Impact of 3 Major Maintenance Immunosuppressive Protocols on Long-term Clinical Outcomes: Result of a Large Multicenter Italian Cohort Study Including 5635 Renal Transplant Recipients

C. Caletti, P. M. Ferraro, A. Corvo, G. Tessari, S. Sandrini, I. Capelli, E. Minetti, L. Gesualdo, G. Girolomoni, L. Boschiero, A. Lupo, G. Zaza

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Abstract

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.

Original languageEnglish
JournalTransplantation Proceedings
DOIs
Publication statusAccepted/In press - Jan 1 2019

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ASJC Scopus subject areas

  • Surgery
  • Transplantation

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