Table 1.

Suggested step-wise approach to the evaluation of NS in an older adult (>65 years of age)

Step 1. Initial studies
 Perform a complete history and physical examination, emphasizing family history, medication use, infection history, and assessment of systemic manifestations
 Perform a urinalysis and microscopically examine a freshly obtained urine sediment
 Confirm NS with 24-hour urine protein (>3.5 g/d) or spot urine protein/creatinine ratio (>3.0) and serum albumin <3.4 g/dl
 Measure serum creatinine concentration and calculate estimated GFR
 Measure a serum biochemical profile, fasting lipids, and a complete blood count
 Measure hemoglobin A1c and examine the retina with dilated pupils (if patient has diabetes)
 Measure serum-free light chains and perform a serum and urine immunofixation test for monoclonal proteins. Consider an abdominal fat pad biopsy/aspiration if amyloidosis is suspected
 Assess renal size and configuration by abdominal ultrasound
Step 2. Perform a kidney biopsy, if no contraindications exist, with complete histopathological assessment with light, immunofluorescence, and electron microscopic studies (including a Congo red stain if appropriate)
Step 3. Targeted evaluation based on glomerular and extraglomerular lesions if a lesion of MN is found by renal biopsy
 Measure hepatitis B surface antigen and hepatitis C antibody
 Measure antinuclear antibody and anti-DNA antibody (particularly if features of SLE are noted on biopsy)
 Measure serum C3 and C4 complement
 Measure anti-PLA2R autoantibody (Western blot or alternative if available)
 Request immunofluorescence for IgG subclass deposition
 Request immunofluorescence for PLA2R deposits (if available)
 If IgG4+ and anti-PLA2R + (serum and or glomerular deposits), consider the most likely diagnosis is primary idiopathic MN and manage accordingly
 If IgG1–3 dominant and IgG4 weak or absent, regardless of the results with anti-PLA2R, consider the possibility of an underlying neoplasia.
Step 4. Evaluate for suspected underlying malignancy if appropriate based on step 4 findings or a suspicious history or physical examination
 Conduct a computed tomography scan of the chest, especially in patients with a smoking history
 Check stool for occult blood and arrange for colonoscopy if not already done as part of routine preventative care
 In women, perform a breast examination and mammography if not already done as part of routine preventative care
 In men, perform a rectal examination and prostate-specific antigen if not already done as part of routine preventative care
 Consider abdominal computerized tomography (CT) scan to evaluate for subdiaphragmatic neoplastic processes (i.e., renal cell carcinoma. lymphoma, etc.)
  • NS, nephrotic syndrome; MN, membranous nephropathy; anti-PLA2R, antiphospholipase A2-receptor.