Use of sirolimus in liver transplant recipients with renal insufficiency: a systematic review and meta-analysis.
Sirolimus is used in patients with renal insufficiency after liver transplantation (LT) and especially in those with calcineurin inhibitor (CNI)-associated nephrotoxicity. We conducted a systematic review of all randomized controlled trials and observational studies to test the hypothesis that the use of sirolimus is associated with an improvement in renal function at 1 year in LT recipients with renal insufficiency [glomerular filtration rate (GFR) < 60 mL/minute or creatinine level ≥ 1.5 mg/dL]. We performed a search of all major databases, conference proceedings, and relevant journals through December 2009 and contacted content experts, corresponding authors, and the pharmaceutical manufacturer. A random effects model was used to determine the pooled estimate of the change in renal function and pooled risk estimates of adverse events that may be associated with sirolimus-based therapy at 1 year. Eleven studies (three randomized controlled trials and eight observational studies) met the final inclusion criteria. A nonsignificant improvement of 3.38 mL/minute [95% confidence interval (CI) = -2.93 to 9.69] was observed in methodologically sound observational studies and controlled trials reporting the primary outcome. In controlled trials, baseline GFR >50 mL/min sirolimus use was associated with an improvement of 10.35 mL/minute (95% CI = 3.98-16.77) in GFR or creatinine clearance. Sirolimus was not significantly associated with death [relative risk (RR) = 1.12, 95% CI = 0.66-1.88] or graft failure (RR = 0.80, 95% CI = 0.45-1.41), although reporting was incomplete. It was associated with a statistically significant risk of infection (RR = 2.47, 95% CI = 1.14-5.36), rash (RR = 7.57, 95% CI = 1.75-32.70), ulcers (RR = 7.44, 95% CI = 2.03-27.28), and discontinuation of therapy (RR = 3.61, 95% CI = 1.32-9.89).


CONCLUSIONS
Conversion to sirolimus from CNIs is associated with a nonsignificant improvement in renal function in LT recipients with renal insufficiency, although the results are limited by heterogeneity, a risk of bias, and a lack of standardized reporting.
Asrani
Sumeet K
SK
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Leise
Michael D
MD
West
Colin P
CP
Murad
M Hassan
MH
Pedersen
Rachel A
RA
Erwin
Patricia J
PJ
Tian
Jianmin
J
Wiesner
Russell H
RH
Kim
W Ray
WR
D000328:Adult; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016031:Liver Transplantation / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000139:chemically induced*; D020123:Sirolimus / Q000009:adverse effects*; D016896:Treatment Outcome
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus
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