MO987: Risk Predictors and Impact of Post-Transplant Cardiovascular Disease in A 20-Year Cohort of Kidney Transplant Recipients
Authors: Austin Chukwu Chukwuma , Garland Shona , Pullerits Kairi , Middleton Rachel , Chinnadurai Rajkumar , A. Kalra Philip 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Although improvement in histocompatibility matching, immunosuppressive therapy and antimicrobial treatment have led to improved long-term allograft survival, cardiovascular diseases (CVD) remain the major cause of morbidity and mortality in kidney transplant recipients (KTR). In addition to the accumulated risks due to chronic kidney disease and dialysis, kidney transplantation conveys its own unique risk factors for CVD. These include the metabolic effects of immunosuppressive treatments such as post-transplant hyperglycaemia, dyslipidaemia and hypertension as well as the effects of suboptimal kidney function including volume overload, anaemia, mineral bone disease and left ventricular hypertrophy. The predictors of cardiovascular diseases in KTR, however, have not been clearly defined.
This study aimed to first ascertain the incidence of post-transplant CVD in those KTR without a prior confirmed history of CVD, then identify the predictors of CVD transplant associated CVD risk factors and finally evaluate the impact of CVD on graft and patient survival in this era of modern immunosuppressive medications.

METHOD
We evaluated 962 KTR transplanted between 2000 and 2020 and followed in a single centre. About 328 KTR with a history of pre transplant CVD were excluded. CVD was defined as a composite of Ischaemic heart disease, myocardial infarction, heart failure, stroke or peripheral vascular disease. Logistic regression analyses were performed to identify the risk predictors of post-transplant CVD. Kaplan–Meier plots and multivariate Cox proportional hazards regression analysis were used to identify and characterize predictors of dialysis free survival.

RESULTS
Among 634 KTR included in the analysis (mean age: 45 ± 15 years), CVD was reported in 101 KTR (16%) during a median follow-up of 95.9 months. About 274(43%) were females, 531(84%) were Caucasians. KTR with post-transplant CVD were likely to be older (50 ± 13 versus 44 ± 15 years; P &lt; 0.001), had spent more time on dialysis [median (IQR) 21 (1–51) versus 11 (0–3) months; P = 0.004] and received cyclosporin maintenance (18% versus 7%; P = 0.01). Incidence of post-transplant CVD was independently predicted by older age [OR: 1.40 (1.15–1.70: P = 0.001)], tacrolimus therapy [OR: 0.81 (0.71–0.93), P = 0.002], mean haemoglobin concentration [OR: 0.86 (0.75–1.00), P = 0.049] and average C-reactive protein (CRP) level [OR: 1.13 (1.02–1.25), P = 0.02] (Figure 1). The median dialysis free survival was significantly lower in KTR who developed post-transplant CVD (14.7 versus 20 years, P = 0.009).
In the multivariate Cox regression analysis, the factors associated with worse dialysis free survival in our cohort (survival with a functioning graft) were older age at transplantation [hazard ratio (HR): 1.03; P &lt; 0.001), a history of post-transplant CVD (HR: 1.68; P = 0.006), higher post-transplant parathormone levels (HR: 1.02; P &lt; 0.001), higher mean urine protein creatinine ratio (uPCR) (HR: 1.003: P &lt; 0.001), a greater annual rise in uPCR (HR: 1.002; P &lt; 0.001) and a history of acute rejection (HR: 1.56; P = 0.03). Statin treatment was associated with better dialysis free survival outcome (HR: 0.60; P = 0.01).

CONCLUSION
The incidence of post-transplant CVD in KTR with no history of pre-transplant CVD was 16%. Age at transplantation and average CRP were independent predictors of post-transplant CVD whereas treatment with Tacrolimus was associated with a lower risk of CVD. Statin therapy was associated with better dialysis free survival whereas a higher PTH was linked to poor survival. It was interesting to note that diabetes was not independently associated with the risk and outcome of post-transplant CVD in our cohort.