Nephrotic Syndrome - Short Note (6 Marks)

Definition

• Massive proteinuria - urinary protein loss ≥3.5 g/day in adults (in children: >50 mg/kg/24 h)
• Hypoalbuminemia - serum albumin <3 g/dL
• Generalised edema
• Hyperlipidemia and lipiduria

Pathophysiology

1. Proteinuria - damaged GBM fails to restrict plasma proteins
2. Hypoalbuminemia - urinary albumin loss exceeds hepatic synthetic capacity; renal catabolism of filtered albumin also contributes
3. Edema - reduced intravascular oncotic pressure increases fluid flux into interstitium ("underfill" mechanism); compensatory aldosterone secretion, sympathetic activation, and reduced ANP secretion cause Na+/water retention ("overfill" mechanism)
4. Hyperlipidemia - liver compensatorily increases lipoprotein synthesis; impaired peripheral lipid catabolism. Results in raised LDL, VLDL, cholesterol, triglycerides, and lipoprotein(a)
5. Lipiduria - lipoproteins filtered through damaged glomeruli appear as oval fat bodies or fatty casts in urine

Causes

Clinical Features

• Edema: soft, pitting, characteristically periorbital (especially morning), progresses to dependent edema, and if severe - ascites and pleural effusions
• Heavy proteinuria - foamy urine
• Features of the underlying cause (e.g., diabetic retinopathy in DM)
• Blood pressure may be normal or elevated

Complications

1. Infections - especially Staphylococcus and Pneumococcus, due to urinary loss of immunoglobulins
2. Thromboembolism - loss of anticoagulants (antithrombin III, protein C and S) in urine → hypercoagulable state → renal vein thrombosis, DVT, pulmonary embolism (particularly in membranous nephropathy)
3. Dyslipidemia & accelerated atherosclerosis
4. Protein malnutrition - loss of binding proteins (thyroid-binding globulin, transferrin, vitamin D-binding protein) leads to thyroid, iron, and vitamin D deficiency
5. Progressive CKD - proteinuria itself is nephrotoxic; continued glomerular loss leads to declining GFR

Management

• Diuretics (loop diuretics) for edema - avoid overly aggressive diuresis causing intravascular volume depletion
• ACE inhibitors or ARBs - reduce proteinuria, combat dyslipidemia, edema, coagulopathy, and slow progression of CKD
• SGLT2 inhibitors - lower urinary protein excretion and preserve renal function (per Harrison's 22E, 2025)
• Statins - treat hypercholesterolemia, reduce cardiovascular risk
• Anticoagulation - for thromboembolic complications

• Minimal Change Disease: Steroids (prednisone) - high remission rate
• Membranous Nephropathy: Steroids ± cyclophosphamide/calcineurin inhibitors; rituximab (anti-CD20)
• FSGS: Steroids; calcineurin inhibitors for steroid-resistant cases
• Secondary causes: treat the underlying disease