What serologies to check for a patient with proteinuria (Urinary Protein-to-Creatinine Ratio (UPCR)) of 2.1 and no hematuria (blood in urine)?

Serological Evaluation for Proteinuria with UPCR 2.1 and No Hematuria

For a patient with proteinuria (UPCR 2.1) and no hematuria, a comprehensive serological workup should include glomerulonephritis screening with ANA, complement levels (C3, C4), ANCA, anti-GBM antibodies, hepatitis B and C testing, HIV, immunoglobulins, and protein electrophoresis. 1

Classification of Proteinuria

The UPCR of 2.1 represents:

• Severely increased albuminuria (Category A3) 1
• Above the threshold for nephrotic-range proteinuria (>2.0 g/g) 2
• Significant risk for kidney disease progression 1

Recommended Serological Testing

Primary Tests (First-line):

• Glomerulonephritis (GN) screen 1:
  • Antinuclear antibody (ANA)
  • Complement levels (C3, C4)
  • Anti-neutrophil cytoplasmic antibody (ANCA)
  • Anti-glomerular basement membrane (anti-GBM) antibodies
  • Hepatitis B and C serology
  • HIV testing
  • Immunoglobulins and protein electrophoresis

Additional Tests Based on Clinical Suspicion:

• For suspected lupus nephritis:

  • Anti-dsDNA antibodies
  • Anti-C1q antibodies (if available) 1
  • Antiphospholipid antibodies 1

• For suspected multiple myeloma (especially in older patients):

  • Serum free light chain assay
  • Serum protein electrophoresis (SPEP)
  • Serum immunofixation electrophoresis (SIFE) 1

Diagnostic Approach Based on UPCR Level

With a UPCR of 2.1 g/g and no hematuria:

1. Lupus nephritis consideration:

   • This level of proteinuria without hematuria could represent class V (membranous) lupus nephritis 1
   • Low complement levels and anti-dsDNA antibodies would support this diagnosis 3

2. Primary glomerular diseases:

   • Membranous nephropathy (check PLA2R antibodies if available)
   • Focal segmental glomerulosclerosis
   • Minimal change disease

3. Systemic diseases:

   • Diabetic nephropathy (check HbA1c)
   • Amyloidosis (consider serum free light chains)

Important Considerations

• The absence of hematuria makes certain glomerulonephritides less likely but does not exclude them
• A UPCR of 2.1 represents significant proteinuria that warrants thorough investigation
• Patients with this level of proteinuria have a high risk of progression to overt kidney disease 3
• Early nephrology referral is recommended for consideration of kidney biopsy 1

Follow-up Testing

• Monitor UPCR every 3-6 months to assess treatment response 4
• Consider kidney biopsy if:
  • Serological tests suggest specific glomerular disease
  • Proteinuria persists despite appropriate therapy
  • Kidney function declines

Pitfalls to Avoid

• Do not rely solely on dipstick testing for protein quantification as it can be affected by urine concentration 5
• Do not assume diabetic nephropathy in patients with diabetes without excluding other causes of proteinuria
• Do not delay serological testing as early identification of treatable causes can prevent irreversible kidney damage 3
• Do not ignore proteinuria even in the absence of hematuria, as it can indicate serious kidney disease 1

Remember that a UPCR of 2.1 without hematuria represents significant proteinuria that requires thorough investigation and likely nephrology referral for consideration of kidney biopsy.