What tests are used to diagnose glomerulonephritis besides a urine test?

Diagnostic Tests for Glomerulonephritis Beyond Urinalysis

Kidney biopsy remains the gold standard for diagnosing glomerulonephritis and should be performed in patients with unexplained kidney disease, proteinuria, hematuria, or declining renal function. 1

Essential Diagnostic Workup

Serologic Testing

• ANCA (anti-neutrophil cytoplasmic antibody) should be measured serially in suspected ANCA-associated vasculitis, particularly when evaluating for microscopic polyangiitis or granulomatosis with polyangiitis 1
• Anti-GBM (glomerular basement membrane) antibodies via radioimmunoassay or hemagglutination to detect anti-GBM disease 2
• Complement levels (C3, C4) to identify complement-mediated glomerulonephritis and lupus nephritis 3
• ANA, anti-dsDNA, and other autoantibodies when systemic lupus erythematosus is suspected 4
• Cryoglobulins and hepatitis C serology for cryoglobulinemic glomerulonephritis 1

Renal Function Assessment

• Estimated GFR (eGFR) using the CKD-EPI creatinine equation in adults or modified Schwartz equation in children, as GFR at baseline is the most potent predictor of renal outcome 1
• Serum creatinine with consideration for dietary intake and muscle mass 1
• Cystatin C-based eGFR when creatinine-based estimates are unreliable due to altered creatinine generation or tubular secretion 1

Proteinuria Quantification

• 24-hour urine collection for total protein excretion is the preferred method in adults with glomerulonephritis 1
• First morning protein-creatinine ratio (PCR) is more appropriate in children 1
• Urine protein electrophoresis can differentiate glomerular versus tubular proteinuria and serves as a helpful surrogate parameter for serial evaluation 1

Inflammatory Markers

• CRP and/or ESR should be determined regularly as serologic markers of disease activity, though results must be interpreted in the clinical context 1

Kidney Biopsy Evaluation

The kidney biopsy provides definitive diagnosis and should include: 1

• Light microscopy to identify the pattern of glomerular injury (proliferative, membranoproliferative, crescentic, sclerosing)
• Immunofluorescence microscopy on frozen tissue to detect immune complex deposition patterns (IgA, IgG, IgM, C3, light chains κ and λ)
• Electron microscopy to identify electron-dense deposits, basement membrane abnormalities, and intratubular crystals that may be missed by light microscopy 1
• Pronase immunofluorescence when standard immunofluorescence is negative but monoclonal immunoglobulin-related disease is suspected 1

Advanced Testing When Indicated

• Flow cytometry or immunotyping of bone marrow when monoclonal gammopathy of renal significance (MGRS) is suspected, with sensitivity to detect clones at 10⁻⁴ to 10⁻⁶ cells 1
• Mass spectrometry for renal amyloid typing when immunofluorescence is negative or equivocal 1
• Genetic testing (whole exome sequencing) in selected cases to enhance diagnostic interpretation 1

Critical Pitfalls to Avoid

Do not delay immunosuppressive therapy while awaiting kidney biopsy if the clinical presentation is compatible with ANCA-associated vasculitis and ANCA serology is positive 5

Repeat kidney biopsy should be performed if the information will potentially alter the diagnosis, therapeutic plan, or contribute to prognosis estimation 1

Serial ANCA measurements have inconclusive predictive value for monitoring disease activity in routine clinical practice, though they remain useful in clinical trials 1