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MYCOPHENOLATE MOFETIL IN LIVER TRANSPLANT PATIENTS WITH CALCINEURIN-INHIBITOR-INDUCED RENAL IMPAIRMENT
H Ko, ED Greanya, TK Lee, U Steinbrecher, S Erb, EM Yoshida
Department of Medicine, University of British Columbia, Vancouver, British Columbia
BACKGROUND: Calcineurin inhibitors (CIs) provide effective immunosuppression after orthotopic liver transplantation (OLTx), but the associated nephrotoxicity can cause substantial long-term morbidity and mortality among transplant patients. In this study, we retrospectively investigated the efficacy and safety of mycophenolate mofetil (MMF) in OLTx patients with CI-induced renal impairment.
PATIENTS & METHODS: We reviewed medical records of all adult liver transplant recipients followed by Solid Organ Transplant Clinic at Vancouver General Hospital. Twenty-one (12 male, 9 female) patients were identified who converted to either MMF monotherapy, 1g twice daily (n=18) or with corticosteroids, <= 10mg prednisone (n=3) for CI-induced (14 cyclosporine, 6 tacrolimus) renal dysfunction. Six patients were excluded: one had sepsis contributing to renal dysfunction; two were started on dialysis before conversion; and three were switched back to CIs because of anemia, profound diarrhea and atrial fibrillation. Indications for OLTx were hepatitis C cirrhosis (3), primary biliary cirrhosis (3), primary sclerosing cholangitis (3), alcoholic cirrhosis (1), autoimmune hepatitis (2), and other diseases (3). Mean time from OLTx to conversion was 11.3 years and mean age was 60 years. Non-parametric Wilcoxon’s signed ranks test was used to determine whether there is a difference between the serum creatinine (SCr) before conversion and 3 or 6 months after conversion.
RESULTS: Median post-conversion follow-up was 294 days (range 35-1103). The median SCr was significantly reduced from 144 umol/L (N=15) before conversion to 129 umol/L (N=13) at 3 months and 139 umol/L (N=9) at 6 months follow-up (p = 0.001 and 0.008, respectively). MMF was well tolerated, and no adverse graft outcomes were documented. Only three (20%) patients displayed adverse events: one (7%) had some liver enzymes elevation and required the addition of sirolimus while two (13%) had GI intolerance.
CONCLUSIONS: CI free regimens with MMF treatment appear to be a safe alternative for stable OLTx recipients with CI-induced nephrotoxicity. Side effects were uncommon; however, longer follow-up and larger patient population are needed in the future to better determine the efficacy and safety of MMF.