Case Report: Sirolimus Therapy in Orthotopic Liver Transplant (OLT) Recipients with Acute Renal Insufficiency

Montalbano, Marzia; Neff, Guy; Slapak-Green, Grabriella; Berney, Thierry; Meyer, Douglas

doi:10.1007/s10620-004-9606-z

Cited by 5 publications

(9 citation statements)

References 10 publications

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“…In all, 11 studies (3 randomized controlled trials24‐26 and 8 observational studies17, 27‐33) were included for the systematic review and meta‐analysis. For two of these studies, the authors provided recently accepted unpublished manuscripts 24, 29.…”

Section: Resultsmentioning

confidence: 99%

“…Two studies had separate subgroups of patients who underwent early initiation (<6 months) 29, 33. The comparison group received only a CNI,17, 24‐26, 28, 29 a CNI and MMF,27, 33 or only MMF 30, 31. Zaghla et al's study32 had two sirolimus arms: (1) sirolimus alone with or without MMF and (2) sirolimus and a CNI with or without MMF.…”

Section: Resultsmentioning

confidence: 99%

“…The comparison groups in all observational studies consisted of LT recipients who did not receive sirolimus. The comparability of the sirolimus and comparison groups was determined by restriction in three of the six studies 17, 28, 32. No other method for ensuring comparability (adjustments for confounders, stratification, or multivariable analysis) was described for the other studies.…”

Section: Resultsmentioning

confidence: 99%

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Use of Sirolimus in Liver Transplant Recipients with Renal Insufficiency: A Systematic Review and Meta-Analysis

et al. 2010

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Background Sirolimus is used in patients with renal insufficiency following liver transplantation (LT), especially in those with calcineurin inhibitor (CNI) associated nephrotoxicity. Aims We conducted a systematic review of all randomized controlled trials (RCTs) and observational studies to test the hypothesis that use of sirolimus is associated with an improvement in renal function at 1 year in LT recipients with renal insufficiency (GFR<60ml/min or creatinine≥1.5mg/dL). Methods 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 utilized 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. Results Eleven studies (3 RCTs and 8 observational) met final inclusion criteria. A non significant improvement of 3.38 ml/min (95% CI -2.93 to 9.69) was observed among methodologically sound observational studies and controlled trials reporting the primary outcome. Among controlled trials, sirolimus use was associated with a 10.35 ml/min (95% CI 3.98 - 16.77) improvement in GFR or creatinine clearance. Sirolimus was not significantly associated with death, RR=1.12 (95% CI 0.66-1.88) or graft failure, RR=0.80 (95% CI 0.45-1.41), though 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 CNI is associated with a non significant improvement in renal function in LT recipients with renal insufficiency, though results are limited by heterogeneity, risk of bias, and lack of standardized reporting.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Use of Sirolimus in Liver Transplant Recipients with Renal Insufficiency: A Systematic Review and Meta-Analysis

et al. 2010

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“…There are now many published studies reporting single center experiences with converting liver transplant patients from a CNI based regimen to an SRL based regimen with a goal to recover renal function (5–7, 9, 11, 12, 16, 17, 20, 21). The majority of liver transplant recipients in these reports had CNI withdrawal after the first year post‐transplant.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous single center reports have shown the utility of using SRL as an alternative option to CNI in non-renal transplant recipients. There are conflicting data as to whether or not SRL conversion improves renal function in the liver transplant population (5)(6)(7)(8)(9)(10)(11)(12).…”

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confidence: 99%

Timing of sirolimus conversion influences recovery of renal function in liver transplant recipients

Rogers¹,

Johnson²,

Mandelbrot³

et al. 2009

Clinical Transplantation

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The long-term use of calcineurin inhibitors (CNI) leads to renal dysfunction in many liver transplant (LT) recipients. The purpose of this analysis is to evaluate renal function in patients converted from CNI to sirolimus (SRL). From May 2002-November 2006, 137 LT were performed in 125 patients, 72 of which were converted to SRL. Evaluation of SRL conversion was stratified by early conversion (<90 d from LT) (EC) vs. late conversion (LC). Renal function was evaluated using the six-point modification of diet in renal disease formula (estimated glomerular filtration rate [eGFR]). Forty-two patients on SRL and 40 on CNI had at least three months of follow-up and are included in the eGFR evaluation. At all time points after conversion, the EC group demonstrated a significantly higher mean eGFR than those in the LC group. A significant improvement in eGFR was seen within the EC group when comparing eGFR at time of conversion to eGFR at three, six, nine, and 12 months after conversion and last follow-up. The only improvement in the LC group was from conversion to the three-month time point. We conclude that EC to SRL results in a profound improvement in eGFR that begins at three months and is sustained beyond one yr.

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Sirolimus Conversion in Liver Transplant Recipients With Renal Dysfunction: A Prospective, Randomized, Single-Center Trial

et al. 2007

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This pilot trial was designed to assess the safety and efficacy of SRL in liver transplant recipients with renal dysfunction. Forty patients with renal dysfunction (24-hr CrCl 40-80 mL/min) were randomized to be withdrawn from the calcineurin inhibitor (CNI) and receive sirolimus (SRL) or to continue CNI (control arm). Improvement in 24-hour CrCl was seen in the SRL arm at 3 months (75 mL/min SRL vs. 56 mL/min control, P=0.012), whereas at 12 months there was a trend toward improvement in the SRL arm (72 mL/min SRL vs. 58 mL/min control, P=0.09). Two patients, one in each arm, developed steroid-sensitive rejection. Side effects of SRL were limited and included hyperlipidemia requiring treatment (15%), pruritus (5%), and mouth sores (25%). In this trial, SRL-based immunosuppression was a safe alternative to CNI. Although early improvements were observed, withdrawing CNI and replacing it with SRL did not result in a statistically significant improvement in renal function at 12 months of follow-up.

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Case Report: Sirolimus Therapy in Orthotopic Liver Transplant (OLT) Recipients with Acute Renal Insufficiency

Cited by 5 publications

References 10 publications

Use of Sirolimus in Liver Transplant Recipients with Renal Insufficiency: A Systematic Review and Meta-Analysis

Use of Sirolimus in Liver Transplant Recipients with Renal Insufficiency: A Systematic Review and Meta-Analysis

Timing of sirolimus conversion influences recovery of renal function in liver transplant recipients

Sirolimus Conversion in Liver Transplant Recipients With Renal Dysfunction: A Prospective, Randomized, Single-Center Trial

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