Causes of IgA Nephropathy
IgA nephropathy is a primary autoimmune kidney disease of unclear etiology, characterized by dysregulation of the immune system leading to production and deposition of abnormal (under-glycosylated) IgA1 in the glomerular mesangium. 1, 2
Primary vs. Secondary IgA Nephropathy
Primary IgA Nephropathy (Berger's Disease)
- The exact cause remains unknown, but involves a complex autoimmune process where the immune system produces abnormal IgA antibodies that form circulating immune complexes which deposit in the kidney mesangium 1, 2
- The pathogenesis involves generation of circulating IgA immune complexes with chemical and biological characteristics that favor mesangial deposition and accumulation of under-glycosylated IgA1 2
- Ethnicity and epigenetics play a key role in clinical aggressiveness, suggesting genetic predisposition contributes to disease development 3
- This is the most common form of primary glomerulonephritis worldwide, predominantly affecting young males 4, 5
Secondary IgA Nephropathy
You must always assess for secondary causes in all patients with biopsy-proven IgA nephropathy 6, 7. Secondary IgA deposition can occur with:
- Chronic liver disease (particularly cirrhosis) 8, 4
- Chronic inflammatory bowel disease 6, 7
- Infections (including hepatitis B, hepatitis C, HIV, and hepatitis E) 7, 8
- Systemic lupus erythematosus (must be excluded; distinguished by C1q presence in lupus vs. absence in primary IgAN) 6, 7
- Tumors/malignancies 7
- Rheumatic diseases 7
- Alpha-1-antitrypsin deficiency with associated liver disease (particularly in children, where glomerular changes occur in 79% of cases) 8
Pathogenic Mechanisms
The autoimmune process involves:
- Formation of autoimmune complexes containing abnormal IgA1 that are under-glycosylated 1, 2
- Inflammatory processes triggered by mesangial reaction to IgA1 accumulation 1, 2
- Tissue injury leading to glomerulosclerosis and interstitial fibrosis 2
Critical Clinical Pitfall
Do not assume IgA nephropathy is primary based on clinical features alone, as presentation overlaps significantly with other glomerular diseases 6. Always perform a thorough evaluation to exclude secondary causes, particularly liver disease, infections, and systemic inflammatory conditions, before labeling the disease as primary IgA nephropathy 6, 7, 8.