Replacement of calcineurin inhibitors with mycophenolate mofetil in liver-transplant patients with renal dysfunction: a randomised controlled study

Background Renal dysfunction is a major complication of long-term immunosup pressive therapy with calcineurin inhibitors (CNI) in liver-transplant reci pients. We undertook a randomised study to assess the safety and efficacy o f CNI withdrawal and replacement by mycophenolate mofetil. Methods 28 people who had had renal dysfunction attributable to suspected C NI toxicity after liver transplantation participated in the study. We repla ced CNI with mycophenolate mofetil in a stepwise pattern in half the group (study patients); the other half (controls) stayed on CNI immunosuppression . Renal function, blood pressure, uric acid, and blood lipids were measured before and 6 months after study entry. Side-effects of medication and graf t function were recorded throughout the study. Findings At the end of the study, mean (SD) serum creatinine had fallen by 44.4 (48.7) mu mol/L in study patients compared with 3.1 (14.3) mu mol/L in controls; a mean difference of 41.3 mu mol/L (95% CI 12.4-70.2). Moreover, systolic and diastolic blood pressure, and serum uric acid decreased signi ficantly in the study group but not in the control group (mean [95% CI] bet ween group differences 10.8 mm Hg [3.0-18.6], 5.0 mm Hg [0.9-9.2], and 83.1 mu mol/L [12.7-153.6], respectively). There were no changes in cholesterol or triglyceride concentrations in either group. Side-effects were reported by eight of the study patients. Three reversible episodes of acute graft r ejection occurred in study patients during mycophenolate mofetil monotherap y, whereas none occurred in the control group. Interpretation Substitution of CNI by mycophenolate mofetil can improve ren al function, blood pressure, and uric acid concentration of liver-transplan t patients, but there is an increased rejection risk with mycophenolate mof etil monotherapy.