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

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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.

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Funding

This study has been partially funded by Redes Tematicas De Investigacion Cooperativa En Salud; REDINREN (RD16/0009/0023) co-funded by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”, and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (2017-SGR-1331).

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Author notes

  1. David Cucchiari and José Ríos contributed equally to this work.

Authors and Affiliations

  1. Renal Transplant Unit, Hospital Clínic, Carrer Villaroel 170, 08023, Barcelona, Spain

    David Cucchiari, 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, Josep M. Campistol, Fritz Diekmann & Frederic Oppenheimer

  2. Medical Statistics Core Facility, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    José Ríos & Ferran Torres

  3. Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain

    José Ríos & Ferran Torres

  4. Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Ignacio Revuelta, Jordi Rovira & Fritz Diekmann

  5. Red de Investigación Renal (REDINREN), Madrid, Spain

    Ignacio Revuelta, Jordi Rovira & Fritz Diekmann

  6. Pathology Unit, Hospital Clínic, Barcelona, Spain

    Manel Solè

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  1. David Cucchiari
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Correspondence to David Cucchiari or Fritz Diekmann.

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Conflict of interest

DC has received speaker fees from Novartis and travel support from Astellas and Novartis. PVA has received travel support from Astellas, Novartis, Chiesi, Sandoz and speaker fees from Alexion and Mallinkrodt. GJP has received travel support from Sandoz. NE has received travel support from Novartis, Astellas and Chiesi. IR received speaker fees from Novartis and travel support from Sandoz, Pfizer y Astellas. FT has received DSMB fees from ImClone, Daiichi-Sankyo Pharma Development, ArQule and Rovi and speaker fees from Bayer. JMC has had consultancy agreements with Pfizer, Wyeth, Novartis and Roche; has received research funding from Pfizer and Novartis; and has been a scientific advisor or board member for Novartis and Pfizer and has received lecture fees from Alexion. JR has received DSMB fees from SOLTI and speaker fees in biostatistical education from SOLTI, Boehringer Ingelheim, Grunenthal, AMGEN and Novartis without relation of the present work. FD has received research grants and speaker fees from Astellas, Neovii, Novartis, Pfizer, Teva, Transplant Biomedicals. FO has received speaker fees from Novartis, Sanofi and Neovii and travel support from Novartis. AMJ, ENM, EDSA, FC, MS, JVT and MJR reported no conflict of interest. The results presented in this paper have not been published previously in whole or part, except in abstract format

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Cucchiari, D., Ríos, J., Molina-Andujar, A. et al. Combination of calcineurin and mTOR inhibitors in kidney transplantation: a propensity score analysis based on current clinical practice. J Nephrol 33, 601–610 (2020). https://doi.org/10.1007/s40620-019-00675-2

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