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Title: | A systematic review of conversion from calcineurin inhibitor to mammalian target of rapamycin inhibitors for maintenance immunosuppression in kidney transplant recipients. | Authors: | Witcombe D.;Eris J.;Kanellis J.;Pussell B.;Wiid Z.;Russ G.R.;Lim W.H. | Institution: | (Lim) Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia (Lim) School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (Eris) Renal Unit, Royal Prince Alfred Hospital, Sydney, Australia (Kanellis) Department of Renal Medicine, Monash Medical Centre, Melbourne, Australia (Pussell) Department of Nephrology, Prince of Wales Hospital, Sydney, Australia (Wiid, Witcombe) Pfizer, Sydney, Australia (Russ) Nephrology and Transplantation Services, Royal Adelaide Hospital, Adelaide, Australia | Issue Date: | 31-Aug-2014 | Copyright year: | 2014 | Publisher: | Blackwell Publishing Ltd (E-mail: customerservices@oxonblackwellpublishing.com) | Place of publication: | United Kingdom | Publication information: | American Journal of Transplantation. 14 (9) (pp 2106-2119), 2014. Date of Publication: September 2014. | Journal: | American Journal of Transplantation | Abstract: | This was a systematic review of randomized controlled trials comparing delayed conversion of mammalian target of rapamycin inhibitors (mTORi) for calcineurin inhibitors (CNIs) versus CNI continuation in kidney transplantation. Databases (2000-2012) and conference abstracts (2009-2012) were searched giving a total of 29 trials. Outcomes analyzed included GFR, graft loss, rejection and adverse events and were expressed as weighted mean differences (WMDs) or as risk ratios (RRs). Patients converted to mTORi up to 1 year posttransplant in intention-to-treat analysis had higher GFR compared with those remaining on CNI (WMD 0.28 mL/min/1.73 m2, 95% confidence interval [CI] 0.21-0.36; I2 = 68%, p < 0.001). Stratifying trials by time posttransplant or type of mTORi did not change the overall heterogeneity. For on-treatment population, mTORi was associated with higher GFR (14.21 mL/min/1.73 m 2, 10.34-18.08; I2 = 0%, p = 0.970) 2-5 years posttransplant. The risk of rejection at 1 year was higher in mTORi trials (RR 1.72, 1.34-2.22; I2 = 12%, p = 0.330). Discontinuation secondary to adverse events was more common in patients on mTORi, whereas the incidence of skin cancers and cytomegalovirus infection was lower in patients on mTORi. Conversion from CNI to mTORi is associated with short-term improvements in GFR in a number of studies but longer-term follow-up data of graft and patient survival are required. This systematic review shows that conversion from calcineurin inhibitor to mammalian target of rapamycin inhibitor after kidney transplantation is associated with short-term improvement in graft function despite a higher risk of early rejection. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1111/ajt.12795 | Link to associated publication: | Click here for full text options | PubMed URL: | 25088685 [http://www.ncbi.nlm.nih.gov/pubmed/?term=25088685] | ISSN: | 1600-6135 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/41726 | Type: | Review | Subjects: | kidney graft rejection/dt [Drug Therapy] kidney transplantation meta analysis intention to treat analysis *kidney graft rejection/co [Complication] *kidney graft rejection/dt [Drug Therapy] *kidney graft rejection/pc [Prevention] rapamycin/dt [Drug Therapy] clinical trial cytomegalovirus infection glomerulus filtration rate graft recipient graft survival human immunosuppressive treatment *kidney graft outcome assessment priority journal review skin cancer systematic review *calcineurin inhibitor/ct [Clinical Trial] *calcineurin inhibitor/dt [Drug Therapy] everolimus/ct [Clinical Trial] everolimus/dt [Drug Therapy] *mammalian target of rapamycin inhibitor/ct [Clinical Trial] *mammalian target of rapamycin inhibitor/dt [Drug Therapy] rapamycin/ct [Clinical Trial] systematic review clinical trial cytomegalovirus infection glomerulus filtration rate graft recipient graft survival human immunosuppressive treatment intention to treat analysis *kidney graft *kidney graft rejection / *complication / *drug therapy / *prevention kidney graft rejection / drug therapy kidney transplantation meta analysis outcome assessment priority journal review skin cancer |
Type of Clinical Study or Trial: | Systematic review and/or meta-analysis |
Appears in Collections: | Articles |
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