A Comparison of Tacrolimus and Cyclosporine in Liver Transplantation: Effects on Renal Function and Cardiovascular Risk Status

Michael R. Lucey; Manal F. Abdelmalek; Rosemarie Gagliardi; Darla Granger; Curtis Holt; Igal Kam; Goran Klintmalm; Alan Langnas; Kirti Shetty; Andreas Tzakis; E. Steve Woodle


American Journal of Transplantation. 2005;5(5):1111-1119. 

In This Article

Abstract and Introduction

A retrospective chart review of 1065 consecutive liver allograft recipients in 11 centers from January 1997 to September 1998 was performed. Patients were followed for 3 years or until graft loss. Patients received either tacrolimus (n = 594), cyclosporine (n = 450) or no calcineurin inhibitor (n = 21). Model for end-stage liver disease (MELD) scores at time of transplant were similar between the two groups. During follow-up, more patients switched from cyclosporine to tacrolimus (26.7%) than from tacrolimus to cyclosporine (12.8%; p < 0.0001). Patient and graft survival were equivalent. Corticosteroid use was more common in cyclosporine-treated patients (p < 0.00001). Patients receiving tacrolimus experienced lower serum creatinine levels at months 3 through 36 (p < 0.0001). Systolic blood pressure was lower in patients receiving tacrolimus (p < 0.001) despite a reduced requirement for anti-hypertensive agents (p < 0.0001). In addition, tacrolimus was associated with lower total cholesterol and triglyceride levels for months 3 through 24 and 3 through 12, respectively (p < 0.01), despite a reduced requirement for anti-hyperlipidemic agents. The incidence of new-onset diabetes mellitus was similar in both groups. While both calcineurin inhibitors were associated with excellent patient and graft survival, renal function, blood pressure and serum lipid levels were significantly better with tacrolimus treatment.

Immunosuppression based on calcineurin inhibition with either cyclosporine or tacrolimus is standard of care in almost all primary liver allograft recipients in the United States.[1] Renal dysfunction and cardiovascular disease are significant causes of morbidity and mortality in long-term liver allograft recipients.[2,3] There is a 3-fold increase in relative risk of ischemic cardiac events in liver transplant recipients compared to age- and sex-matched populations, while the increase in relative risk for cardiac death in this population is 2.56.[3] Hyperlipidemia, hypertension and diabetes mellitus contribute to an increased risk for cardiovascular disease in liver allograft recipients.[4—7]

Although both cyclosporine and tacrolimus appear very efficacious in promoting graft survival, differential effects of these two medications on markers of renal and cardiovascular health have been reported. Several studies suggest a greater prevalence of hypertension, renal failure and/or hyperlipidemia in liver allograft recipients receiving cyclosporine compared to those treated with tacrolimus.[2,5—8] Conversely, new-onset diabetes mellitus has been reported to occur more commonly in liver recipients receiving tacrolimus rather than cyclosporine.[9,10] Consequently, we undertook a multicenter study of renal and cardiovascular toxicity profiles, including new-onset diabetes mellitus, in a large number of liver allograft recipients in routine clinical practice.