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).
CONCLUSION: 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.