedema/hypovolemia (specialist).
• Reduce Proteinuria:
• - ACE Inhibitors (ACEi) or Angiotensin Receptor Blockers (ARBs): Reduce intraglomerular pressure and proteinuria. Titrate dose as tolerated, monitor BP, K+, Cr.
• Manage Hyperlipidemia:
• - Statins (e.g., Atorvastatin, Simvastatin).
• Prevent Thrombosis:
• - Anticoagulation (e.g., Warfarin, LMWH, DOACs): Consider prophylactic or therapeutic anticoagulation if high risk of thromboembolism (e.g., very low albumin <20-25g/L, additional risk factors). Decision requires careful risk-benefit assessment (specialist).
• Specific Therapy for Primary Glomerular Disease (Requires biopsy results/specialist management):
• - Minimal Change Disease: Corticosteroids (Prednisolone) 1-2mg/kg/day (max 60-80mg) is first-line. High response rate. Gradual taper after remission.
• - FSGS / Membranous / MPGN / others: Treatment often involves corticosteroids +/- other immunosuppressants (e.g., Cyclophosphamide, Ciclosporin, Tacrolimus, Rituximab) based on specific diagnosis and severity.

Monitoring

Monitor weight, oedema, BP, fluid balance. Monitor urine protein excretion (dipstick, PCR/ACR). Monitor serum albumin, creatinine, electrolytes, lipids. Monitor for complications (infection, thrombosis). Monitor side effects of medications (steroids, immunosuppressants).