Recurrence of immunoglobulin A nephropathy after kidney transplantation: a therapeutic gap in the era of targeted therapies

Immunoglobulin A nephropathy (IgAN) frequently recurs after kidney transplantation and remains an underrecognized cause of allograft loss. Although targeted-release budesonide, B-cell modulators, and complement inhibitors have transformed native IgAN treatment, transplant recipients were excluded from trials, leaving management based largely on case reports, small series, and registry data. Reported recurrence rates range from 10% to 30% at 10–15 years after transplant, depending on biopsy practices and diagnostic criteria. Younger age, preemptive transplantation, and rapid progression to end-stage kidney disease are the most consistent risk factors. Two large registries suggested that maintenance corticosteroids reduce recurrence, but this association was not confirmed in propensity-matched or multicenter studies, and induction immunosuppression was not adequately accounted for. Recurrence significantly worsens graft survival, with hazard ratios for graft loss ranging from 2 to nearly 4. Mechanistically, IgAN is increasingly viewed as a disorder of B-cell and plasma-cell biology driven by the B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) axis, which may explain why T-cell-focused immunosuppression to prevent rejection fails to prevent recurrence. Early experience with B-cell-, plasma-cell-, and complement-targeted therapies after transplantation is encouraging but limited. Progress will require harmonized registries, validated biomarkers, industry collaboration, and dedicated randomized trials in transplant recipients.