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

Abstract

UNLABELLED:

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.

• Authors: 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
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 52 Issue 4 Pg. 1360-70 (Oct 2010) ISSN: 1527-3350 [Electronic] United States
• PMID: 20815021 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Review, Systematic Review)

Chemical References

• Calcineurin Inhibitors
• Immunosuppressive Agents
• Creatinine
• Sirolimus

Topics

• Adult
• Calcineurin Inhibitors
• Creatinine (metabolism)
• Glomerular Filtration Rate (drug effects)
• Humans
• Immunosuppressive Agents (adverse effects)
• Liver Transplantation (adverse effects)
• Randomized Controlled Trials as Topic
• Renal Insufficiency (chemically induced)
• Sirolimus (adverse effects)
• Treatment Outcome