C4d-positive chronic rejection: a frequent entity with a poor outcome

Area of Science:

• Nephrology
• Immunology
• Transplantation

Background:

• Chronic rejection (CR) is a major cause of kidney graft loss.
• Antibodies are implicated in chronic graft dysfunction.
• C4d staining is a key diagnostic marker for antibody-mediated rejection.

Purpose of the Study:

• To evaluate the prevalence and impact of C4d positivity in chronic allograft nephropathy (CAN).
• To identify clinical factors associated with C4d positivity in CAN.
• To assess the effect of C4d positivity on long-term kidney graft survival.

Main Methods:

• Retrospective analysis of 80 patients with histological CAN (Banff 97).
• Renal biopsies were assessed for C4d deposition in peritubular capillaries.
• Patients were categorized as C4d-negative or C4d-positive.

Main Results:

• C4d positivity was observed in 62.5% of patients.
• C4d+ patients showed higher rates of proteinuria and were more likely to be highly sensitized (PRA).
• Four-year death-censored graft survival was significantly lower in C4d+ patients (50%) compared to C4d- patients (87%).
• Multivariate analysis identified C4d+, high PRA, and vascular intimal proliferation as risks for graft loss.

Conclusions:

• C4d positive chronic rejection is prevalent and associated with poor kidney graft outcomes.
• Proteinuria is a common clinical finding in C4d positive chronic rejection.
• Further research is needed to determine optimal immunosuppressive strategies for C4d+ chronic rejection.