From the Guidelines
The workup for nephrotic syndrome should include a comprehensive evaluation to determine the underlying cause and assess disease severity, with initial testing including urinalysis, 24-hour urine collection, serum albumin, lipid panel, and basic metabolic panel, as well as specific serologic tests and renal biopsy as necessary 1. The diagnosis of nephrotic syndrome is based on the presence of heavy proteinuria (>3.5g/day), hypoalbuminemia, hyperlipidemia, and edema. Initial testing should include:
- Urinalysis with microscopy to evaluate for hematuria, casts, and other abnormalities
- 24-hour urine collection for protein and creatinine clearance to quantify proteinuria
- Serum albumin, lipid panel, and basic metabolic panel to assess for hypoalbuminemia, hyperlipidemia, and other metabolic abnormalities Specific serologic tests should be ordered based on clinical suspicion, including:
- Antinuclear antibodies to evaluate for systemic lupus erythematosus
- Complement levels (C3, C4) to evaluate for complement-mediated diseases
- Hepatitis B and C serologies to evaluate for viral hepatitis
- HIV testing to evaluate for HIV-associated nephropathy
- Serum and urine protein electrophoresis to evaluate for monoclonal gammopathies A renal biopsy is often necessary for definitive diagnosis, particularly in adults or when secondary causes are suspected, as it can provide information on the underlying histopathology and guide treatment decisions 1. Imaging studies such as renal ultrasound may be helpful to evaluate kidney size and rule out obstruction. Additional workup should include assessment for complications of nephrotic syndrome, including hypercoagulability, infections, and medication side effects. The comprehensive approach is necessary because nephrotic syndrome represents a constellation of symptoms rather than a specific disease entity, and early identification of the underlying cause allows for targeted therapy to reduce proteinuria and prevent progression to end-stage renal disease 1.
From the Research
Nephrotic Syndrome Workup
- Nephrotic syndrome is defined by a triad of clinical features: oedema, substantial proteinuria (> 3.5 g/24 hours) and hypoalbuminaemia (< 30 g/L) 2
- The diagnosis of nephrotic syndrome is based on typical clinical features with confirmation of heavy proteinuria and hypoalbuminemia 3
- Proteinuria should be documented by a quantitative measurement e.g. urine protein: creatinine ratio (PCR) or albumin: creatinine ratio (ACR), with PCR > 300-350 mg/mmol indicating nephrotic range proteinuria 2
- A renal biopsy is usually performed to establish what form of glomerular disease is responsible 2, 3
Causes of Nephrotic Syndrome
- The most common cause in children is minimal change glomerulonephritis 2
- In white adults, nephrotic syndrome is most frequently due to membranous nephropathy, whereas in populations of African ancestry the most common cause of nephrotic syndrome is focal segmental glomerulosclerosis 2
- Diabetic nephropathy is the most common multisystem disease that can cause nephrotic syndrome 2, 4
Evaluation and Management
- Patients typically present with periorbital oedema or dependent pitting oedema, and fatigue 3
- Urgent referral to a nephrologist (ideally within 2 weeks) is necessary 2
- Treatment consisting of sodium restriction, fluid restriction, loop diuretics, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, and careful assessment for possible disease complications is appropriate for most patients 3
- Immunosuppressive treatment, including corticosteroids, is often used for nephrotic syndrome, although evidence is lacking 3