Kidney Allograft Rejection as an Independent Non-traditional Risk Factor for Post-transplant Cardiovascular Events.

Abstract

Background: Cardiovascular death is the leading cause of mortality in kidney transplant recipients (KTR). While risk factors for post-transplant cardiovascular events (CVE) have been established, previous studies primarily focused on factors at the time of transplantation without integrating post-transplant factors into the analyses. Additionally, most studies were conducted in a mixed population of cyclosporine A and tacrolimus-based immunosuppression, which have different metabolic effects. This study aims to evaluate factors for post-transplant CVE, including both pre- and post-transplant variables, specifically in a population of KTR receiving tacrolimus-based immunosuppression.

Methods: Competing risk regression was performed modelling participant demographics, transplant characteristics, and post-transplant time-updated variables. The primary outcome was the composite of post-transplant CVE, which included myocardial infarction, heart failure, ischemic stroke, peripheral arterial disease, and cardiovascular death.

Results: The incidence of post-transplant CVE was 15.88 per 1,000 patient-years among 553 KTR included in the study. Key factors significantly associated with post-transplant CVE included recipient age, diabetes mellitus status, post-transplant HbA1c, 24-hour urine creatinine clearance, post-transplant serum calcium, and rejection. KTR with a history of T cell-mediated rejection or antibody-mediated rejection were at a 3.0-fold (95% CI 1.22-7.37, p-value 0.016) and 3.38-fold (95% CI 1.13-10.09, p-value 0.029) higher risk for post-transplant CVE, respectively. Compared to models using pre-transplant factors alone, models that included both pre- and post-transplant variables demonstrated significantly higher prediction performance.

Conclusions: Allograft rejections significantly increased the risk of post-transplant CVE. Surveillance protocols for post-transplant CVE should include KTR with a history of allograft rejection, in addition to the traditional high-risk groups.