Calcineurin inhibitor sparing with mycophenolate in kidney transplantation: a systematic review and meta-analysis.
BACKGROUND
Limiting the exposure of kidney transplant recipients to calcineurin inhibitors (CNIs) has potential merit, but there is no clear consensus on the utility of current strategies. In an attempt to aid clarification, we conducted a systematic review and meta-analysis of randomized trials that assessed CNI sparing (minimization or elimination) with mycophenolate as sole adjunctive immunosuppression.


METHODS
The search strategy identified trials where CNI sparing was accompanied by the continuation of, or conversion to, mycophenolate and compared with standard or higher dose CNI therapy. Two investigators independently examined each trial for eligibility, quality, and outcome measures. Additional subgroup analyses were assessed: (1) de novo CNI sparing; (2) elective CNI sparing beyond 2 months posttransplantation; and (3) CNI sparing for transplant dysfunction.


RESULTS
Nineteen randomized controlled trials met the inclusion criteria permitting analysis of 3312 renal transplant recipients with median follow-up of 12 months. CNI sparing significantly improved glomerular filtration rate (weighted mean difference 4.4 mL/min, 95% confidence interval [CI] 2.9-5.9, P<0.001); with some evidence, albeit weak, of improved graft survival (odds ratio 0.72, 95% CI 0.52-1.01, P=0.06). Acute rejection rates were only increased after elective CNI elimination (odds ratio 2.23, 95% CI 1.57-3.17, P<0.001). There were no significant differences in mortality, malignancy or incidence of infections.


CONCLUSIONS
CNI sparing strategies with adjunctive mycophenolate may play an important role in kidney transplant recipients. Improvements in short-term graft function, and possibly graft survival, are achievable. Longer term studies are needed to substantiate the short-term benefits, and refining elective CNI elimination protocols may help to reduce the risk of rejection.
Moore
Jason
J
Department of Nephrology and Kidney Transplantation, Renal Institute of Birmingham, University Hospital Birmingham, Edgbaston, Birmingham, United Kingdom. j.moore.3@bham.ac.uk
Middleton
Lee
L
Cockwell
Paul
P
Adu
Dwomoa
D
Ball
Simon
S
Little
Mark A
MA
Ready
Andrew
A
Wheatley
Keith
K
Borrows
Richard
R
D065095:Calcineurin Inhibitors; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000592:standards / Q000706:statistics & numerical data; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid