Abstract
Calcineurin inhibitors (CNIs) are frequently given at a reduced dose in combination with mycophenolate mofetil (MMF) to avoid nephrotoxicity, but the optimal reduction in CNI dose has not been established. In this prospective, open-label, multicenter study, liver transplant recipients with chronic renal dysfunction who were administered a CNI-based immunosuppressive regimen were included in the intent-to-treat (ITT) population. The primary endpoint was declination in renal function, which was defined as a ≥ 20% decrease in the glomerular filtration rate during the year following regimen adjustment. In the ITT population, renal function declined after regimen adjustment in three patients (7%) in the MMF plus 50% CNI reduction group. Additionally, three of 40 patients (7.5%) in the MMF plus 75% CNI reduction group experienced at least one clinically suspected or biopsy-proven acute rejection. There were no differences between the two groups. The corrected mean improvement in creatinine clearance at week 52 was 6.551 mL/min in the MMF plus 50% CNI reduction group and 6.442 mL/min in the MMF plus at least 75% CNI reduction group. Thus, a regimen of MMF combined with a 50% or at least 70% reduction in CNI dose could improve renal function and was both tolerable and safe.
Highlights
Liver transplantation (LT) is a highly successful treatment for end-stage liver disease and select hepatocellular carcinoma patients
We evaluated whether the conversion of LT recipients with chronic renal dysfunction to treatment with mycophenolate mofetil (MMF) in combination with Calcineurin inhibitors (CNIs) at a reduced dose (e.g. 50% or 75%) could improve renal function in LT recipients without increasing the risk of rejection or adverse events (AEs)
Our results are consistent with those of previous studies, which have demonstrated the efficacy of MMF combined with CNI dose reduction for preventing renal dysfunction in LT recipients [12, 21, 22, 25, 27]
Summary
Liver transplantation (LT) is a highly successful treatment for end-stage liver disease and select hepatocellular carcinoma patients. Hypertension, diabetes, treatment with immunosuppressants, hepatitis C virus infection, and calcineurin inhibitor (CNI) toxicity are frequent comorbidities in LT recipients that can lead to renal dysfunction. CNI toxicity is the primary cause of chronic renal dysfunction [3, 4, 8, 9]. Multicenter, randomized study performed by Pageaux et al [12], MMF in combination with at least a 50% reduction in CNI dose significantly improved renal function in LT recipients at 1 year without causing rejection. No improvement in renal function was observed in LT recipients who received a less than 25% reduction in CNI dose without the addition of MMF. In another prospective, randomized pilot trial, Gerhardt et al [23] demonstrated that MMF in combination with a 75% dose reduction in CNI could improve the glomerular filtration rate (GFR) in LT recipients with moderately elevated serum creatinine (SCr) levels
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