C3 glomerulopathy in transplant "like yet unlike native": Pathophysiology, recent advances in therapeutics and...

Area of Science:

• Nephrology
• Transplantation Immunology
• Glomerular Diseases

Background:

• Recurrence of glomerular diseases, particularly C3 glomerulopathy (C3G), is a significant challenge post-kidney transplantation.
• C3G demonstrates the highest recurrence rates among post-transplant glomerular diseases, ranging from 30% to 89%.
• Dysregulation of the complement system is the central driver of C3G pathophysiology.

Purpose of the Study:

• To review the recurrence patterns and management strategies for C3G following kidney transplantation.
• To elucidate the complex pathophysiology of C3G, including genetic and acquired factors.
• To discuss diagnostic challenges, risk factors, and emerging therapeutic advancements.

Main Methods:

• Comprehensive literature review of studies on post-transplant C3G.
• Analysis of pathophysiology, diagnostic criteria, and risk factors.
• Evaluation of current and emerging management strategies, including complement-targeted therapies.

Main Results:

• C3G recurrence rates post-transplantation are high (30-89%).
• Complement system dysregulation, influenced by genetic, autoimmune, and acquired factors, underlies C3G.
• Risk factors include ischemia-reperfusion injury, delayed graft function, infections, and monoclonal gammopathy.
• Histopathology in the allograft requires early detection via protocol biopsies.
• Recent FDA approvals of iptacitan and pegcetacoplan mark significant therapeutic progress.

Conclusions:

• Personalized medicine, enhanced biomarkers, and genetic/autoantibody testing are crucial for managing transplant-associated C3G.
• Continued research is vital for refining surveillance and treatment protocols.
• Complement-targeted therapies represent a major advancement in managing C3G recurrence post-transplant.