Nephrotic syndrome

Nephrotic syndrome is a clinical disorder characterized by massive protein loss in urine resulting from increased glomerular permeability, leading to generalized oedema, hypoalbuminaemia, and hyperlipidaemia.

It represents a manifestation of underlying glomerular disease rather than a single disease entity. Nephrotic syndrome may occur in both children and adults and carries significant risks including infection, thromboembolism, malnutrition, and progressive kidney failure.

The condition results from structural or functional damage to the glomerular filtration barrier, allowing excessive plasma proteins—especially albumin—to leak into urine.

Key clinical triad

• Oedema

• Hypoalbuminaemia

• Hyperlipidaemia

Important Note:Accurate etiological diagnosis generally requires a renal biopsy, particularly in adults.

Etiology and Pathophysiology

Damage to podocytes and glomerular basement membrane causes:

1. Increased permeability to plasma proteins

2. Heavy proteinuria (>3.5 g/day)

3. Reduced plasma oncotic pressure

4. Fluid shift into interstitial space → oedema

5. Compensatory hepatic lipid synthesis → hyperlipidaemia

Primary (Idiopathic) Glomerular Causes

Secondary Causes

• Diabetes mellitus

• Systemic lupus erythematosus

• Amyloidosis

• Infections (Hepatitis B, Hepatitis C, HIV)

• Malignancy

• Drugs (NSAIDs, gold, penicillamine)

• Obesity-related kidney disease

Risk Factors

• Diabetes mellitus

• Autoimmune diseases

• Chronic infections

• Genetic predisposition

• Exposure to nephrotoxic drugs

• Malignancies

• Obesity

• Chronic inflammatory disorders

Signs and Symptoms

Cardinal Features

• Generalized oedema (anasarca)

• Periorbital swelling (early sign)

• Lower limb oedema

• Ascites

• Pleural effusion

Urinary Features

• Frothy or foamy urine

• Reduced urine output (occasionally)

Systemic Manifestations

• Fatigue

• Weight gain due to fluid retention

• Loss of appetite

• Susceptibility to infections

Complication-Related Symptoms

• Deep vein thrombosis

• Pulmonary embolism

• Recurrent infections

• Hypertension (variable)

Diagnostic Criteria

Diagnosis is based on clinical and laboratory findings:

• Oedema

• Heavy proteinuria (>3.5 g/24 hours or urine protein–creatinine ratio equivalent)

• Hypoalbuminaemia (<30 g/L)

• Hyperlipidaemia

Note:Definitive diagnosis of underlying glomerular disease requires renal biopsy, especially in adults or atypical presentations.

Investigations

Urine Tests

• Urinalysis (proteinuria)

• Urine protein quantification

• Urine protein–creatinine ratio

• Microscopy for casts

Blood Tests

• Serum albumin

• Lipid profile

• Renal function tests (urea, creatinine)

• Electrolytes

• Full blood count

Etiological Screening

• Blood glucose / HbA1c

• ANA, anti-dsDNA (autoimmune disease)

• Complement levels

• Hepatitis B & C screening

• HIV testing

• Serum protein electrophoresis

Imaging

• Renal ultrasound (kidney size and structure)

Definitive Investigation

• Renal biopsy (histological classification and treatment guidance)

Management

Management goals include:

• Control oedema

• Reduce proteinuria

• Prevent complications

• Treat underlying cause

• Preserve kidney function

Treatment is individualized and guided by nephrology specialists.

Pharmacological Management

Management depends on biopsy-confirmed diagnosis.

Immunosuppressive Therapy

(Under nephrologist supervision)

May include:

• Prednisolone

• Mycophenolate mofetil

• Cyclophosphamide

• Calcineurin inhibitors (e.g., cyclosporine, tacrolimus)

• Rituximab (selected cases)

Supportive Medical Therapy

1. Renin–Angiotensin System Blockade

• ACE inhibitors or ARBs→ Reduce proteinuria and slow disease progression

2. Diuretics

• Furosemide ± spironolactone→ Control oedema

3. Lipid-lowering Therapy

• Statins for persistent hyperlipidaemia

4. Anticoagulation

Consider in:

• Severe hypoalbuminaemia

• High thrombotic risk

5. Infection Management

• Prompt antibiotic treatment when indicated

• Vaccination where appropriate

Non-Pharmacological Management

• Adequate caloric intake

• Protein intake approximately 1 g/kg/day

• No added salt diet to reduce fluid overload

• Fluid restriction in severe oedema

• Daily weight monitoring

• Blood pressure control

• Avoid nephrotoxic medications (e.g., NSAIDs)

Complications

• Acute kidney injury

• Chronic kidney disease

• Thromboembolism

• Severe infections

• Malnutrition

• Hypovolaemia

• Cardiovascular disease

Prevention

Although primary prevention is limited, progression can be reduced through:

• Early treatment of diabetes and hypertension

• Infection prevention

• Avoidance of nephrotoxic drugs

• Regular renal monitoring in high-risk patients

• Early specialist referral

• Adherence to prescribed therapy

Patient Education

Patients should be educated to:

• Monitor swelling and daily body weight

• Reduce dietary salt intake

• Take medications consistently

• Seek care for fever or sudden limb swelling

• Avoid over-the-counter nephrotoxic drugs

• Attend regular nephrology follow-up

Indications for Nephrology Referral

• Suspected nephrotic syndrome

• Persistent heavy proteinuria

• Declining renal function

• Resistant oedema

• Uncertain diagnosis

• Requirement for renal biopsy or immunosuppressive therapy

Prognosis

Outcome depends on:

• Underlying histological type

• Response to therapy

• Degree of renal impairment

• Presence of complications

Minimal Change Disease often responds well to therapy, whereas FSGS and secondary causes may progress to chronic kidney disease.