What is the initial workup for Nephrotic Syndrome (a condition characterized by severe proteinuria, hypoalbuminemia, hyperlipidemia, and edema)?

From the Guidelines

The initial workup for nephrotic syndrome should include a comprehensive evaluation to determine the underlying cause and assess disease severity, starting with a thorough history and physical examination, and laboratory testing including urinalysis, urine protein-to-creatinine ratio, serum albumin, lipid panel, and renal function tests. This approach is crucial in identifying the underlying cause of nephrotic syndrome and guiding specific treatment approaches. According to the KDIGO practice guideline on glomerulonephritis 1, the initial evaluation should focus on determining the presence of nephrotic-range proteinuria, which is defined as urinary protein excretion exceeding 3.5g/day.

The initial workup should include:

• A thorough history and physical examination, focusing on medication use, systemic diseases, and family history of kidney disease
• Laboratory testing, including:
  • Urinalysis with microscopy
  • Urine protein-to-creatinine ratio or 24-hour urine protein
  • Serum albumin
  • Lipid panel
  • Renal function tests (BUN, creatinine, eGFR)
  • Complete blood count
  • Serum electrolytes
  • Liver function tests
• Serologic testing, including:
  • Complement levels (C3, C4)
  • Antinuclear antibody
  • Anti-double stranded DNA
  • Hepatitis B and C serologies
  • HIV testing
  • Serum and urine protein electrophoresis (to rule out multiple myeloma)
• Imaging studies, including renal ultrasound to assess kidney size and structure
• A kidney biopsy is often necessary to determine the specific glomerular pathology, especially in adults, those with atypical presentations, or when secondary causes are suspected 1.

While awaiting definitive diagnosis, supportive care should be initiated, including sodium restriction, fluid restriction if edema is severe, and diuretics for edema management. Thromboprophylaxis with anticoagulation may be considered in severe cases due to the hypercoagulable state associated with nephrotic syndrome. The KDIGO guideline recommends starting immunosuppressive therapy in patients with nephrotic syndrome when certain conditions are met, such as persistent proteinuria exceeding 4g/day or the presence of severe, disabling, or life-threatening symptoms related to the nephrotic syndrome 1.

From the Research

Initial Workup for Nephrotic Syndrome

The initial workup for nephrotic syndrome typically involves:

• Documenting proteinuria through a quantitative measurement, such as urine protein: creatinine ratio (PCR) or albumin: creatinine ratio (ACR) 2
• Assessing for hypoalbuminemia (< 30 g/L) and hyperlipidemia 3, 4, 2, 5
• Evaluating for signs of venous thrombosis and infection 3, 4, 2, 5
• Considering secondary causes, such as diabetes mellitus, systemic lupus erythematosus, and medication adverse effects 3, 4, 2, 5

Diagnostic Tests

Diagnostic tests may include:

• Urine tests to quantify proteinuria and assess for hematuria 2
• Blood tests to evaluate renal function, electrolyte levels, and liver function 3, 5
• Imaging studies are generally not needed, but may be used in select cases to evaluate for complications or secondary causes 5
• Renal biopsy may be useful in some cases to confirm an underlying disease or to identify idiopathic disease that is more likely to respond to corticosteroids 3, 2, 5

Referral to a Nephrologist

Referral to a nephrologist is often necessary, especially in cases where:

• The diagnosis is uncertain or complex 3, 2
• Renal biopsy is indicated 2
• Immunosuppressive treatment is being considered 3, 4
• There are concerns about potential complications, such as venous thrombosis or infection 3, 4, 2, 5