What are the diagnostic criteria for nephrotic syndrome?

Diagnostic Criteria for Nephrotic Syndrome

Nephrotic syndrome is defined by the triad of proteinuria exceeding 3.5 g/24 hours, hypoalbuminemia (<3.0 g/dL), and edema, often accompanied by hyperlipidemia and lipiduria. 1, 2

Core Diagnostic Criteria

• Proteinuria: Urinary protein excretion >3.5 g/24 hours or protein-creatinine ratio (PCR) >300-350 mg/mmol 2

  • For children: Proteinuria ≥40 mg/h/m² or first morning UPCR of ≥2 g/g 1

• Hypoalbuminemia: Serum albumin <3.0 g/dL in adults 1

  • For children: Traditionally defined as ≤2.5 g/dL 1
  • Note: Different albumin assays yield different results - bromocresol green (BCG) overestimates albumin compared to bromocresol purple (BCP) 1

• Edema: Typically periorbital (most noticeable in morning) or dependent pitting edema (more common later in day) 2

Associated Features

• Hyperlipidemia: Elevated total cholesterol (>260 mg/dL) and triglycerides 3, 4
• Lipiduria: Fat bodies in urine 3
• Increased risk of thromboembolism: Especially when serum albumin falls below 2.9 g/dL 1
• Increased susceptibility to infections 2

Diagnostic Evaluation

Laboratory Assessment

• Quantitative proteinuria measurement:

  • 24-hour urine collection for total protein 4
  • Spot urine protein:creatinine ratio (PCR) or albumin:creatinine ratio (ACR) 2
  • PCR >300-350 mg/mmol indicates nephrotic range proteinuria 2

• Blood tests:

  • Serum albumin 1
  • Complete blood count 1
  • Serum electrolytes (sodium, chloride) 1
  • Kidney function tests (creatinine, urea) 1
  • Lipid profile (cholesterol, triglycerides) 1
  • Thyroid function tests (TSH, free T4) 1
  • Serum IgG level 1
  • Calcium, phosphate, alkaline phosphatase, PTH, vitamin D levels 1

Imaging

• Renal ultrasound: To assess kidney echogenicity and size 1
• Abdominal ultrasound: To evaluate for ascites 1
• Cardiac ultrasound: To check for effusions and left ventricular mass 1

Histopathology

• Kidney biopsy: Usually performed in adults to determine the underlying glomerular disease 2
  • Not routinely performed in children at initial presentation as most are presumed to have minimal change disease 1
  • Indicated in children with steroid resistance 1

Special Considerations

• Children vs. Adults: The definition of nephrotic syndrome in children has traditionally used a lower albumin threshold (≤2.5 g/dL) compared to adults (<3.0 g/dL) 1

• Albumin Assay Variability: A serum albumin of 2.5 g/dL with bromocresol green (BCG) equals approximately 2.0 g/dL with bromocresol purple (BCP) or immunonephelometry 1

• Atypical Presentations: Nephrotic syndrome may occasionally present with sub-nephrotic range proteinuria (<3.5 g/24h) when albumin synthesis is decreased due to concurrent liver disease 5

Differential Diagnosis

• Primary glomerular diseases:

  • Minimal change disease (most common in children) 1
  • Membranous nephropathy (most common in white adults) 2
  • Focal segmental glomerulosclerosis (most common in populations of African ancestry) 2

• Secondary causes:

  • Diabetes mellitus (most common systemic cause) 2
  • Systemic lupus erythematosus 2
  • Amyloidosis 2
  • Infections 6
  • Malignancies 6

Management Approach

• Urgent referral to a nephrologist (ideally within 2 weeks) is necessary for proper evaluation and management 2
• Risk assessment for venous thromboembolism should be performed, particularly when serum albumin falls below 2.9 g/dL 1