Neutral impact of mTOR inhibitors on cardiovascular outcomes after kidney transplantation

Abstract Background In kidney transplantation, it remains unclear whether mTOR inhibitors (mTORi) improve cardiovascular outcomes—through plaque stabilization and attenuation of left ventricular remodeling—or worsen them by deranging glucose and lipid metabolism. We aimed to assess the true impact of this drug class on major cardiovascular outcomes in a deeply phenotyped cohort with long-term follow-up. Materials and methods All patients transplanted at our center between June 1st, 2013 and December 31st, 2019 (n = 845) were screened for inclusion. A total of 492 patients were selected through 1:1 propensity score matching (PSM) based on 18 key donor and recipient variables. All patients received tacrolimus (TAC), steroids, and either mTORi (n = 246) or mycophenolic acid (MPA) (n = 246). The primary outcome was major adverse cardiovascular events (MACE), defined as non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. Results Baseline variables were adequately balanced after PSM (absolute standardized difference < 0.10). Over a mean follow-up of 4.81 ± 2.49 years, MACE occurred in 78 patients (15.9%), with no significant difference between the mTORi and MPA groups (HR[95%CI] 0.84[0.54–1.30], P = 0.443). Subgroup analyses—including patients with diabetes, prior MACE, stable immunosuppression, or pre-transplant ischemia testing—also showed no differences. Independent predictors of MACE were age (HR[95%CI] for upper tertile 2.17[1.38–3.42], P < 0.001), dialysis vintage (HR[95%CI] for upper tertile 1.91[1.22–3.01], P = 0.005), prior myocardial infarction (HR[95%CI] 2.12[1.19–3.78], P = 0.011), and deceased versus living donor graft (HR[95%CI] 3.42[1.47–7.92], P = 0.004). Conclusions Cardiovascular disease after kidney transplantation occurs due to non-modifiable risk factors and does not appear to be related to baseline immunosuppression.