What is the initial workup for nephrotic syndrome?

Initial Workup for Nephrotic Syndrome

The initial workup for nephrotic syndrome should include urinalysis, quantitative proteinuria measurement, comprehensive metabolic panel, lipid profile, and serology tests, with kidney biopsy indicated for adults but generally not required for children under 12 years without atypical features. 1

Diagnostic Confirmation

Step 1: Confirm Nephrotic Syndrome

• Verify the presence of all key diagnostic criteria:
  • Proteinuria >3.5g/24h or urine protein:creatinine ratio (PCR) >300-350 mg/mmol 2
  • Hypoalbuminemia (<30 g/L)
  • Edema (periorbital or dependent)
  • Hyperlipidemia (often present)

Step 2: Laboratory Assessment

• Urine studies:

  • Urinalysis with microscopy (look for RBCs, casts)
  • Quantitative proteinuria measurement (24-hour urine collection or spot urine PCR)
  • Urine protein electrophoresis (to characterize protein composition)

• Blood tests:

  • Complete blood count
  • Comprehensive metabolic panel (including electrolytes, BUN, creatinine)
  • Serum albumin
  • Lipid profile (total cholesterol, triglycerides, HDL, LDL)
  • Coagulation studies (if considering thrombotic risk)

Step 3: Etiological Workup

• For all patients:

  • Hepatitis B and C serology
  • HIV testing
  • Antinuclear antibody (ANA)
  • Complement levels (C3, C4)
  • Serum and urine protein electrophoresis (to rule out paraproteinemia)
  • Blood glucose or HbA1c (to screen for diabetes)

• Selective additional testing based on clinical suspicion:

  • Anti-phospholipase A2 receptor antibodies (for suspected membranous nephropathy)
  • Anti-streptolysin O titers (if post-streptococcal disease suspected)
  • Cryoglobulins
  • Anti-neutrophil cytoplasmic antibodies (ANCA)
  • Anti-glomerular basement membrane antibodies

Imaging Studies

• Renal ultrasound: Assess kidney size, echogenicity, and rule out obstruction or structural abnormalities 3
  • Important to differentiate acute kidney injury from chronic kidney disease
  • Normal-sized kidneys do not exclude chronic kidney disease, especially in diabetic nephropathy or infiltrative disorders

Biopsy Considerations

Adults:

• Kidney biopsy is generally indicated for all adult patients with nephrotic syndrome to determine underlying pathology 3, 1
• Urgent referral to nephrology (within 2 weeks) is recommended 2

Children:

• Age <12 years without syndromic features: Initial empiric treatment with glucocorticoids without biopsy 3
• Age ≥12 years or presence of syndromic features: Biopsy and/or genetic testing with referral to specialty center 3
• No response to initial glucocorticoid therapy: Proceed to genetic testing and kidney biopsy 3

Special Considerations

• Genetic testing: Consider in children with steroid-resistant nephrotic syndrome, as 11-30% will have a monogenic cause 3
• Anti-NEP antibody screening: Consider in infants with congenital nephrotic syndrome who have kidney failure at presentation or transient proteinuria that spontaneously resolves 3
• Risk assessment:
  • Evaluate risk of venous thromboembolism and bleeding 3
  • Assess arterial thrombotic risk using Framingham risk score, including previous events and proteinuria 3

Common Pitfalls to Avoid

• Inadequate quantification of proteinuria: Always obtain quantitative measurement rather than relying solely on dipstick
• Missing secondary causes: Systematically evaluate for diabetes, lupus, amyloidosis, and other systemic disorders
• Delaying nephrology referral: Prompt referral is essential for proper evaluation and management
• Overlooking thrombotic risk: Nephrotic syndrome significantly increases risk of venous thromboembolism
• Assuming minimal change disease in all children: Consider genetic testing in steroid-resistant cases

By following this systematic approach to the initial workup of nephrotic syndrome, clinicians can efficiently diagnose the condition, identify underlying causes, and initiate appropriate management to improve morbidity, mortality, and quality of life outcomes.