How is the Diagnosis of IgA Nephropathy Made?
IgA nephropathy can only be diagnosed with a kidney biopsy showing mesangial dominant or co-dominant IgA deposition on immunofluorescence microscopy 1, 2.
Diagnostic Algorithm
When to Suspect IgA Nephropathy
Look for these specific clinical presentations:
- Microscopic hematuria with proteinuria (detected incidentally in ~60% of cases) 3
- Episodic visible hematuria occurring during or immediately after upper respiratory or gastrointestinal infections (synpharyngitic hematuria) in up to 30% of patients 3
- Nephrotic syndrome (<5% of cases) 3
- Rapidly progressive glomerulonephritis (<5% of cases) 3
Indications for Kidney Biopsy
Perform kidney biopsy in all adults with suspected IgA nephropathy who have proteinuria ≥0.5 g/day 2, 3. The 2025 KDIGO guideline encourages a more liberal biopsy policy to ensure early diagnosis and prompt treatment 2.
For patients with preserved eGFR and proteinuria <500 mg/g with low suspicion for other glomerular disorders, a patient-centered discussion about biopsy utility is reasonable, with alternatives including watchful waiting and serial monitoring 1.
Required Biopsy Studies
The diagnosis requires three complementary microscopy techniques:
1. Immunofluorescence (Mandatory)
- Must demonstrate mesangial dominant or co-dominant IgA staining (2+ or greater intensity) 4
- IgA staining should be present in the mesangium, either segmentally or globally 4
- Pattern is typically granular 4
- C3 complement is often present; C1q is characteristically absent or scanty (<2+), which helps differentiate from lupus nephritis 4, 5
2. Light Microscopy
- Determine the MEST-C score according to the revised Oxford Classification 1, 2:
- M = Mesangial hypercellularity
- E = Endocapillary hypercellularity
- S = Segmental sclerosis
- T = Interstitial fibrosis/tubular atrophy
- C = Crescents
- This scoring provides prognostic information independent of clinical characteristics 1
3. Electron Microscopy
- Confirms mesangial electron-dense deposits 4
- Helps exclude other glomerular diseases with similar presentations 4
Critical Diagnostic Pitfall
There are no validated diagnostic serum or urine biomarkers for IgA nephropathy 1, 2. While elevated serum IgA levels and serum IgA/C3 ratios may support clinical suspicion, they cannot establish the diagnosis 6. The kidney biopsy remains mandatory.
Exclude Secondary Causes
After confirming IgA-dominant mesangial deposits, assess all patients for secondary causes 1:
- IgA vasculitis (Henoch-Schönlein purpura)
- IgA-dominant infection-related glomerulonephritis
- Cirrhosis
- Inflammatory bowel disease
- Celiac disease
- Chronic infections (viral hepatitis)
- Autoimmune diseases (axial spondyloarthritis) 3
The diagnosis of primary IgA nephropathy is made only after excluding these secondary causes 3.
Distinguishing Features on Immunofluorescence
IgA nephropathy has distinctive immunohistologic characteristics 5:
- High frequency (67%) of greater lambda than kappa light chain staining
- Absent or scanty C1q staining (helps differentiate from lupus nephritis, which shows prominent C1q)
- When using criteria of ≥2+ dominant/co-dominant mesangial IgA with <2+ C1q, diagnostic accuracy reaches 98% 5