Nephrotic Syndrome: Symptoms, Pathophysiology, and Management

Nephrotic syndrome is a clinical constellation defined by:

1. Heavy proteinuria: >3.5 g/day (adults) or >40 mg/m²/hr (children) or UPCR >2.
2. Hypoalbuminemia: Serum albumin <3.0 g/dL.
3. Edema: Periorbital (morning), peripheral (dependent), ascites, pleural effusions.
4. Hyperlipidemia: ↑ LDL, VLDL, triglycerides; ↓ HDL.

Lipiduria (oval fat bodies) and hypogammaglobulinemia (urinary IgG loss) may also occur.

Primary (Renal-Limited) Causes

• Minimal change disease (MCD): #1 in children; selective proteinuria; steroid-responsive.
• Focal segmental glomerulosclerosis (FSGS): Leading cause in adults; steroid-resistant; recurrence post-transplant.
• Membranous nephropathy (MN): #1 in adults; anti-PLA2R antibodies (70%); variable course.
• Membranoproliferative GN (MPGN): Complement-mediated (C3G) or immune-complex.

Secondary Causes

• Diabetic nephropathy (most common overall).
• Lupus nephritis (Class V).
• Amyloidosis (AL).
• Drugs: NSAIDs, gold, penicillamine, interferon.
• Infections: Hepatitis B/C, syphilis, malaria.
• Malignancy: Solid tumors, lymphoma.

Management

Supportive

• Edema: Loop diuretics (furosemide) ± thiazide; albumin infusion if refractory + diuretic.
• Hyperlipidemia: Statins (CV risk reduction); treat if persistent.
• Thromboprophylaxis: Anticoagulate if serum albumin <2.0 g/dL + additional risk factors (immobility, surgery, history VTE).
• Infection prophylaxis: Pneumococcal vaccine; consider penicillin if severe/relapsing.

Disease-Specific

• MCD: Prednisone 60 mg/m²/day × 4–6 wks → taper. 90% remission. Relapse common → steroid-sparing (CNI, MMF, rituximab).
• FSGS: High-dose steroids × 16 wks; if resistant → calcineurin inhibitors (tacrolimus), rituximab.
• MN: Risk-stratified: Low-risk (monitor); high-risk (anti-PLA2R high, persistent nephrotic) → rituximab ± CNI.
• Secondary: Treat underlying (diabetes, lupus, infection, stop drug).

Monitoring

• Urine protein/creatinine ratio, albumin, lipids, renal function, BP, weight.
• Relapse = proteinuria recurrence after remission.

Early nephrology referral improves outcomes. Remission (complete/partial) predicts long-term renal survival.