Neutral impact of mTOR inhibitors on cardiovascular outcomes after kidney transplantation.

BACKGROUND

In kidney transplantation, it remains unclear whether mammalian target of rapamycin 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 1st June 2013 and 31st December 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 vs. 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.