Background: Although optimization of immunosuppressive schemes in renal transplantation have minimized acute posttransplant complications, long-term outcomes are still not optimal and most of the chronic graft damage is drug-related. Therefore, to define the best long-term maintenance immunosuppressive regimen is of major importance in renal transplantation. To assess this objective, we undertook a large, multicenter cohort study in Italy. Methods: We retrospectively analyzed data of 5635 patients (enrolled from 1983 to 2012) and we assessed the impact of 3 major immunosuppressive regimens (calcineurin inhibitors+antimetabolites+corticosteroids [CNI+ANT+CS] vs CNI+mammalian target-of-rapamycin (mTOR) inhibitors+CS [CNI+mTOR-I+CS] vs CNI+CS) on long-term clinical outcomes by employing several statistical algorithms. Results: The overall difference in the incidence of outcome over time was not statistically different within the first 5 years of follow-up (P =.13); however, it became significant at 10 years and 20 years (P <.01), with the CNI+CS group showing the lowest cumulative incidence of outcome. Compared with the CNI+ANT+CS group, the CNI+mTOR-I+CS group patients had a significantly higher risk of outcome (hazard ratio [HR], 1.30; P =.024); the difference remained significant and even increased in magnitude after adjustment for potential confounders (HR, 1.38; P =.006). Similarly, patients in the CNI+CS group had a significantly higher risk of the outcome (HR, 1.64; P <.001). Conclusion: Our data highlight the fact that CNI+ANT+CS is the “gold standard” therapy in renal transplantation, but, whenever required, the introduction of mTOR-Is instead of ANT may not dramatically modify major clinical outcomes. The use of mTOR-I could be a valuable pharmacologic tool to minimize CNI complications and insure adequate immunosuppression.
|Publication status||Accepted/In press - Jan 1 2019|
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