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Lim W.H.,Sir Charles Gairdner Hospital | Lim W.H.,University of Western Australia | Eris J.,Renal Unit | Kanellis J.,Monash Medical Center | And 4 more authors.
American Journal of Transplantation | Year: 2014

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.


Lim W.H.,Sir Charles Gairdner Hospital | Lim W.H.,University of Adelaide | Chadban S.J.,University of Adelaide | Chadban S.J.,Renal Unit | And 5 more authors.
Nephrology | Year: 2010

Aim: The use of interleukin-2 receptor antibody (IL-2Ra) induction has been associated with reduced rejection rates in renal transplant recipients. However, the effect of IL-2Ra induction on graft and patient outcomes in renal transplant recipients with differing immunological risk remains unclear. Methods: Using Australia and New Zealand Dialysis and Transplant Registry, renal transplant recipients in Australia between 1995 and 2005 were included. Recipients were stratified into low immunological risk (primary grafts with ≤2 human leucocyte antigen (HLA)-mismatches and panel-reactive antibody (PRA) < 10%) or intermediate immunological risk (subsequent grafts or >2 HLA-mismatches or PRA > 25%) recipients. Recipients receiving T-cell depletive induction therapy or steroid and/or calcineurin-free inhibitor regimens were excluded. Outcomes analysed included the presence of rejection at 6 months, estimated glomerular filtration rate at 1 and 5 years, graft and patient survival. Results: 218 of 1220 (18%) low-risk and 883 of 3204 (28%) intermediate-risk recipients received IL-2Ra. In intermediate-risk recipients, IL-2Ra induction was associated with a 26% reduction in the incidence of acute rejection; but this benefit was restricted only to recipients initiated on cyclosporine-based immunosuppressive regimens. In contrast, the use of IL-2Ra in low-risk recipients was not associated with reduced rejection risk. There was no association between IL-2Ra induction and other graft or patient outcomes in both low- and intermediate-risk recipients. Conclusion: This registry analysis suggests that IL-2Ra induction may be associated with a reduction in rejection risk in cyclosporine-treated intermediate immunological risk recipients, but not in low-risk renal transplant recipients. © 2010 Asian Pacific Society of Nephrology.

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