What is IgA Nephropathy?
IgA nephropathy (IgAN), also known as Berger's disease, is the most common primary immune-mediated glomerular disease worldwide, characterized by the deposition of IgA-dominant immune complexes in the glomerular mesangium, leading to glomerular inflammation, scarring, and progressive kidney disease. 1
Pathophysiology
The disease develops through a specific pathogenic mechanism:
- Abnormal IgA1 production: Patients produce polymeric, undergalactosylated IgA1 molecules that form immune complexes 2, 3
- Mesangial deposition: These IgA-containing immune complexes deposit in the glomerular mesangium, the definitive diagnostic feature of the disease 4
- Glomerular injury: The deposits trigger mesangial cell proliferation, inflammation, and eventual glomerulosclerosis 1
- Receptor involvement: Functional abnormalities of IgA receptors (CD89 on myeloid cells and CD71 on mesangial cells) facilitate complex formation and mesangial trapping 2, 3
Clinical Presentation
IgAN presents with variable manifestations, typically in younger adults (mean age 34-45 years) 1:
- Asymptomatic microscopic hematuria: Approximately 60% of cases are detected incidentally with hematuria or proteinuria on routine urinalysis 1
- Episodic gross hematuria: Occurs in 40-50% of patients, characteristically following upper respiratory infections (synpharyngitic hematuria) 4, 1
- Nephritic syndrome: The typical presentation pattern with hematuria, proteinuria, and variable degrees of kidney dysfunction 1
- Nephrotic syndrome: Less common, occurring in <5% of cases 1
- Rapidly progressive glomerulonephritis: Rare presentation (<5%) with extensive crescent formation (usually >50% of glomeruli) and rapid kidney function decline 5, 1
Diagnosis
The diagnosis requires kidney biopsy demonstrating IgA-dominant or co-dominant immune deposits in the glomerular mesangium 4:
- Biopsy indication: Adults with suspected IgAN and proteinuria ≥0.5 g/day should undergo kidney biopsy 1
- Immunofluorescence: Shows mesangial IgA deposits as the dominant or co-dominant immunoglobulin 4
- Electron microscopy: Reveals electron-dense deposits in the mesangium, often with C3 co-deposition 4
- Exclusion of secondary causes: Must rule out IgA vasculitis, infection-related glomerulonephritis, cirrhosis, inflammatory bowel disease, celiac disease, and autoimmune diseases 4, 1
Prognosis
IgAN is not a benign disease—up to 50% of patients develop kidney failure within 10 years of diagnosis, and 20-40% progress to end-stage renal disease within 5-25 years 1, 6:
- Clinical risk factors: Elevated serum creatinine at presentation, uncontrolled hypertension, and persistent proteinuria >1 g/day predict progression 4, 6
- Histologic predictors: Glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescent formation, and severity of tubulointerstitial lesions correlate with worse outcomes 6
- Risk stratification tools: The MEST-C scoring system (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescents) and International IgAN Prediction Tool provide prognostic information 5