HLA Alleles and Prognosis of PLA2R-Related Membranous Nephropathy

Background and objectives Associations between HLA alleles and susceptibility to M-type phospholipase A2 receptor (PLA2R)–related membranous nephropathy have been well defined previously in Chinese patients. However, the relationships between HLA alleles and kidney outcome remain unclear. Design, setting, participants, & measurements Five HLA genes (DRB1, DQA1, DQB1, DRB3, and DRB5) were genotyped in a prospective cohort of 392 patients with PLA2R-related membranous nephropathy. The associations between HLA alleles and kidney outcomes were studied. Results A total of 79 HLA alleles were identified in this study. Four HLA alleles, DRB1*13:01 ( n =12; hazard ratio, 3.7; 95% confidence interval, 1.8 to 7.8; P <0.001), DQB1*06:03 ( n =12; hazard ratio, 3.7; 95% confidence interval, 1.8 to 7.8; P <0.001), DRB1*04:05 ( n =12; hazard ratio, 3.8; 95% confidence interval, 1.5 to 9.5; P =0.004), and DQB1*03:02 ( n =21; hazard ratio, 3.1; 95% confidence interval, 1.4 to 6.7; P =0.005), were associated with a ≥40% eGFR decline during follow-up. DRB1*13:01 and DQB1*06:03 were tightly linked with each other. Forty-four of the 392 patients (11%) carried at least one of the four identified risk HLA alleles in this study. Compared with patients who were negative for all risk HLA alleles, those carrying at least one risk HLA allele had a significant risk of a ≥40% eGFR decline during follow-up (hazard ratio, 3.9; 95% confidence interval, 2.3 to 6.7; P <0.001). After adjusting for age, sex, proteinuria, albumin, eGFR, and anti-PLA2R antibody levels, multivariable Cox analysis showed that patients carrying any of the four risk HLA alleles remained associated with a higher risk of a ≥40% decline in eGFR (hazard ratio, 4.1; 95% confidence interval, 2.3 to 7.1; P <0.001). Conclusions Carrying any of the HLA alleles, DRB1*13:01/DQB1*06:03, DRB1*04:05, and DQB1*03:02, was independently associated with poor prognosis in Chinese patients with PLA2R-related membranous nephropathy.