Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão

Bibliographic Details
Main Author: Souza, Andressa Rodrigues de
Publication Date: 2019
Format: Doctoral thesis
Language: por
Source: Repositório Institucional da UFSCAR
Download full: https://repositorio.ufscar.br/handle/ufscar/11612
Summary: The growth of lung transplantation has been constant throughout the world, and with this, the results presented have been progressively better, both in the short and long term. Despite this reality, some problems of difficult solution limit these programs, such as chronic graft rejection and complications secondary to long-term immunosuppression. The immunosuppressive strategies used in lung transplantation are based on triple schemes, composed of a calcineurin inhibitor, an antimetabolic agent and corticosteroids. A fourth group of immunosuppressants consists of inhibitors of cell proliferation, in particular, mTOR inhibitors. In this sense, this review aimed to compare the immunosuppressive regimen based on a calcineurin inhibitor-associated mTOR inhibitor at reduced dose with the calcineurin inhibitor alone in the chronic rejection of the posttransplant lung graft. In order to do so, we applied the methodological design of systematic review of the literature, through searches in electronic health databases (MEDLINE, Wef of Science, Scopus, Cochrane Central, EMBASE and LILACS) and in secondary manual resources. Six scientific articles composed the corpus of analysis for the qualitative synthesis of the results, which referred to three studies named SHITRIT, NOCTET and 4EVERLUNG. The main outcomes were the safety of substitution therapy for calcineurin inhibitor-based immunosuppressive therapy by the treatment of mTOR inhibitor with low patient mortality as well as maintaining efficacy in controlling events of chronic graft rejection. The relevance of the data that indicated an improvement in the renal function of the patients when submitted to the therapy with inhibitor mTOR in relation to calcineurin inhibitors was unanimously highlighted. The studies present a high reliability index due to the manifestation of low risk of bias in most of the items evaluated for the assertive conduction of a randomized clinical trial, in addition to presenting an important recommendation force for clinical decision making. In this sense, this systematic review guides a weighting in the use of mTOR inhibitors, considering the greater risk of mortality in the first year of treatment associated with this therapy. For patients with renal dysfunction associated with the isolated use of calcineurin inhibitors, this review "recommends" a change in the therapeutic regimen for the insertion of mTOR inhibitors into calcineurin inhibitors at a reduced dose, considering the imminent risk of mortality of lung transplant patients under renal insufficiency.
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spelling Souza, Andressa Rodrigues deMachado, Regimar Carlahttp://lattes.cnpq.br/1310723429860987http://lattes.cnpq.br/28652842564891822019-08-05T19:52:50Z2019-08-05T19:52:50Z2019-04-24SOUZA, Andressa Rodrigues de. Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão. 2019. Tese (Doutorado em Enfermagem) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11612.https://repositorio.ufscar.br/handle/ufscar/11612The growth of lung transplantation has been constant throughout the world, and with this, the results presented have been progressively better, both in the short and long term. Despite this reality, some problems of difficult solution limit these programs, such as chronic graft rejection and complications secondary to long-term immunosuppression. The immunosuppressive strategies used in lung transplantation are based on triple schemes, composed of a calcineurin inhibitor, an antimetabolic agent and corticosteroids. A fourth group of immunosuppressants consists of inhibitors of cell proliferation, in particular, mTOR inhibitors. In this sense, this review aimed to compare the immunosuppressive regimen based on a calcineurin inhibitor-associated mTOR inhibitor at reduced dose with the calcineurin inhibitor alone in the chronic rejection of the posttransplant lung graft. In order to do so, we applied the methodological design of systematic review of the literature, through searches in electronic health databases (MEDLINE, Wef of Science, Scopus, Cochrane Central, EMBASE and LILACS) and in secondary manual resources. Six scientific articles composed the corpus of analysis for the qualitative synthesis of the results, which referred to three studies named SHITRIT, NOCTET and 4EVERLUNG. The main outcomes were the safety of substitution therapy for calcineurin inhibitor-based immunosuppressive therapy by the treatment of mTOR inhibitor with low patient mortality as well as maintaining efficacy in controlling events of chronic graft rejection. The relevance of the data that indicated an improvement in the renal function