IgA Nephropathy

IgA nephropathy (Berger disease) is the most common primary glomerulonephritis worldwide. It is caused by deposition of galactose-deficient IgA1 (Gd-IgA1) in the glomerular mesangium. The pathogenesis involves a multi-hit model: (1) increased production of Gd-IgA1 (abnormally glycosylated IgA1 with exposed N-acetylgalactosamine), (2) formation of anti-glycan IgG or IgA antibodies that recognize the aberrant IgA1, (3) formation of circulating immune complexes, and (4) mesangial deposition of these complexes, activating complement (alternative and lectin pathways) and triggering mesangial cell proliferation, matrix expansion, and glomerular inflammation. The hallmark clinical presentation is synpharyngitic hematuria — episodic gross hematuria (tea-colored or cola-colored urine) occurring within 1-2 DAYS of an upper respiratory infection. This distinguishes it from post-streptococcal glomerulonephritis (PSGN), which occurs 2-3 WEEKS after infection. Between episodes, persistent microscopic hematuria and variable proteinuria are common. IgA nephropathy is NOT a benign disease: 20-40% of patients progress to end-stage renal disease (ESRD) over 20-30 years. Prognostic factors predicting poor outcome include: persistent proteinuria >1 g/day (strongest predictor of progression), hypertension, elevated creatinine at diagnosis, and severity of histological damage on biopsy (Oxford MEST-C classification). Serum IgA levels are elevated in ~50% of cases but are NOT diagnostic. Definitive diagnosis requires renal biopsy showing mesangial IgA deposits on immunofluorescence (IF) microscopy — this is pathognomonic.