Cardiac response to early conversion from calcineurin inhibitor to everolimus in renal transplant recipients--a three-yr serial echocardiographic substudy of the randomized controlled CENTRAL trial

Abstract

Background: In transplant recipients, calcineurin inhibitors (CNIs) are associated with adverse cardiac effects while mTOR inhibitors have been reported to be beneficial. We performed a randomized controlled trial (RCT) in de novo renal transplant recipients examining cardiac responses of everolimus vs. CNI.

Methods: This was a substudy of the three-yr CENTRAL study, an RCT on safety and efficacy of early (week 7 post-engraftment) conversion from cyclosporine A (CsA) to everolimus vs. continued CsA. Thirty-nine recipients [median age 64 yr, (range 31-81)] completed echocardiographic evaluations at baseline, one, and three yr.

Results: After three yr, there was no difference between groups in left ventricle (LV) diastolic function, LV systolic function, LV morphology, and blood pressure response. We observed a relevant decrease in LV mass (CsA; 9.6%, p = 0.008, vs. everolimus; 7.0% reduction, p = 0.15), stabilized LV diastolic function, and a trend toward lower systolic blood pressure with 6 mmHg decrease in both arms (CsA, p = 0.08; everolimus, p = 0.14). Diastolic blood pressure was significantly reduced (8 mmHg decrease, p = 0.002) only in everolimus patients.

Conclusions: After three-yr follow-up, no clinically relevant effect on cardiac function of an early conversion from CsA to an everolimus-based immunosuppressive regimen was detected in de novo renal transplant recipients.

Keywords: calcineurin inhibitor; cardiovascular disease; echocardiography; everolimus; kidney transplantation.