Impact of tacrolimus versus cyclosporin A on renal function during the first year after heart transplant

Abstract

Aims Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low-dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function. Methods and results From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy-proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7-96.4] mL/min/1.73 m 2 in TAC vs. 65.6 [57.9-83.0] mL/min/1.73 m 2 for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P < 0.001) between the two groups. Within the first year after HTx, 23 (59%) in the TAC group switched mycophenolate mofetil to everolimus, whereas 16 (48%) in the CsA group (P = 0.52). At 12 months, the rates of mortality and end-stage renal disease requiring renal replacement therapies were both 0%. In the instrumental variable analysis, no differences in renal function as well as graft rejection for 1 year after HTx existed between the TAC and CsA groups. These results were similar when taking into account of everolimus use. Conclusions Irrespective of everolimus use with low-dose CNIs, our analysis using the instrumental variable method showed no differences in renal function as well as graft rejection during the first year after HTx between HTx recipients who received TAC or CsA.

Effect of renal function under left ventricular assist device support on the cardiac function and clinical events after heart transplantation

“…1 After HTx, immunosuppressants are required to prevent graft rejection, and calcineurin inhibitors (CNIs), which are nephrotoxic, may cause irreversible renal dysfunction. 2,3 Drug-induced renal dysfunction caused by other drugs, such as antiviral and antifungal drugs, and the contrast medium used in graft evaluation might have some detrimental effects on renal function in the early and chronic periods after HTx. 4 Therefore, renal function is one of the factors closely related to the entire course of HTx.…”