Original Article
A Systematic Review of Conversion From Calcineurin Inhibitor to Mammalian Target of Rapamycin Inhibitors for Maintenance Immunosuppression in Kidney Transplant Recipients

https://doi.org/10.1111/ajt.12795Get rights and content
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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 m2, 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.

Key words:

Clinical research
dysfunction
immune modulation
immunosuppression
immunosuppressive regimens
kidney (allograft) function
kidney transplantation
maintenance
meta-analysis
minimization
nephrology
practice
withdrawal

Abbreviations

BPAR
biopsy-proven acute rejection
CAN
chronic allograft nephropathy
CI
confidence interval
CMV
cytomegalovirus
CNI
calcineurin inhibitor
CVD
cardiovascular disease
df
degree of freedom
DFG
death with functioning graft
IFTA
interstitial fibrosis and tubular atrophy
ITT
intention to treat
MPA
mycophenolic acid
mTORi
mammalian target of rapamycin inhibitor
NODAT
new-onset diabetes after transplantation
OT
on-treatment
RCT
randomized controlled trial
RR
risk ratio
WMD
weighted mean difference

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