Use of sirolimus in liver transplant recipients with renal insufficiency: a systematic review and meta-analysis.

Sumeet K. Asrani, Michael D. Leise, Colin P. West, M. Hassan Murad, Rachel A. Pedersen, Patricia J. Erwin, Jianmin Tian, Russell H. Wiesner, W. Ray Kim

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49 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1360-1370
Number of pages11
JournalHepatology (Baltimore, Md.)
Volume52
Issue number4
DOIs
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Hepatology

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    Asrani, S. K., Leise, M. D., West, C. P., Murad, M. H., Pedersen, R. A., Erwin, P. J., Tian, J., Wiesner, R. H., & Kim, W. R. (2010). Use of sirolimus in liver transplant recipients with renal insufficiency: a systematic review and meta-analysis. Hepatology (Baltimore, Md.), 52(4), 1360-1370. https://doi.org/10.1002/hep.23835