mTOR inhibitors in pancreas transplant: adverse effects and drug-drug interactions

mTOR inhibitors in pancreas transplant: adverse effects and drug-drug interactions

Author Fernandes-Silva, Gabriel Autor UNIFESP Google Scholar
de Paula, Mayara Ivani Autor UNIFESP Google Scholar
Rangel, Erika B. Autor UNIFESP Google Scholar
Abstract Introduction: Patient and pancreas allograft survival improved following reductions in surgical complications, tighter donor selection and optimization in immunosuppressive protocols. However, long-term survival of pancreas allografts is adversely affected by rejection and immunosuppressive regimen toxicity.Areas covered: This article reviews the existing literature and knowledge of mammalian target of rapamycin inhibitors (mTORi). Some clinically relevant drug-drug interactions are highlighted. We summarize the nephrotoxic and diabetogenic mechanisms of mTORi after pancreas transplant, the alternatives to minimize these effects, and report on other adverse events.Expert opinion: Calcineurin inhibitor (CNI)-based regimens remain the mainstay treatment after pancreas-kidney transplant. However, long-term use of CNIs may be associated with nephrotoxicity. Switching from CNIs to mTORi (sirolimus/SRL and everolimus/EVR) may preserve kidney function, mainly EVR conversion. However, mTORi promote an imbalance of mTOR signaling during long-term follow-up and may ultimately contribute to proteinuria and hyperglycemia. These drugs disrupt autophagy, inhibit cell proliferation, and downregulate VEGF. Therefore, it is important to comprehend and interpret the experimental data. It is equally important to critically analyze clinical studies. Of importance, minimization of side effects, based on safe approaches, can prolong kidney allograft survival. Additional randomized-controlled studies are required to assess the impact of mTORi on pancreas allograft survival.
Keywords Pancreas transplant
mTOR inhibitors
proteinuria
hyperglycemia
autophagy
xmlui.dri2xhtml.METS-1.0.item-coverage Abingdon
Language English
Date 2017
Published in Expert Opinion On Drug Metabolism & Toxicology. Abingdon, v. 13, n. 4, p. 367-385, 2017.
ISSN 1742-5255 (Sherpa/Romeo, impact factor)
Publisher Taylor & Francis Ltd
Extent 367-385
Origin http://dx.doi.org/10.1080/17425255.2017.1239708
Access rights Closed access
Type Article
Web of Science ID WOS:000399492600002
URI https://repositorio.unifesp.br/handle/11600/54822

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