Mammalian Target of Rapamycin Inhibitors Vs Calcineurin Inhibitors in Chronic Graft Rejection After Lung Transplantation: A Systematic Review and Meta‐Analysis

• Published in: Transplantation proceedings 2021-12, Vol.53 (10), p.3056-3064
• Main Authors: de Souza, Andressa Rodrigues, dos Santos, Thulssa Auxiliadora Gomes Medeiros, Von Jakitsch, Camila Bomfim, de Sant'Anna, Ana Lúcia Gargione Galvão, de Claudio, João Carlos Marchiori, Branco, João Nelson Rodrigues, Giovanazzi, Rosemeire Simone Dellacrode, Junior, Nelson Americo Hossne, Pimentel, Walace de Souza, da Costa, Suelen Alves Creste Martins, Girones, Puri, Machado, Regimar Carla
• Format: Article
• Language: English
• Subjects: Calcineurin Inhibitors - adverse effects; Graft Rejection - prevention & control; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Lung Transplantation - adverse effects; MTOR Inhibitors; Sirolimus; TOR Serine-Threonine Kinases
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2021.09.019

•Mammalian target of rapamycin (mTOR) inhibitors indicated a risk of death 12 months after lung transplant.•mTOR inhibitors indicated a greater trend toward the risk of acute lung rejection.•There is no significant chronic graft rejection up to 12 months of treatment.•mTOR inhibitors favor an increase in the risk of experiencing adverse events.•mTOR inhibitors recommended for patients with renal dysfunction after use of calcineurin inhibitors. The number of lung transplantations has been rising constantly. However, use of this therapeutic resource is limited by several issues that are difficult to resolve, such as chronic graft rejection and complications secondary to immunosuppression. This systematic review compared mammalian target of rapamycin (mTOR) inhibitor immunosuppression associated with low-dose calcineurin inhibitors with isolated calcineurin inhibitor immunosuppression on the new-onset chronic rejection development and mortality 12 months after lung transplantation. Three controlled randomized clinical trials (SHITRIT, NOCTET, and 4EVERLUNG) were selected from electronic databases. Meta-analysis of the data at 12 months postintervention showed that only 4EVERLUNG assessed chronic graft rejection, with a higher incidence in the control group; however, the difference was not statistically significant (P = .197). Significant data were related to an increase in the number of adverse events (P = .0064) and improved renal function (P < .0001) in the mTOR inhibitor-based scheme. The other outcomes indicated a trend toward greater risk of death and acute graft rejection with the use of mTORs. The researchers suggest considering the use of mTOR inhibitors, whose greatest benefit is felt by patients with renal dysfunction, in association with the use of calcineurin inhibitors, because of the imminent risk of death among patients with renal failure.