Management of Recurrent C3 Glomerulopathy After Kidney Transplantation

Abstract

C3 glomerulopathy (C3G) is an ultra-rare, complement-mediated glomerular disease characterized by dysregulation of the alternative complement pathway and a high propensity for recurrence after kidney transplantation. Although kidney transplantation remains the optimal treatment for patients reaching kidney failure, post-transplant recurrence continues to be a major cause of graft dysfunction and loss. Over the past decade, improved histopathologic recognition and the increasing adoption of protocol biopsies have revealed that C3G frequently recurs early after transplantation, often in a subclinical form. At present, no validated clinical, genetic, or functional biomarkers reliably predict recurrence, and preventive strategies remain unproven. Consequently, from our standpoint, management of recurrent C3G requires a pragmatic, surveillance-driven approach rather than prophylactic intervention. In this review, we provide a practical framework for managing recurrent C3G after kidney transplantation, from transplant candidacy and pre-transplant evaluation to post-transplant monitoring and therapeutic decision-making. We discuss the role of protocol biopsies, the limitations of conventional immunosuppression, and the emerging place of proximal complement inhibitors. Finally, we highlight several unmet needs that continue to limit optimal care, including persistent uncertainty about therapeutic goals, management of subclinical histologic recurrence, and interpretation of treatment response. This review reflects a transplant-centered clinical perspective aimed at supporting nephrologists in real-world decision-making.