Outcomes Following De Novo CNI-Free Immunosuppression After Heart Transplantation: A Single-Center Experience

Abstract

Renal impairment at the time of heart transplantation complicates the choice of subsequent immunosuppressive therapy. Calcineurin (CNI)-free regimens utilizing proliferation signal inhibitors (PSI) may mitigate against nephrotoxicity in this group; however, their effectiveness remains unclear.We present our 7-year experience with de novo CNIfree, PSI-based immunosuppression after heart transplantation. Of the 152 patients transplanted between July 1999 and July 2006, de novo immunosuppression regimens were 49 CNI-free, PSI-based, 88 CNI, 15 combination of CNI+PSI.Pretransplant creatinine clearance improved within 6 months in the PSI group (0.69 ± 0.34 mL/s vs. 1.00 ± 0.54 mL/s, p < 0.05) but not the CNI (1.32 ± 0.54 mL/s vs. 1.36 ± 0.53 mL/s, p = ns) or CNI+PSI (1.20 ± 0.24 mL/s vs. 1.20 ± 0.41 mL/s, p = ns) groups. The PSI group had more episodes of early (≤6 months) acute rejection, bacterial or fungal infections and pleural effusions but less CMV infection (p < 0.05 for all comparisons). Early CNI addition occurred in 37% of the PSI group for acute rejection. 33% of the entire cohort changed immunosuppression regimens over 3.6 ± 2.2 years follow-up.De novo CNI-free, PSI-based immunosuppression in patients with significant renal dysfunction allowed significant posttransplantation renal recovery but with increased early acute rejection, bacterial and fungal infections and pleural effusions.

Sirolimus use and incidence of venous thromboembolism in cardiac transplant recipients

“…In September 1999, sirolimus was approved by the FDA for use in renal transplant recipients. In cardiac transplant recipients, sirolimus has been used to stabilize or improve renal function in patients with calcineurin inhibitor induced nephropathy (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) and to improve or attenuate the progression of CAV (22)(23)(24)(25)(26)(27).…”

Indications, tolerance and complications of a sirolimus and calcineurin inhibitor immunosuppression regimen: Intermediate experience in pediatric heart transplantation recipients

“…Leet et al. (13) reported outcomes of de novo CNI‐free immunosuppression after Htx in adults, and Cr clearance was significantly lower in the study group. They also reported serious side effects including increased early rejection, infections and pleural effusions.…”

“…Other adult studies have reported a beneficial effect of SRL in delaying progression of TCAD (11, 12). Unfortunately, the use of SRL without adjunct CNIs in adult Htx recipients has been shown to lead to an increased incidence of early rejection and infection when compared to CNI‐based regimens and has not been reported in pediatric heart recipients for primary immunosuppression (13).…”

Kidney Disease in Liver, Cardiac, Lung, and Hematopoietic Cell Transplantation

“…Indeed, one recent report warned of high rates of rejection after patients were switched to a corticosteroid plus MMF protocol. 29 Another pilot study showed concerning outcomes with a de novo CNI-free protocol, 30 which cannot at present be recommended.…”