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

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dc.citation.issue4
dc.citation.volume13
dc.contributor.authorFernandes-Silva, Gabriel [UNIFESP]
dc.contributor.authorde Paula, Mayara Ivani [UNIFESP]
dc.contributor.authorRangel, Erika B. [UNIFESP]
dc.coverageAbingdon
dc.date.accessioned2020-07-17T14:02:27Z
dc.date.available2020-07-17T14:02:27Z
dc.date.issued2017
dc.description.abstractIntroduction: 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.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Nephrol, Hosp Rim & Hipertensao, Sao Paulo, SP, Brazil
dc.description.affiliationHosp Israelita Albert Einstein, Inst Israelita Ensino & Pesquisa, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Nephrol, Hosp Rim & Hipertensao, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.format.extent367-385
dc.identifierhttp://dx.doi.org/10.1080/17425255.2017.1239708
dc.identifier.citationExpert Opinion On Drug Metabolism & Toxicology. Abingdon, v. 13, n. 4, p. 367-385, 2017.
dc.identifier.doi10.1080/17425255.2017.1239708
dc.identifier.issn1742-5255
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54822
dc.identifier.wosWOS:000399492600002
dc.language.isoeng
dc.publisherTaylor & Francis Ltd
dc.relation.ispartofExpert Opinion On Drug Metabolism & Toxicology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectPancreas transplanten
dc.subjectmTOR inhibitorsen
dc.subjectproteinuriaen
dc.subjecthyperglycemiaen
dc.subjectautophagyen
dc.titlemTOR inhibitors in pancreas transplant: adverse effects and drug-drug interactionsen
dc.typeinfo:eu-repo/semantics/article
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