What are the diagnostic criteria and initial management for nephrotic syndrome?

Diagnostic Criteria and Initial Management for Nephrotic Syndrome

Nephrotic syndrome is defined by the presence of proteinuria (≥3.5 g/24h), hypoalbuminemia (<3.0 g/dL), edema, and often hyperlipidemia. 1, 2

Diagnostic Criteria

Essential Components

• Proteinuria:

  • Adults: ≥3.5 g/24h or spot urine protein-to-creatinine ratio (UPCR) ≥300-350 mg/mmol 2
  • Children: First morning UPCR ≥2 g/g or ≥40 mg/h/m² 3

• Hypoalbuminemia:

  • Adults: <3.0 g/dL 3
  • Children: ≤2.5 g/dL (traditional definition) 3

Associated Features

• Edema (periorbital, dependent pitting)
• Hyperlipidemia (hypercholesterolemia, hypertriglyceridemia)
• Lipiduria

Special Considerations

• In some cases, nephrotic syndrome may present without reaching the 3.5 g/24h proteinuria threshold, particularly when concurrent liver disease affects albumin synthesis 4
• The risk of venous thromboembolic events increases when serum albumin falls below 2.9 g/dL 3

Initial Evaluation

Laboratory Tests

1. Urine Studies:

   • Quantitative proteinuria measurement (24-hour collection or spot UPCR)
   • Urinalysis for lipiduria and cellular elements

2. Blood Tests:

   • Serum albumin
   • Lipid profile (total cholesterol, triglycerides)
   • Renal function (creatinine, BUN, eGFR)
   • Serum electrolytes
   • Coagulation profile

Etiological Workup

1. Secondary Causes Assessment:

   • Diabetes mellitus (HbA1c, fasting glucose)
   • Systemic lupus erythematosus (ANA, anti-dsDNA)
   • Hepatitis B and C serology 5
   • HIV testing
   • Serum and urine protein electrophoresis (for amyloidosis, multiple myeloma)

2. Primary Glomerular Disease Evaluation:

   • Anti-PLA2R antibodies (for membranous nephropathy) 5
   • Kidney biopsy (indicated in adults and in children who don't respond to initial steroid therapy) 6

Initial Management

Conservative Management

1. Edema Control:

   • Dietary sodium restriction
   • Diuretics (loop diuretics often required due to resistance)
   • Monitor for intravascular volume depletion

2. Proteinuria Reduction:

   • ACE inhibitors or ARBs 5
   • Optimize blood pressure control

3. Thromboembolism Prophylaxis:

   • Consider anticoagulation in high-risk patients, particularly those with:
     • Serum albumin <2.9 g/dL 3
     • Membranous nephropathy 6
   • Note: Direct oral anticoagulants are not recommended; use standard VTE dosing when anticoagulation is indicated 3

4. Infection Prevention:

   • Consider infection prophylaxis in severe cases
   • Ensure appropriate vaccinations

Disease-Specific Treatment

Children

• Initial Treatment: Oral glucocorticoids for 8-12 weeks (4-6 weeks daily followed by 4-6 weeks alternate-day) 3
• Response Assessment: If no improvement, consider genetic testing and kidney biopsy 6

Adults

• Treatment Initiation Criteria (for membranous nephropathy) 3:

  1. Urinary protein excretion >4 g/d AND >50% of baseline value after 6 months of conservative therapy, OR
  2. Severe, disabling symptoms related to nephrotic syndrome, OR
  3. Serum creatinine rise ≥30% within 6-12 months (with eGFR ≥25-30 ml/min/1.73m²)

• Treatment Options based on biopsy findings:

  • Membranous nephropathy: Cyclophosphamide/corticosteroids or calcineurin inhibitors 3
  • FSGS: Corticosteroids, calcineurin inhibitors, or rituximab 3
  • Minimal change disease: Corticosteroids

Important Caveats

• Kidney Biopsy Timing: In adults, perform early unless anti-PLA2R antibodies are positive (diagnostic of membranous nephropathy) 6
• Albumin Assay Variation: Be aware that bromocresol green (BCG) overestimates serum albumin in nephrotic syndrome compared to bromocresol purple (BCP) 3
• Treatment Response: Remission may take up to 12-24 months in conditions like membranous nephropathy 3
• Secondary Causes: Always exclude secondary causes before diagnosing primary glomerular disease 2