Conversion from calcineurin to mammalian target of rapamycin inhibitors in liver transplantation: a meta-analysis of randomised controlled trials
Glover, Thomas E
Ntzani, Evangelia E
Lippincott Williams & Wilkins
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Glover, T. E., Watson, C., Gibbs, P., Bradley, J., Ntzani, E. E., & Kosmoliaptsis, V. (2015). Conversion from calcineurin to mammalian target of rapamycin inhibitors in liver transplantation: a meta-analysis of randomised controlled trials. Transplantation, 100 621-629. https://doi.org/10.1097/TP.0000000000001006
Context: Conversion to mammalian target of rapamycin inhibitors (mTORi) is often utilised in liver transplantation to overcome calcineurin inhibitor (CNI) nephrotoxicity but the evidence base for this approach is not well defined. Objective: To summarise the evidence, from randomised-clinical-trials (RCTs), for conversion from CNI to mTORi-based immunosuppression after liver transplantation. Data Sources: Databases and conference abstracts were searched up to August 2015. Study Selection: RCTs evaluating conversion from CNI to mTORi-based maintenance immunosuppression following adult liver transplantation. Data Extraction: Descriptive and quantitative information was extracted; summary mean difference (MD) and risk ratio (RR) estimates were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and I2 . Data synthesis: Ten RCTs, with a total of 1,927 patients, met the final inclusion criteria. Patients converted to mTORi had significantly better renal function at 1 year following randomisation compared to patients remaining on CNI (MD: 7.48 mL/min/1.73m², 95%CI: 3.18-11.8). The risks of graft loss (RR: 0.77, 95%CI: 0.29-2.09, I²: 31%) and patient death (RR: 1.05, 95%CI: 0.63-1.73, I²: 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, I²: 0%) and study discontinuation due to adverse events (RR: 2.17, 95%CI: 1.38-3.44, I²: 63%) up to one year post-randomisation. Conclusions: Conversion from CNI to mTORi following liver transplantation is associated with improved renal function after one year but increases the risk of acute rejection and may be poorly tolerated.
The study was funded in part by the NIHR Cambridge Biomedical Research Centre.
External DOI: https://doi.org/10.1097/TP.0000000000001006
This record's URL: https://www.repository.cam.ac.uk/handle/1810/251136