The Efficacy and Limitations of Sirolimus Conversion in Liver Transplant Patients Who Develop Renal Dysfunction on Calcineurin Inhibitors

Lam, Patrick; Yoshida, Atsushi; Brown, Kimberly; Abouljoud, Marwan; Bajjoka, I; Dagher, Fadi; Moonka, Dilip

doi:10.1023/b:ddas.0000034567.53748.df

Cited by 31 publications

(23 citation statements)

References 10 publications

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“…Dyslipidemia was reported in up to 44% of patients. 12,47,48 In 4 of our patients, slight adverse effects (thrombocytopenia, gingival hyperplasia, oral ulceration) occurred. Only 1 patient had to have sirolimus therapy withdrawn because of acneiform rash, and treatment was converted to everolimus.…”

Section: Discussionmentioning

confidence: 72%

“…[12][13][14] Unfortunately, the follow-up of most of the studies was relatively short, often less than 12 months. Therefore, it is uncertain if the initial increase in creatinine clearance will be sustained over a longer time.…”

Section: Discussionmentioning

confidence: 99%

“…In recent nonrandomized trials, investigators have shown that replacement of CNIs by sirolimus in patients receiving liver, kidney, and heart transplants can improve renal function in selected patients. [11][12][13][14] Other benefits of sirolimus are favorable effects on posttransplant hypertension and antitumor activity. 15,16 On the other hand, relevant adverse effects of sirolimus in liver transplant recipients have been reported by Montalbano and associates.…”

Section: Long-term Outcome Of Conversion To Sirolimus Monotherapy Aftmentioning

confidence: 99%

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Long-term Outcome of Conversion to Sirolimus Monotherapy After Liver Transplant

Uhlmann

Weber²,

Ludwig³

et al. 2012

Exp Clin Transplant

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Objectives: This study sought to assess the longterm efficacy and safety of conversion from a calcineurin inhibitor-based immunosuppressive regimen to sirolimus monotherapy in liver transplant recipients with renal dysfunction. Materials and Methods: Twenty-five liver transplant recipients with calcineurin inhibitor-based immunosuppression were included in this singlecenter, prospective study. Indications were renal dysfunction, avoidance of tumor recurrence, combination renal dysfunction and avoidance of tumor recurrence, and calcineurin inhibitor-related adverse effects. Results: Mean interval between liver transplant and initiation of sirolimus monotherapy was 51.7 months. The mean follow-up was 75.6 months. The mean ± SD sirolimus whole-blood trough level was 9.0 ± 2.8 ng/mL after 6 months and 6.0 ± 1.8 ng/mL after 18 months. No rejection episode occurred. There was an improvement of the mean creatinine level: 156.1 ± 54.9 µmol/L before conversion versus 129.1 ± 34.7 µmol/L approximately 3 years after conversion (P < .05). The glomerular filtration rate, measured by technetium Tc-99m-diethylenetriamine penta acetic aerosol scintigraphy, improved from 27.4 ± 6.8 mL/min/1.73 m 2 before conversion to 43.3 ± 6.3 mL/min/1.73 m 2 at final follow-up. Proteinuria increased after conversion to sirolimus after 6 months (P < .05) and at last follow-up. The systolic blood pressure decreased from 151.5 ± 20.2 to 132.1 ± 19.4 mm Hg, and the diastolic from 89.7 ± 11.2 to 82.1 ± 9.1 mm Hg at last followup. Serum cholesterol and serum triglyceride levels were nearly unchanged. However, 50% of the patients were treated with lipid-lowering agents. Four patients had sirolimus-induced adverse effects (thrombocytopenia, gingival hyperplasia, oral ulceration). Conclusions: Conversion from calcineurin inhibitors to sirolimus monotherapy after liver transplant results in stabilization of renal function in 75% to 85% of cases and of blood pressure, without increased risk of rejection. The spectrum of adverse effects is low.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Long-term Outcome Of Conversion To Sirolimus Monotherapy Aftmentioning

confidence: 99%

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Long-term Outcome of Conversion to Sirolimus Monotherapy After Liver Transplant