of the patients when submitted to the therapy with inhibitor mTOR in relation to calcineurin inhibitors was unanimously highlighted. The studies present a high reliability index due to the manifestation of low risk of bias in most of the items evaluated for the assertive conduction of a randomized clinical trial, in addition to presenting an important recommendation force for clinical decision making. In this sense, this systematic review guides a weighting in the use of mTOR inhibitors, considering the greater risk of mortality in the first year of treatment associated with this therapy. For patients with renal dysfunction associated with the isolated use of calcineurin inhibitors, this review "recommends" a change in the therapeutic regimen for the insertion of mTOR inhibitors into calcineurin inhibitors at a reduced dose, considering the imminent risk of mortality of lung transplant patients under renal insufficiency.O crescimento do número de transplantes de pulmão tem sido constante no mundo todo, e, com isso, os resultados apresentados têm sido progressivamente melhores, tanto em curto e em longo prazo. Apesar desta realidade, alguns problemas de difícil solução limitam estes programas, como a rejeição crônica do enxerto e as complicações secundárias à imunossupressão de longa duração. As estratégias imunossupressoras utilizadas no transplante de pulmão baseiam-se em esquemas triplos, compostos de um inibidor de calcineurina, um antimetabólico e corticosteroides. Um quarto grupo de imunossupressores constitui-se de inibidores da proliferação celular, em particular, os inibidores de mTOR. Nesse sentido, esta revisão se propôs a comparar o esquema de imunossupressão baseado em inibidor de mTOR associado a inibidor de calcineurina em dose reduzida com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-tranplante de pulmão. Para tanto, aplicou-se o desenho metodológico de revisão sistemática da literatura, por meio de buscas em bases eletrônicas da saúde (MEDLINE, Wef of Science, Scopus, Cochrane Central, EMBASE e LILACS) e em recursos manuais secundários. Seis artigos científicos compuseram o corpus de análise para a síntese qualitativa dos resultados, os quais se referiam a três estudos nominados SHITRIT, NOCTET e 4EVERLUNG. Os desfechos principais apontaram para a segurança da terapêutica de substituição do tratamento imunossupressor baseado em inibidor de calcineurina pelo tratamento baseado em inibidor de mTOR, com baixo índice de mortalidade dos pacientes, assim como da manutenção da eficácia em controlar eventos de rejeição crônica do enxerto. Destacou-se de forma unânime, a relevância dos dados que apontaram melhora na função renal dos pacientes quando submetidos à terapêutica com inibidor mTOR em relação a inibidores de calcineurina. Os estudos apresentam alto índice de confiabilidade pela manifestação de baixo risco de viés na maioria dos itens avaliados para a condução assertiva de um ensaio clínico randomizado, além de apresentarem importante força de recomendação para a tomada de decisão clínica. Nesse sentido, esta revisão sistemática orienta para um ponderamento na utilização de inibidores mTOR, considerando o maior risco de mortalidade do paciente no primeiro ano de tratamento associado a essa terapêutica. Para pacientes que apresentem disfunção renal associada ao uso isolado de inibidores de calcineurina, esta revisão “recomenda” a troca de regime terapêutico para a inserção de inibidores mTOR aos inibidores de calcineurina em dose reduzida, considerando o risco iminente de mortalidade dos pacientes transplantados de pulmão sob insuficiência renal.Não recebi financiamentoporUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Enfermagem - PPGEnfUFSCarTransplante de pulmãoRejeição crônica do enxertoImunossupressoresLung transplantationChronic graft rejectionImmunosuppressantsCIENCIAS DA SAUDE::ENFERMAGEM::ENFERMAGEM MEDICO-CIRURGICAComparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmãoComparison of the immunosuppressive scheme using mTOR associated with the calcineurin inhibitor with the calcineurin inhibitor isolated in the chronic rejection of the post-transplant lung graftinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisOnlineinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALTESE - Andressa Rodrigues de Souza.pdfTESE - Andressa Rodrigues de Souza.pdfTese de doutorado Andressa Rodrigues de Souzaapplication/pdf2137800https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/11612/1/TESE%20-%20Andressa%20Rodrigues%20de%20Souza.pdf2f56768d9d26fd505b13ce4329f8ca15MD51LICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão
dc.title.alternative.eng.fl_str_mv Comparison of the immunosuppressive scheme using mTOR associated with the calcineurin inhibitor with the calcineurin inhibitor isolated in the chronic rejection of the post-transplant lung graft
title Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão
spellingShingle Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão
