Treatment With mTOR Inhibitors as Primary Immunosuppression After Combined Heart and Kidney Transplantation.

Abstract

Aims: Sirolimus (SRL) mitigates cardiac allograft vasculopathy (CAV) progression and confers renal protection after heart transplantation (HT). However, its safety and efficacy in patients undergoing combined heart and kidney transplantation (HKT) are unclear. This study aimed to investigate the impact of conversion from calcineurin inhibitors (CNI) to SRL on CAV progression, renal function, and outcomes in HKT compared to isolated HT.

Methods and results: A cohort of 302 patients who underwent either HT only (n=262) or HKT (n=40) was analyzed. CAV progression was assessed by measuring the delta (Δ) annual change in plaque volume (PV) and plaque index (PI) using coronary intravenous ultrasound (IVUS). Clinical adverse outcomes included all-cause death and CAV-associated events. Overall, 217 (72%) patients were converted from CNI to SRL as primary immunosuppression. HT recipients were more likely to be converted to SRL than HKT recipients (74% vs. 55%, P=0.01). HKT was associated with higher ΔPV (P=0.01) and a trend toward higher ΔPI (P=0.06) than HT-only, but this association was attenuated after adjustment to SRL conversion. HKT was associated with similar risk of death (HR 0.98, 95%CI: 0.39-2.5, P=0.97) and CAV-related events (HR 1.6, 95%CI: 0.91-2.8, P=0.10). Conversion to SRL was associated with decreased risk of death and CAV-related events in the overall cohort. This association was not modified by the type of organ transplantation and without a significant effect on estimated glomerular filtration rate or proteinuria.

Conclusion: Conversion to sirolimus as a primary immunosuppressant could be effective for either HT-only or HKT recipients.