Impact of combined mycophenolate mofetil and low-dose calcineurin inhibitor therapy on renal function, cardiovascular risk factors, and graft function in liver transplant patients: Preliminary results of an open prospective study

Abstract

As liver transplantation (LT) is now being performed with excellent 1-year graft survival rates of 85% to 90%, attention has been shifted to reducing long-term complications of calcineurin inhibitors (CNI). We randomized LT patients (2:1) who displayed renal dysfunction under CNI treatment to either mycophenolate mofetil (MMF) (1000 mg twice a day) followed by stepwise reduction of CNI ( n = 21; Tac trough levels <4 ng/mL, CsA trough levels <50 ng/mL); or continue their current CNI dose ( n = 11; control group). Three months after study entry, we observed significantly decreased mean values in the CNI reduction group of serum creatinine (1.88 ± 0.36 versus 1.58 ± 0.33 mg/dL, P < .001) and BUN (39.2 ± 11.8 versus 29.9 ± 9.59 mg/dL, P < .001) with a significantly increased GFR (51.4 ± 10.8 versus 61.6 ± 14.1 mL/min, P < .001). Improved renal function in these long-term LT recipients (5.6 ± 3.6 years posttransplant; range, 2 to 13 years) suggests at least a partial reversibility of CNI-induced renal damage. Furthermore, we found an improved lipid profile as well as a significantly decreased mean systolic (140 ± 19 versus 130 ± 14 mm Hg, P < .01) and diastolic (82 ± 9 to 74 ± 8 mm Hg, P < .001) blood pressure 3 months after introduction of MMF therapy. Additionally, transaminases significantly improved in the CNI reduction group within this time period (ALT 37.9 ± 25.9 versus 25.2 ± 13.2, P < .05). MMF and CNI-reduced immunosuppressive regimens may improve long-term patient survival, suggesting a broad application within the liver transplant setting.