Impact of mTOR Inhibitor Conversion Protocol on Renal Function in Cardiac Transplant Recipients

Abstract

<h3>Purpose</h3> Renal insufficiency is common in heart transplant recipients and is associated with increased all-cause cardiovascular mortality. The use of mammalian target of rapamycin inhibitor (mTORi)-based immunosuppression may help mitigate the renal insufficiency associated with calcineurin inhibitors (CI), however complete CI withdrawal is associated with an increased risk of rejection. This study aims to evaluate the effect of mTORi-based immunosuppression with low dose tacrolimus on renal function in patients post-cardiac transplant. <h3>Methods</h3> This was a single-center retrospective study of adult heart transplant recipients who were initiated on an mTORi at least six months post-transplant. The primary outcome of this study was change in renal function from pre-conversion to 3-, 6-, and 12-months post-mTORi initiation. Patients served as their own controls from pre-to-post conversion. <h3>Results</h3> A total of 61 heart transplant patients met inclusion criteria. At baseline, all patients remained on concomitant tacrolimus which was continued in 84% of patients at one year. Renal function for all patients was significantly improved at 3 months (p = 0.001) and 6 months (p = 0.004) post conversion, although the largest impact was seen in those with a baseline eGFR < 35mL/min/1.73m2. Change in renal function over time also differed by goal tacrolimus level. For patients with FK level less than 4 ng/mL, there was a significant main effect of time on eGFR (p=0.0004). There were no significant differences in renal function for the goal tacrolimus ranges of 4-6 ng/mL or 6-8 ng/mL at any time point. There were no identified safety concerns and no difference in rejection. <h3>Conclusion</h3> Overall, conversion to mTORi-based immunosuppression with low dose CI was shown to be associated with improved renal function at 3- and 6-months post conversion. Renal recovery appeared to be greatest for patients with baseline eGFR <35 mL/min/1.73m2 and in those with an FK goal < 4 ng/mL. To our knowledge, this is one of the first studies to describe the impact of FK goal levels on renal function post-conversion to mTORi-based immunosuppression. These results suggest renal improvement may be feasible while maintaining low target levels of CI therapy.