Nephrotic Syndrome

Pathophysiology

• Glomerular injury leading to massive proteinuria (>3.5 g/day)

• Hypoalbuminaemia due to urinary loss of protein → oedema

• Hyperlipidaemia due to compensatory hepatic lipid synthesis

• Hypercoagulability from loss of antithrombin III, protein C, and protein S in urine

Causes

• Diabetes, SLE, Amyloidosis: Account for ~⅓ of cases (secondary causes)

• Primary Glomerular Diseases:

  • Minimal Change Disease (MCD): Most common in children; typically steroid-responsive

  • Membranous Nephropathy: Most common in adults; can be linked to malignancy, infections, autoimmune

  • Focal Segmental Glomerulosclerosis (FSGS): May be idiopathic or secondary (obesity, HIV)

  • IgA Nephropathy: More commonly nephritic, but can have nephrotic-range proteinuria

  • HIV-Associated nephropathy

Clinical Presentation

• Severe Oedema: Periorbital (in mornings), lower limb, anasarca

• Foamy Urine: Due to proteinuria

• Dyspnoea: Secondary to fluid overload (pulmonary oedema, pleural effusions)

• Features of underlying disease: e.g. rash/arthralgia (SLE), neuropathy (amyloidosis/diabetes), hepatosplenomegaly (amyloidosis)

Key Lab Features

• Proteinuria >3.5 g/day (ACR >300 mg/mmol)

• Hypoalbuminaemia <25 g/L

• Hyperlipidaemia (high LDL, triglycerides)

• Hypercoagulability → ↑ risk of DVT/PE

• ↑ Infection Risk: Loss of immunoglobulins (IgG) in urine

Investigations

Initial Workup

• UEC: Assess renal function

• Urine MCS: Exclude infection; check for casts

• Urine PCR/ACR or 24-hour protein: Quantify proteinuria

• LFTs: Assess hypoalbuminaemia, exclude liver disease

• Lipid Profile: Evaluate hyperlipidaemia

• Coagulation Studies: Risk of thrombosis

Identify Underlying Cause

• Autoimmune: ANA, C3/C4 (SLE)

• Diabetes: HbA1c, fasting glucose

• Paraproteins: Serum/urine electrophoresis for amyloidosis or multiple myeloma

• Hepatitis B/C, HIV serologies

• Renal Ultrasound: Rule out structural issues, detect possible renal vein thrombosis

• Renal Biopsy: Definitive diagnosis unless a clear secondary cause (e.g. longstanding diabetes with typical changes)

Management

General Measures

• ACE Inhibitors / ARBs: Reduce proteinuria, target BP <130/80 mmHg

• Salt & Fluid Restriction if oedema is significant

• Daily Weights: Track fluid overload

• Diuretics (loop ± spironolactone) for volume management

• Statins if persistent dyslipidaemia or high cardiovascular risk

• Aspirin for atherosclerotic risk if indicated (e.g., diabetes, prior MI/stroke)

Immunosuppression (if primary GN or immune-mediated):

• Corticosteroids: First-line in minimal change, can be used in FSGS, SLE nephritis

• Cyclophosphamide / Calcineurin Inhibitors (cyclosporine, tacrolimus) for steroid-resistant or relapsing cases

• Mycophenolate Mofetil: Alternative in some glomerulopathies

Infection & Thrombosis Prevention

• Vaccinations: Influenza, pneumococcal, hepatitis B

• Prophylactic Antibiotics if recurrent infections or significant immunosuppression

• Anticoagulation: Consider if albumin <20 g/L or history of DVT/PE

Notes

• Minimal Change Disease: Common in children, highly steroid-responsive

• Membranous Nephropathy: Most frequent adult cause, often associated with malignancies/infections/autoimmune

• ACE/ARB therapy is essential to slow progression and reduce proteinuria

• Patients have high risk of infections & thrombosis → monitor carefully

• Renal Biopsy needed for definitive diagnosis unless the cause is clearly secondary (longstanding T2DM with typical features)