Uhlmann

Weber²,

Ludwig³

et al. 2012

Exp Clin Transplant

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“…Again, sirolimus conversion should be initiated early since late conversion rarely improves chronic renal dysfunction [49] . In fact, several studies have shown that in patients with preexisting renal disease, sirolimus can worsen nephrotoxicity and promote proteinuria [5052] .…”

Section: Mtor Inhibitorsmentioning

confidence: 99%

Overview of immunosuppression in liver transplantation

Pillai¹,

Levitsky²

2009

WJG

105

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Continued advances in surgical techniques and immunosuppressive therapy have allowed liver transplantation to become an extremely successful treatment option for patients with end-stage liver disease. Beginning with the revolutionary discovery of cyclosporine in the 1970s, immunosuppressive regimens have evolved greatly and current statistics confirm one-year graft survival rates in excess of 80%. Immunosuppressive regimens include calcineurin inhibitors, anti-metabolites, mTOR inhibitors, steroids and antibody-based therapies. These agents target different sites in the T cell activation cascade, usually by inhibiting T cell activation or via T cell depletion. They are used as induction therapy in the immediate periand post-operative period, as long-term maintenance medications to preserve graft function and as salvage therapy for acute rejection in liver transplant recipients. This review will focus on existing immunosuppressive agents for liver transplantation and consider newer medications on the horizon.

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“…Sirolimus can limit or even avoid the adverse effects of calcineurin inhibitors and simultaneously guarantee adequate immunosuppression. [3][4][5][6] There are 2 regimens for converting to sirolimus from calcineurin inhibitors in liver transplant. 5 One is partial conversion by combining low-dose sirolimus with reduced calcineurin inhibitors, which was used in most studies of the early trials.…”

Section: Discussionmentioning

confidence: 99%

Sirolimus Conversion in Liver Transplant Recipients With Calcineurin Inhibitor-Induced Complications: Efficacy and Safety

Ju¹,

Guo²,

Liang³

et al. 2012

Exp Clin Transplant

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Objectives: To evaluate the efficacy and safety of conversion from calcineurin inhibitors to sirolimus among liver transplant recipients with calcineurin inhibitor-induced complications. Materials and Methods: After receiving liver transplants, 25 patients with calcineurin inhibitorinduced complications (22 renal dysfunction and 3 new-onset diabetes mellitus) were converted from sirolimus to tacrolimus. The serum creatinine, sirolimus trough level, liver function, acute rejection episodes, and drug-related adverse effects were monitored. Results: The patients were followed for 12 to 50 months (median, 25 months). The renal function of the 22 patients with renal dysfunction improved after sirolimus conversion. The serum creatinine levels were significantly lower at 3 months after conversion versus before conversion (113.2 ± 21.8 µmol/L vs 163.2 ± 45.3 µmol/L; P < .05). At the end of the follow-up, the average serum creatinine level was 101.9 ± 23.4 µmol/L among the 20 living recipients. Diabetes also was under control in 3 diabetic recipients after the conversion. Four patients experienced episodes of acute rejection, and intravenous steroid bolus therapy was administered in 2 of them. No graft was lost because of acute rejection. The adverse effects of sirolimus included hyperlipidemia (7/25), anemia (8/25), and mouth ulcers (9/25). All these adverse effects were relieved after a short-term symptomatic therapy, and no patient was withdrawn from the conversion trial. Conclusions: Sirolimus monotherapy is effective and safe in liver transplant recipients. Conversion to sirolimus was associated with a sustained improvement in renal function and diabetes mellitus without an increased incidence of acute rejection episodes.

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The Efficacy and Limitations of Sirolimus Conversion in Liver Transplant Patients Who Develop Renal Dysfunction on Calcineurin Inhibitors

Cited by 31 publications

References 10 publications

Long-term Outcome of Conversion to Sirolimus Monotherapy After Liver Transplant

Long-term Outcome of Conversion to Sirolimus Monotherapy After Liver Transplant

Overview of immunosuppression in liver transplantation

Sirolimus Conversion in Liver Transplant Recipients With Calcineurin Inhibitor-Induced Complications: Efficacy and Safety

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