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Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BACKGROUND: A systematic review and meta-analysis were performed to investigate the efficacy and safety of conversion from calcineurin inhibitors (CNIs) to mammalian target of rapamycin inhibitors (mTORi) in kidney transplant recipients (KTRs). METHODS: MEDLINE, EMBASE, PubMed, and Cochrane Library...

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Autores principales: Zeng, Jun, Zhong, Qiang, Feng, Xiaobing, Li, Linde, Feng, Shijian, Fan, Yu, Song, Turun, Huang, Zhongli, Wang, Xianding, Lin, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446650/
https://www.ncbi.nlm.nih.gov/pubmed/34539621
http://dx.doi.org/10.3389/fimmu.2021.663602
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author Zeng, Jun
Zhong, Qiang
Feng, Xiaobing
Li, Linde
Feng, Shijian
Fan, Yu
Song, Turun
Huang, Zhongli
Wang, Xianding
Lin, Tao
author_facet Zeng, Jun
Zhong, Qiang
Feng, Xiaobing
Li, Linde
Feng, Shijian
Fan, Yu
Song, Turun
Huang, Zhongli
Wang, Xianding
Lin, Tao
author_sort Zeng, Jun
collection PubMed
description BACKGROUND: A systematic review and meta-analysis were performed to investigate the efficacy and safety of conversion from calcineurin inhibitors (CNIs) to mammalian target of rapamycin inhibitors (mTORi) in kidney transplant recipients (KTRs). METHODS: MEDLINE, EMBASE, PubMed, and Cochrane Library were searched to identify randomized controlled trials (RCTs) that compared the continuation of CNI with conversion to mTORi therapy. RESULTS: Twenty-nine RCTs (5,747 KTRs) were included in our analysis. Meta-analysis of the glomerular filtration rate (SMD 0.20; 95%CI 0.10–0.31; P<0.01) and malignancy (RR 0.74; 95%CI 0.55–0.99; P=0.04) demonstrated a significant advantage of mTORi conversion over CNI continuation. However, the risk of acute rejection (RR 1.58; 95%CI 1.22–2.04; P<0.01), infection (RR 1.55; 95%CI 1.01–1.31; P=0.04), proteinuria (RR 1.87; 95%CI 1.34–2.59; P<0.01), leukopenia (RR 1.56; 95%CI 1.27–1.91; P<0.01), acne (RR 6.43; 95%CI 3.43–12.04; P<0.01), and mouth ulcer (RR 11.70; 95%CI 6.18–22.17; P<0.01) were higher in the mTORi group. More patients in the conversion group had to discontinue study medication (RR 2.52; 95%CI 1.75–3.63; P<0.01). There was no significant difference between the two groups with regard to death, graft loss, diabetes, chronic allograft nephropathy, and interstitial fibrosis/tubular atrophy. CONCLUSIONS: Posttransplant patients have a better graft function and lower incidence of malignancy after conversion from CNI to mTORi therapy. However, this conversion strategy may be prevented by the higher drug discontinuation rate due to mTORi-associated adverse events, such as more acute rejection, infection, proteinuria, leukopenia, acne, and mouth ulcer, indicating that conversion therapy may only be a treatment option in selected patients.
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spelling pubmed-84466502021-09-18 Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Zeng, Jun Zhong, Qiang Feng, Xiaobing Li, Linde Feng, Shijian Fan, Yu Song, Turun Huang, Zhongli Wang, Xianding Lin, Tao Front Immunol Immunology BACKGROUND: A systematic review and meta-analysis were performed to investigate the efficacy and safety of conversion from calcineurin inhibitors (CNIs) to mammalian target of rapamycin inhibitors (mTORi) in kidney transplant recipients (KTRs). METHODS: MEDLINE, EMBASE, PubMed, and Cochrane Library were searched to identify randomized controlled trials (RCTs) that compared the continuation of CNI with conversion to mTORi therapy. RESULTS: Twenty-nine RCTs (5,747 KTRs) were included in our analysis. Meta-analysis of the glomerular filtration rate (SMD 0.20; 95%CI 0.10–0.31; P<0.01) and malignancy (RR 0.74; 95%CI 0.55–0.99; P=0.04) demonstrated a significant advantage of mTORi conversion over CNI continuation. However, the risk of acute rejection (RR 1.58; 95%CI 1.22–2.04; P<0.01), infection (RR 1.55; 95%CI 1.01–1.31; P=0.04), proteinuria (RR 1.87; 95%CI 1.34–2.59; P<0.01), leukopenia (RR 1.56; 95%CI 1.27–1.91; P<0.01), acne (RR 6.43; 95%CI 3.43–12.04; P<0.01), and mouth ulcer (RR 11.70; 95%CI 6.18–22.17; P<0.01) were higher in the mTORi group. More patients in the conversion group had to discontinue study medication (RR 2.52; 95%CI 1.75–3.63; P<0.01). There was no significant difference between the two groups with regard to death, graft loss, diabetes, chronic allograft nephropathy, and interstitial fibrosis/tubular atrophy. CONCLUSIONS: Posttransplant patients have a better graft function and lower incidence of malignancy after conversion from CNI to mTORi therapy. However, this conversion strategy may be prevented by the higher drug discontinuation rate due to mTORi-associated adverse events, such as more acute rejection, infection, proteinuria, leukopenia, acne, and mouth ulcer, indicating that conversion therapy may only be a treatment option in selected patients. Frontiers Media S.A. 2021-09-03 /pmc/articles/PMC8446650/ /pubmed/34539621 http://dx.doi.org/10.3389/fimmu.2021.663602 Text en Copyright © 2021 Zeng, Zhong, Feng, Li, Feng, Fan, Song, Huang, Wang and Lin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zeng, Jun
Zhong, Qiang
Feng, Xiaobing
Li, Linde
Feng, Shijian
Fan, Yu
Song, Turun
Huang, Zhongli
Wang, Xianding
Lin, Tao
Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
title Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
title_full Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
title_fullStr Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
title_full_unstemmed Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
title_short Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
title_sort conversion from calcineurin inhibitors to mammalian target of rapamycin inhibitors in kidney transplant recipients: a systematic review and meta-analysis of randomized controlled trials
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446650/
https://www.ncbi.nlm.nih.gov/pubmed/34539621
http://dx.doi.org/10.3389/fimmu.2021.663602
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