What tests are used to diagnose nephrotic syndrome?

Diagnostic Tests for Nephrotic Syndrome

The gold standard for diagnosing nephrotic syndrome is a 24-hour urine collection for protein quantification, accompanied by measurement of serum albumin, lipid profile, and kidney function tests. 1

Essential Diagnostic Tests

Urine Tests

• 24-hour urine collection for total protein excretion (gold standard)

  • Includes measurement of creatinine excretion to assess collection adequacy 1
  • Nephrotic-range proteinuria defined as >3.5 g/24 hours 2

• Alternative: Spot urine protein/creatinine ratio (PCR)

  • When 24-hour collection is not feasible
  • PCR >300-350 mg/mmol indicates nephrotic-range proteinuria 3
  • For children, first morning PCR ≥2 g/g is considered nephrotic-range 4

• Urinalysis

  • Evaluation of urine sediment for erythrocyte morphology
  • Assessment for red cell casts and/or acanthocytes 4
  • Note: Dipstick testing alone is insufficient for diagnosis 1

Blood Tests

• Serum albumin

  • Adults: <30 g/L indicates hypoalbuminemia 3
  • Children: ≤2.5 g/dL is the traditional cutoff 4
  • Note the assay method: bromocresol green (BCG) overestimates serum albumin in nephrotic syndrome compared to bromocresol purple (BCP) 4

• Lipid profile

  • Fasting lipid panel to assess for hyperlipidemia 1

• Kidney function assessment

  • Serum creatinine
  • eGFR calculation (CKD-EPI equation for adults, modified Schwartz equation for children) 4
  • Serum urea/BUN

• Complete blood count

  • To assess for anemia and other hematologic abnormalities 1

• Serum electrolytes

  • Sodium, potassium, chloride, bicarbonate 1

Additional Testing Based on Clinical Context

Kidney Biopsy

• Indicated in adults with nephrotic syndrome to determine underlying pathology 1

• Analysis should include:

  • Light microscopy
  • Immunofluorescence
  • Electron microscopy
  • Minimum of 8-10 glomeruli for adequate sampling 1

• In children:

  • Not routinely performed at initial presentation if typical features suggest minimal change disease 4
  • Indicated if steroid-resistant, age ≥12 years, or atypical features 4

Serologic Testing (Based on Clinical Suspicion)

• Autoimmune workup:

  • Anti-nuclear antibodies (ANA)
  • Anti-double stranded DNA
  • Complement levels (C3, C4)

• Monoclonal protein evaluation:

  • Serum and urine protein electrophoresis
  • Immunofixation electrophoresis 4

• Infectious disease screening:

  • Hepatitis B and C serology
  • HIV testing
  • Syphilis serology when clinically indicated 4

Special Considerations

For Children

• First morning PCR is preferred over 24-hour collection 4
• Genetic testing is recommended for steroid-resistant nephrotic syndrome 4

For Adults with Suspected Secondary Causes

• Diabetes: HbA1c, fasting glucose
• Amyloidosis: Consider tissue biopsy, serum free light chains
• Systemic lupus: Complete autoimmune panel

Common Pitfalls to Avoid

1. Relying solely on dipstick testing - can miss significant proteinuria 1
2. Using inappropriate albumin cutoffs - different assay methods (BCG vs BCP) can affect results 4
3. Inadequate urine collection - verify with creatinine measurement 1
4. Failure to assess thrombotic risk - nephrotic syndrome increases risk of venous thromboembolism 4
5. Missing orthostatic proteinuria - first morning urine may underestimate 24-hour protein excretion 1

By following this comprehensive diagnostic approach, clinicians can accurately diagnose nephrotic syndrome and identify its underlying cause, allowing for appropriate management and treatment.