HLA Associations in IgA Nephropathy and Focal and Segmental Glomerulosclerosis

Twenty percent of patients initiating Medicare-supported end-stage renal disease (ESRD) therapy in the United States have chronic glomerulonephritis-induced ESRD. IgA nephropathy (IgAN) and focal and segmental glomerulosclerosis (FSGS) likely account for many of these incident dialysis cases, although patients presenting with advanced renal insufficiency may not receive renal biopsies. To determine whether HLA phenotype associations existed in the subset of IgAN and FSGS patients who develop ESRD, we analyzed HLA frequencies by race in patients with these etiologies of ESRD entered in the South Eastern Organ Procurement Foundation (SEOPF) database. Serologically determined HLA frequencies from 605 renal transplant recipients with ESRD due to FSGS and 196 renal transplant recipients with ESRD due to IgAN were compared with those of 4,506 race-matched cadaveric kidney-donor controls. Race-specific odds ratios (ORs) were calculated and fitted into a log-linear model to determine associations between the HLA system and ESRD due to IgAN and FSGS. Values reported were considered significant (P < 0.05) after Bonferroni correction for multiple comparisons. HLA-1327 and HLA-DR1 frequencies were increased and HLA-DR2 frequency was decreased in African-American and white IgAN-induced ESRD cases compared with race-matched controls (race-combined OR of 2.10, 1.89, and 0.57, respectively; all P ≤ 0.004). HLA frequency differences were not observed in FSGS-induced ESRD patients compared with controls. The results of this study indicate that HLA-1327 and HLA-DR1 are positively associated and HLA-DR2 is negatively associated with IgAN-induced ESRD in patients of both races. These associations may be useful in identifying patients with IgAN at increased or decreased risk for developing progressive renal injury. HLA associations do not exist in the subset of patients with FSGS who develop ESRD, suggesting that non- HLA-mediated genetic and/or environmental factors are associated with the risk of progressive renal injury in individuals with FSGS.