IgA Nephropathy
A kidney disease where abnormal IgA proteins build up in the kidney filters, causing blood in the urine and potential long-term kidney failure.
Emergency Management: Rapidly Progressive Glomerulonephritis (RPGN). Requires urgent renal biopsy, pulse IV methylprednisolone, and cyclophosphamide.
IgA Nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, characterized by the predominant deposition of polymeric immunoglobulin A1 (IgA1) in the glomerular mesangium, leading to mesangial proliferation and hematuria.
Detailed Overview
IgAN typically presents in young adults with episodic macroscopic hematuria concurrent with mucosal (e.g., upper respiratory) infections (synpharyngitic hematuria), or as microscopic hematuria found incidentally. The pathogenesis involves a multi-hit process starting with galactose-deficient IgA1. While many have a benign course, roughly 30-40% progress to End-Stage Renal Disease (ESRD) over 20 years. Treatment focuses on blood pressure control and reducing proteinuria with RAAS blockade.
Epidemiology & Demographics
Most common glomerulonephritis globally. Peak incidence in the 20s and 30s. More common in males (2:1) and populations of East Asian and Caucasian descent.
Etiological Mechanism
Autoimmune condition triggered by abnormal IgA1 glycosylation.
Primary Causes
Galactose-deficient IgA1 immune complex deposition
The '4-hit hypothesis': 1) Production of galactose-deficient IgA1 (Gd-IgA1). 2) Synthesis of autoantibodies against Gd-IgA1. 3) Formation of pathogenic immune complexes in the circulation. 4) Deposition of these complexes in the glomerular mesangium, triggering complement activation, mesangial cell proliferation, and release of profibrotic cytokines leading to glomerulosclerosis.
Diagnostic Criteria & Guidelines
Renal biopsy showing prominent, global IgA deposits in the mesangium on immunofluorescence.
Optimized supportive care: ACE inhibitor (Lisinopril 10-40 mg daily) or ARB (Losartan 50-100 mg daily) titrated to maximum tolerated dose to control BP < 120/80 and reduce proteinuria to < 1 g/day. SGLT2 inhibitors (Dapagliflozin 10 mg daily) for added nephroprotection.
Second-Line & Adjunctive Therapy
For persistent proteinuria > 1 g/day despite 3-6 months of optimized supportive care: Systemic corticosteroids (Prednisone 1 mg/kg/day for 2 months, then taper) OR Targeted release Budesonide (Tarpeyo) 16 mg PO daily for 9 months.
Surgical & Procedural Management
Kidney transplantation for ESRD. (Note: IgAN can recur in the allograft in ~30% of cases).
Patient Counseling & Advice
Reassure that gross hematuria during colds is typical and usually resolves. Emphasize strict adherence to BP medications, as hypertension heavily drives disease progression.
Follow-Up & Monitoring Schedule
Check BP, eGFR, and Urine Protein-to-Creatinine Ratio (UPCR) every 3-6 months.
Preventive Strategies
None.
Highly variable. 30-40% progress to ESRD over 20-25 years. Proteinuria > 1 g/day and hypertension are the strongest predictors of poor outcome.