Advancing Treatment for C3G; Targeting the Complement System for Personalized Kidney Care - Episode 15
Managing Recurrent C3G for Patients Post Kidney Transplant
Panelists discuss how early protocol biopsies and proactive monitoring post-transplant can reveal subclinical recurrence of C3 glomerulopathy (C3G), prompting consideration of timely initiation of complement-targeting therapies to preserve graft function.
Video content above is prompted by the following:
Posttransplant Management of C3G
Key Discussion Points:
- High Risk of Recurrence:
C3G is associated with a high rate of recurrence post-transplant, even in patients who exhibit stable clinical parameters (normal glomerular filtration rate, no proteinuria or hematuria). Histologic recurrence may be detectable early via immunofluorescence and EM, often preceding changes on light microscopy. - Importance of Protocol Biopsies:
Data from Andrew S. Bomback, MD, MPH, and group suggest that performing protocol biopsies at 6-, 1-, and 24-months post-transplant reveals subclinical recurrence in most patients. These findings emphasize the progressive nature of C3G despite a lack of overt clinical signs. - Early Therapeutic Intervention:
The panel agrees that early treatment with complement inhibitors, such as iptacopan, may be beneficial—even in the absence of proteinuria or hematuria. The FDA label for iptacopan allows treatment initiation based solely on histologic diagnosis of C3G, independent of proteinuria thresholds. - Guidance on Treatment Timing:
In the absence of data from randomized controlled trials, clinicians are encouraged to consider:- Initiating complement inhibitors preemptively at or before transplant (analogous to atypical = hemolytic uremic syndrome management), or
- Using the first protocol biopsy (typically at 6 months) to guide the start of therapy if histologic recurrence is present
- Collaboration Between General Neurology and Transplant Teams:
As C3G and other glomerular diseases present complex post-transplant challenges, there is a growing need for closer collaboration between glomerular disease specialists and transplant nephrologists. This includes:- Shared decision-making for high-risk patients
- Joint planning for surveillance and treatment strategies
- Raising awareness about the significance of subtle clinical signs and the utility of early biopsy
Looking Ahead:
The field is evolving, and more studies comparing early vs delayed initiation of complement inhibitors are needed. Until then, clinicians are urged to adopt a proactive, not reactive, approach to surveillance and management of recurrent C3G in transplant recipients.