Souza, Andressa Rodrigues de
Transplante de pulmão
Rejeição crônica do enxerto
Imunossupressores
Lung transplantation
Chronic graft rejection
Immunosuppressants
CIENCIAS DA SAUDE::ENFERMAGEM::ENFERMAGEM MEDICO-CIRURGICA
title_short Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão
title_full Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão
title_fullStr Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão
title_full_unstemmed Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão
title_sort Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão
author Souza, Andressa Rodrigues de
author_facet Souza, Andressa Rodrigues de
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/2865284256489182
dc.contributor.author.fl_str_mv Souza, Andressa Rodrigues de
dc.contributor.advisor1.fl_str_mv Machado, Regimar Carla
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1310723429860987
contributor_str_mv Machado, Regimar Carla
dc.subject.por.fl_str_mv Transplante de pulmão
Rejeição crônica do enxerto
Imunossupressores
topic Transplante de pulmão
Rejeição crônica do enxerto
Imunossupressores
Lung transplantation
Chronic graft rejection
Immunosuppressants
CIENCIAS DA SAUDE::ENFERMAGEM::ENFERMAGEM MEDICO-CIRURGICA
dc.subject.eng.fl_str_mv Lung transplantation
Chronic graft rejection
Immunosuppressants
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::ENFERMAGEM::ENFERMAGEM MEDICO-CIRURGICA
description The growth of lung transplantation has been constant throughout the world, and with this, the results presented have been progressively better, both in the short and long term. Despite this reality, some problems of difficult solution limit these programs, such as chronic graft rejection and complications secondary to long-term immunosuppression. The immunosuppressive strategies used in lung transplantation are based on triple schemes, composed of a calcineurin inhibitor, an antimetabolic agent and corticosteroids. A fourth group of immunosuppressants consists of inhibitors of cell proliferation, in particular, mTOR inhibitors. In this sense, this review aimed to compare the immunosuppressive regimen based on a calcineurin inhibitor-associated mTOR inhibitor at reduced dose with the calcineurin inhibitor alone in the chronic rejection of the posttransplant lung graft. In order to do so, we applied the methodological design of systematic review of the literature, through searches in electronic health databases (MEDLINE, Wef of Science, Scopus, Cochrane Central, EMBASE and LILACS) and in secondary manual resources. Six scientific articles composed the corpus of analysis for the qualitative synthesis of the results, which referred to three studies named SHITRIT, NOCTET and 4EVERLUNG. The main outcomes were the safety of substitution therapy for calcineurin inhibitor-based immunosuppressive therapy by the treatment of mTOR inhibitor with low patient mortality as well as maintaining efficacy in controlling events of chronic graft rejection. The relevance of the data that indicated an improvement in the renal function of the patients when submitted to the therapy with inhibitor mTOR in relation to calcineurin inhibitors was unanimously highlighted. The studies present a high reliability index due to the manifestation of low risk of bias in most of the items evaluated for the assertive conduction of a randomized clinical trial, in addition to presenting an important recommendation force for clinical decision making. In this sense, this systematic review guides a weighting in the use of mTOR inhibitors, considering the greater risk of mortality in the first year of treatment associated with this therapy. For patients with renal dysfunction associated with the isolated use of calcineurin inhibitors, this review "recommends" a change in the therapeutic regimen for the insertion of mTOR inhibitors into calcineurin inhibitors at a reduced dose, considering the imminent risk of mortality of lung transplant patients under renal insufficiency.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-08-05T19:52:50Z
dc.date.available.fl_str_mv 2019-08-05T19:52:50Z
dc.date.issued.fl_str_mv 2019-04-24
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dc.identifier.citation.fl_str_mv SOUZA, Andressa Rodrigues de. Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão. 2019. Tese (Doutorado em Enfermagem) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11612.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/11612
identifier_str_mv SOUZA, Andressa Rodrigues de. Comparação do esquema de imunossupressão utilizando o mTOR associado ao inibidor de calcineurina com o inibidor de calcineurina isolado na rejeição crônica do enxerto pós-transplante de pulmão. 2019. Tese (Doutorado em Enfermagem) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11612.
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Câmpus São Carlos
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