Clinical Predictors and Prognosis of Recurrent IgA Nephropathy in the Kidney Allograft

Abstract

Introduction: Although IgA nephropathy (IgAN) is the most common recurrent glomerulonephritis encountered in the kidney allograft, the clinical and immunogenetic characteristics remain poorly understood. We sought to study determinants and prognosis of recurrent IgAN with special focus on human leukocyte antigens (HLAs). Materials and Methods: Between 2005 and 2019, we identified 282 transplanted patients with failure secondary to IgAN from 2 North American and 1 European Medical Centers, including 80 with recurrent IgAN and 202 without recurrence. The prevalence of HLAs was compared to external healthy controls of European ancestry ( n = 15,740). Graft survival was assessed by the Kaplan-Meier method and log rank test. Cox proportional hazards were used for multivariable analyses. Results: Compared to external controls of European ancestry, kidney transplant recipients of European ancestry with kidney failure secondary to IgAN had higher frequency of HLA-DQ5 (42% vs. 30%, OR = 1.68, p = 0.002) and lower frequency of HLA-DR15 (15% vs. 28%, OR = 0.46, p < 0.001) and HLA-DQ6 (32% vs. 45%, OR = 0.59, p = 0.003); however, the frequency of these HLAs were similar in recurrent versus nonrecurring IgAN. Younger recipient age at transplantation was an independent predictor of recurrence. HLA matching was an independent predictor for recurrent IgAN only in recipients of living-related but not deceased or living-unrelated transplants. Recurrent IgAN was an independent predictor of allograft failure, along with acute rejection. In patients with recurrent IgAN, serum creatinine at biopsy, degree of proteinuria, and concurrent acute rejection were associated with inferior allograft survival. Conclusion: Recurrent IgAN negatively affects allograft survival. Younger recipient age at transplantation is an independent predictor of recurrent IgAN, while the presence of HLAs associated with IgAN in the native kidney and HLA matching in recipients of deceased or living-unrelated transplants are not.