Efficacy of mycophenolate mofetil combined with very low-dose cyclosporine microemulsion in long-term liver-transplant patients with renal dysfunction.

Abstract

Cyclosporine (CsA)-induced renal dysfunction is common after liver transplantation. We evaluated the efficacy of tapering CsA to a very low dose and introducing mycophenolate mofetil (MMF) in long-term liver-transplant recipients with renal dysfunction. In addition, we assessed the impact of this strategy on calcineurin inhibition and on transforming growth factor (TGF)-beta levels. We prospectively enrolled 19 adult, long-term (>1 year) liver-transplant recipients with a decreased creatinine clearance greater than 25% compared with the first month posttransplant. MMF was introduced, and CsA was tapered to 25 mg twice daily. Calcineurin inhibition and TGF-beta were measured at baseline and 3 months thereafter. The CsA dose was tapered over 13+/-3 weeks. At 1-year follow-up, serum creatinine decreased from 141+/-24 to 105+/-22 micromol/L (P=0.002), creatinine clearance increased from 53+/-9 to 71+/-19 ml/min (P=0.02), and glomerular filtration rate increased from 40+/-13 to 64+/-18 mL/min (P=0.002). The incidence of acute rejection was 29%. Antihypertensive medications were discontinued in 71% of the patients. Although CsA levels decreased significantly, serum TGF-beta did not differ from normal controls, and calcineurin inhibition remained stable. The incidence of gastrointestinal side-effects and leukopenia was 18% and 24%, respectively. In long-term liver-transplant recipients with renal dysfunction, the introduction of MMF followed by tapering of CsA to a very low dose resulted in a significant improvement in renal function. However, this strategy maybe associated with a risk of acute rejection. The clinical pertinence of measuring serum TGF-beta levels and calcineurin inhibition remains to be determined.