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Calcineurin and mTOR inhibitors in kidney transplantation: integrative metamodeling on transplant survival and kidney function

  • Nephrology - Original Paper
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Abstract

In our study, we examined the efficacy of mTOR (mammalian target of rapamycin) inhibitors, specifically rapamycin (Rap), compared to calcineurin inhibitors (CNIs) in kidney transplantation. By conducting a comprehensive search across reputable databases (EMBASE, Scopus, PubMed, Cochrane, and Crossref), we gathered data for a six-month post-transplantation period. Our analysis revealed that mTOR inhibitor administration resulted in improved glomerular filtration rate (GFR) and serum creatinine levels. However, it is important to note that the mTOR inhibitor group had a higher incidence of acute rejection after biopsy. Through molecular modeling, we observed that Rap exhibited a superior binding affinity for mTOR compared to CNIs’ binding to calcineurin, probably contributing to the transplant rejection. Our meta-analysis supports the cautious use of an optimal mTOR inhibitor in conjunction with careful consideration of clinical features when minimizing CNIs early in the transplantation process. This is because mTOR inhibitors have complementary mechanisms of action, a low nephrotoxicity profile, and favorable outcomes in serum creatinine and GFR, which contribute to improved transplant survival.

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Funding

This work received support from the Ministry of Science and Higher Education of the Russian Federation under goszadanie no. FSER-2021-0013. We would like to acknowledge the ITMO Fellowship and Professorship Program and Priority 2030 for their infrastructural support.

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Authors and Affiliations

  1. Faculty of Life Sciences, Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan

    Hina Khalid

  2. School of Science and Engineering, Department of Computer Science, Università degli studi di Verona, Verona, Italy

    Muhammad Mazhar Fareed

  3. Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany

    Thomas Dandekar

  4. Laboratory of Chemoinformatics, Infochemistry Scientific Center, ITMO University, Saint-Petersburg, Russian Federation

    Sergey Shityakov

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  1. Hina Khalid
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Correspondence to Hina Khalid.

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Khalid, H., Fareed, M.M., Dandekar, T. et al. Calcineurin and mTOR inhibitors in kidney transplantation: integrative metamodeling on transplant survival and kidney function. Int Urol Nephrol 56, 1403–1414 (2024). https://doi.org/10.1007/s11255-023-03754-3

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  • DOI: https://doi.org/10.1007/s11255-023-03754-3

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