Combination of calcineurin and mTOR inhibitors in kidney transplantation: a propensity score analysis based on current clinical practice

David Cucchiari*, José Ríos, Alicia Molina-Andujar, Enrique Montagud-Marrahi, Ignacio Revuelta, Pedro Ventura-Aguiar, Gastón J. Piñeiro, Erika De Sousa-Amorim, Nuria Esforzado, Frederic Cofán, Jose Vicente Torregrosa, Jessica Ugalde-Altamirano, Maria José Ricart, Jordi Rovira, Ferran Torres, Manel Solè, Josep M. Campistol, Fritz Diekmann, Frederic Oppenheimer

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Introduction: The TRANSFORM study demonstrated that an immunosuppression based on a combination of calcineurin inhibitors and de-novo mTOR inhibitors (mTORi) is safe and effective in kidney transplant recipients. However, data that validate this approach in clinical practice are currently missing. Materials and methods: Analysis of 401 kidney transplant recipients transplanted from June 2013 to December 2016. All patients received tacrolimus with prednisone in combination with either mycophenolate (n = 186) or mTORi (either everolimus or sirolimus, n = 215). A propensity score to receive mTORi was calculated based on the inverse probability of treatment weighting (IPTW) from the following parameters: age and sex of donor and recipient, BMI, previous transplants, diabetes, cPRA, dialysis before transplantation, dialysis vintage, type of donor, ABO-incompatibility, HLA-mismatches, induction and ischemia time. Median follow-up was 2.6 [1.9; 3.7] years. Results: Cox-regression analysis suggests good results for mTORi versus MPA in terms of 1-year biopsy-proven acute rejection (BPAR, P = 0.063), 1-year graft loss (P = 0.025) and patient survival (P < 0.001). Results observed for BPAR and graft failure were largely attributed to those patients that would have been excluded by the TRANSFORM because of some exclusion criteria (52.9% of the population, P = 0.003 for 1-year BPAR and P = 0.040 for graft loss). In patients who met selection criteria for TRANSFORM, no effect of treatment for BPAR or graft failure was observed, while the beneficial effect on overall survival persisted. Conclusions: In a real-life setting, a protocol based on de-novo mTORi with tacrolimus and prednisone could be employed as a standard immunosuppressive regimen and was associated with good outcomes.

Original languageAmerican English
Pages (from-to)601-610
Number of pages10
JournalJournal of Nephrology
Volume33
Issue number3
DOIs
Publication statusPublished - 1 Jun 2020

Keywords

  • Kidney transplantation
  • mTOR inhibitors
  • Propensity score
  • Rejection
  • Survival

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