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Conversion From Calcineurin to Mammalian Target of Rapamycin Inhibitors in Liver Transplantation: A Meta-Analysis of Randomized Controlled Trials.


Type

Article

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Authors

Glover, Thomas E 
Watson, Christopher JE 
Gibbs, Paul 
Bradley, J Andrew 
Ntzani, Evangelia E 

Abstract

BACKGROUND: Conversion to mammalian target of rapamycin inhibitors (mTORi) is often used in liver transplantation to overcome calcineurin inhibitor (CNI) nephrotoxicity but the evidence base for this approach is not well defined. To summarize the evidence, from randomized clinical trials (RCTs), for conversion from CNI to mTORi-based immunosuppression after liver transplantation. METHODS: Databases and conference abstracts were searched up to August 2015. The RCTs evaluating conversion from CNI to mTORi-based maintenance immunosuppression after adult liver transplantation. Descriptive and quantitative information was extracted; summary mean difference and risk ratio (RR) estimates were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and I. RESULTS: Ten RCTs, with a total of 1927 patients, met the final inclusion criteria. Patients converted to mTORi had significantly better renal function at 1 year after randomization compared with patients remaining on CNI (mean difference, 7.48 mL/min per 1.73 m; 95% confidence interval [95% CI], 3.18-11.8). The risks of graft loss (RR, 0.77; 95% CI, 0.29-2.09; I, 31%) and patient death (RR, 1.05; 95% CI, 0.63-1.73; I, 0%) were similar for patients converted to mTORi and patients remaining on CNI. However, conversion to mTORi was associated with a higher risk of acute rejection (RR, 1.76; 95% CI, 1.33-2.34; I, 0%) and study discontinuation due to adverse events (RR, 2.17; 95% CI, 1.38-3.44; I, 63%) up to 1 year after randomization. CONCLUSIONS: Conversion from CNI to mTORi after liver transplantation is associated with improved renal function after 1 year but increases the risk of acute rejection and may be poorly tolerated.

Description

Keywords

Calcineurin Inhibitors, Chi-Square Distribution, Drug Substitution, Graft Rejection, Graft Survival, Humans, Immunosuppressive Agents, Kidney, Liver Transplantation, Protein Kinase Inhibitors, Risk Assessment, Risk Factors, TOR Serine-Threonine Kinases, Time Factors, Treatment Outcome

Journal Title

Transplantation

Conference Name

Journal ISSN

0041-1337
1534-6080

Volume Title

100

Publisher

Ovid Technologies (Wolters Kluwer Health)
Sponsorship
The study was funded in part by the NIHR Cambridge Biomedical Research Centre.