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Published on: October 11, 2014
Management of Recurrent C3 Glomerulopathy After Kidney Transplantation
Hernando Trujillo1,2, Teresa Cavero1,2, Sarah M Moran3
1Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain.
Insights
C3 glomerulopathy (C3G) management after kidney transplant focuses on surveillance, not prevention, due to frequent early recurrence. This review offers a practical framework for transplant-centered care, addressing monitoring and treatment decisions.
Area of Science:
- Nephrology
- Complement Immunology
- Transplantation
Background:
- C3 glomerulopathy (C3G) is a rare, complement-mediated kidney disease.
- Alternative complement pathway dysregulation drives C3G pathogenesis.
- Recurrence post-kidney transplant is common, leading to graft loss.
Purpose of the Study:
- To provide a practical framework for managing recurrent C3G post-kidney transplantation.
- To guide nephrologists in transplant candidacy, evaluation, monitoring, and treatment.
- To discuss current challenges and emerging therapies for C3G recurrence.
Main Methods:
- Review of current literature and clinical perspectives on C3G recurrence.
- Discussion of histopathologic findings, including protocol biopsies.
- Analysis of management strategies, from surveillance to therapeutic interventions.
Main Results:
- C3G frequently recurs early and often subclinically after kidney transplantation.
- No reliable biomarkers currently predict C3G recurrence.
- A surveillance-driven approach is recommended over prophylactic intervention.
Conclusions:
- Management of recurrent C3G necessitates a pragmatic, surveillance-focused strategy.
- Emerging therapies like proximal complement inhibitors show promise.
- Further research is needed to address therapeutic goals and treatment response interpretation.
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.
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