Outcomes of Mammalian Target of Rapamycin Inhibitor Regimens in Kidney Transplant Recipients with Pre-Transplant Primary Diagnosis of Hypertension and Other Etiologies: An Observational Study

Objective: We aimed to examine the outcomes associated with the mammalian target of rapamycin inhibitor (sirolimus or everolimus), (m-TORi) regimens in kidney transplant recipients (KTR) with primary diagnoses of hypertension.

Methods: In this retrospective observational study, 187,381 adult KTRs were classified into the hypertension or non-hypertension cohort based on their primary renal diagnosis pre-transplant. Cox regressions were used to analyze the risks for death and graft loss associated with the following regimens: m-TORi with or without steroids combined with cyclosporine (m-TORi+CSA), mycophenolate (m-TORi+MPA) or tacrolimus (m-TORi+Tac); cyclosporine with or without steroids combined with mycophenolate (CSA+MPA); and other regimens.

Results: The risk of death-with-graft-function did not differ between mTORi regimens in KTRs with a primary diagnosis of HTN [mTORi+CSA vs: mTORi+MPA (HR=0.88; 95% CI=0.68-1.14) and mTORi+Tac (HR=1.16; 95% CI=0.91-1.47); and mTORi+MPA vs. mTORi+Tac (HR=1.31; 95% CI=1.00-1.72)]. However, in KTRs with a primary diagnosis other than HTN, mTORi+CSA is associated with a lower risk of death-with-graft-function than mTORi+MPA or mTORi+Tac [mTORi+CSA vs. mTORi+MPA: HR=0.81; 95% CI=0.71-0.92] and [mTORi+CSA vs. mTORi+Tac: HR=0.76; 95% CI=0.66-0.87]. In both primary diagnosis cohorts, the risks of overall and death-censored graft loss are higher with m-TORi+MPA than the other m-TORi regimens.

Conclusion: MTORi+MPA is associated with higher risks of graft loss regardless of pre-transplant primary diagnosis. MTORi+CSA is associated with a higher likelihood of survival with a functioning graft in KTRs with a non-HTN primary diagnosis, a benefit not seen among KTRs with a primary diagnosis of HTN. Therefore, outcomes associated with mTORi regimens vary with the pre-transplant primary diagnosis classification of hypertension or non-hypertension: these associations may be considered in mTORi regimen selection after kidney transplantation.