Cardiovascular Risk in Kidney Transplant Recipients Receiving Mammalian Target of Rapamycin Inhibitors

Abstract

Cardiovascular diseases (CVD) are the leading cause of mortality in renal transplant recipients. Various traditional and unconventional cardiovascular risk factors are potentiated by the adverse effects of immunosuppressive drugs. The mammalian target of rapamycin (mTOR) inhibitors have shown cardioprotective effects in experimental studies, but their influence on CVD in renal transplantation is unclear. The study included 115 kidney transplant recipients treated with mTOR inhibitors with steroids. A group of 38 patients received additionally small doses of calcineurin inhibitor. The control group consisted of 58 kidney transplant recipients randomly chosen among the population of patients transplanted at the same time, who received a calcineurin inhibitor, mycophenolate mofetil or sodium plus steroids. No differences in age, gender, duration of pretransplantat dialysis, time after transplantation, body mass index or glycated hemoglobin existed between the groups. Blood pressure and number of antihypertensive agents, high-density lipoprotein cholesterol, and uric acid levels were similar. The prevalence of diabetic, ischemic, or hypertensive nephropathy as the reason for end-stage renal disease was similar ( P = .08). The study group showed higher mean values of total cholesterol (249 vs 204.6 mg/dL; P < .0001) and low-density lipoprotein 136.5 vs 117.7 mg/dL; ( P = .015), as well as median values of triglycerides (202 vs 142 mg/dL; P < .0001) and proteinuria ( P = .0002). mean estimated glomerular filtration rate was lower in the study group (42.9 vs 51.9 mL/min; P = .0003). Posttransplant diabetes appeared in 38% of the study group compared to 20% of the controls ( P = .08). The incidence of coronary artery disease was higher among patients treated with mTOR inhibitors ( P = .04). CVD, defined as myocardial infarction, percutaneous coronary intervention, stroke, aortic aneurysm, pulmonary thromboembolism, sudden cardiac death appeared in 26 study group compared with four control patients ( P = .24). The risk of any CVD was not significantly higher among patients receiving mTOR inhibitors hazard ratio 1.94; 95% confidence interval 0.83–4.52). In conclusion, no correlation was observed between the duration of mTOR therapy and CVD.