Definitive Diagnosis of IgA Nephropathy
A kidney biopsy is the only method to definitively diagnose IgA nephropathy—there are no validated serum or urine biomarkers that can establish this diagnosis. 1
Essential Diagnostic Requirements
Kidney Biopsy is Mandatory
- IgA nephropathy can only be diagnosed with a kidney biopsy. 1
- The biopsy is essential and irreplaceable for establishing the diagnosis, as clinical presentation alone cannot confirm IgAN. 2
- No validated diagnostic serum or urine biomarkers exist for IgAN, despite ongoing research into galactose-deficient IgA1 and glycan-specific autoantibodies. 1, 3
Required Immunofluorescence Studies
- Immunofluorescence (IF) studies using antibodies to IgG, IgM, IgA, kappa, and lambda are mandatory to detect immunoglobulin deposits in the kidney. 1
- Immunohistochemistry can serve as an alternative to IF using the same antibody panel. 1
- The hallmark finding is dominant or co-dominant mesangial IgA deposition on immunofluorescence microscopy. 1
Mandatory Histologic Scoring
- Determine the MEST-C score according to the revised Oxford Classification for every IgAN biopsy: 1
- M = Mesangial hypercellularity
- E = Endocapillary hypercellularity
- S = Segmental sclerosis
- T = Interstitial fibrosis/tubular atrophy
- C = Crescents
- This scoring system provides valuable prognostic information independent of clinical characteristics and should always be reported. 1
Critical Differential Diagnosis Considerations
Exclude Secondary Causes
- Assess all patients with IgAN for secondary causes before confirming primary IgAN. 1
- Secondary IgAN can be triggered by chronic inflammatory bowel disease, infections, tumors, or rheumatic diseases. 4
- In adults, especially older men, consider screening for malignancy as IgAN can be a paraneoplastic manifestation associated with monoclonal IgA gammopathy or multiple myeloma. 5
Rule Out Monoclonal Immunoglobulin Deposition
- Correlate all immunoglobulin deposits detected by kidney biopsy with serum and urine tests for monoclonal immunoglobulin, including serum protein electrophoresis with immunofixation and 24-hour urine protein electrophoresis with immunofixation. 1
- Congo red staining is strongly advised in all patients with serum/urine monoclonal immunoglobulin to exclude amyloidosis. 1
Clinical Context for Biopsy Decision
When to Pursue Kidney Biopsy
- Patients with higher levels of proteinuria or diminished/worsening eGFR warrant a kidney biopsy to confirm diagnosis and determine risk stratification. 1
- Patients with preserved eGFR and proteinuria <500 mg/g require individualized discussion about biopsy utility versus watchful waiting with anti-proteinuric therapy. 1
- More severe or advanced disease presentations necessitate biopsy for both diagnostic and prognostic purposes, especially when considering immunosuppressive therapy. 1
Common Pitfalls to Avoid
- Do not rely on clinical presentation alone: Characteristic findings like nephritic urinary sediment (erythrocytes, acanthocytes, erythrocyte casts), proteinuria, or intermittent macrohematuria during upper respiratory infections are suggestive but not diagnostic. 4
- Do not use serum IgA levels for diagnosis: While research continues on galactose-deficient IgA1 as a potential biomarker, these tests are not validated for clinical diagnosis. 3, 6
- Do not skip the MEST-C scoring: This is essential for prognosis and treatment planning, not just for diagnosis. 1
- Do not forget to evaluate for secondary causes: Missing an underlying malignancy, infection, or autoimmune disease can lead to inappropriate treatment. 1, 4