Long-term outcome of conversion to sirolimus monotherapy after liver transplant.
OBJECTIVE
This study sought to assess the long-term efficacy and safety of conversion from a calcineurin inhibitor-based immunosuppressive regimen to sirolimus monotherapy in liver transplant recipients with renal dysfunction.


METHODS
Twenty-five liver transplant recipients with calcineurin inhibitor-based immunosuppression were included in this single-center, 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 episodes 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 follow-up. 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.
Second Department of Surgery, University of Leipzig, Germany.
Dirk
D
Uhlmann
Tonja
T
Weber
Stefan
S
Ludwig
Barbara
B
Ludwig
Michael
M
Bartels
Johann
J
Hauss
Sven
S
Jonas
Helmut
H
Witzigmann
D000328:Adult; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D007668:Kidney / Q000503:physiopathology*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus