Improvement of renal function after conversion to mycophenolate mofetil combined with low-level calcineurin inhibitor in liver transplant recipients with chronic renal dysfunction.

Abstract

Calcineurin inhibitors (CNI) are the main pathogenic factors for renal dysfunction in solid organ transplant recipients. Introduction of non-nephrotoxic immunosuppressive drugs, such as mycophenolate mofetil (MMF), may allow discontinuation or reduction of CNI treatment, thereby improving renal function. The aim of this study was to assess the feasibility, efficacy and safety of MMF introduction and CNI dosage reduction in the maintenance immunosuppressive protocol to improve renal function in liver transplant recipients with chronic renal dysfunction.
We prospectively included 88 liver transplant recipients including 74 men and an overall mean age of 58.8 +/- 10.3 years who all displayed chronic renal dysfunction (creatinine >1.4 mg/dL) and proteinuria <1 g/d. They were subdivided into 3 groups according to the basal creatinine value 1.4-1.7 mg/dL (group I; n = 41); 1.8-2.0 mg/dL (group II; n = 28); and >2 mg/dL (group III; n = 19). MMF was initiated at 1.5-2.0 g/d. Reduction of tacrolimus or cyclosporine dosage was performed to achieve respective target trough levels of <5 ng/mL or <50 ng/mL. We performed periodic determinations of arterial pressure, liver function tests, serum creatinine, blood cells count, CNI levels, and proteinuria.
Creatinine values after conversion were 1.4 +/- 0.5 mg/dL in the overall group. Improvement of renal function was more frequent among groups I (80.4%) and II (92.8%) versus III (73.6%). Normalization of creatinine values was more frequent in group I (68.2%) with respect to cohorts II (21.4%) and III (10.5%). Rejection was not detected.
Application of an immunosuppressive protocol with MMF and low-level CNI in liver transplant recipients with chronic renal dysfunction was associated with improvement or normalization of creatinine, without an increased risk of rejection. Early conversion is needed to achieve the best results.