Mycophenolate mofetil for renal dysfunction in liver transplant recipients on cyclosporine or tacrolimus: randomized, prospective, multicenter pilot study results

Abstract

Background: Liver transplantation (LTX) recipients with renal dysfunction may benefit from mycophenolate mofetil (MMF) and reduction or discontinuation of nephrotoxic calcineurin inhibitors (CNI). The authors report the first randomized, multicenter pilot studies of this approach (one study for patients on cyclosporine [CsA] and one for those on tacrolimus [Tac]).

Methods: Patients 3 to 27 months post-LTX with greater than 20% reduced renal function since LTX, and creatinine 1.8 to 4.0 mg/dL, creatinine clearance 20 to 60 mL/min, or both, were randomized to discontinuation (group 1) or 50% reduction (group 2) of CNI dose, together with MMF 1.5 g administered twice daily and prednisone. Endpoints included measured glomerular filtration rate (GFR) 52 weeks after study entry and biopsy-proven rejection.

Results: In the CsA and Tac trials, 15 and 12 patients, respectively, completed the 52-week follow-up. In the CsA trial, the mean GFR at baseline and week 52 were 35.0 and 57.8 mL/min (>15% improvement, five of six; unchanged, one of six) for group 1 and 46.0 and 63.8 mL/min (>15% improvement, four of nine; unchanged, three of nine; >15% deterioration, two of nine) for group 2. In the Tac trial, GFRs were 55.4 and 56.0 mL/min (>15% improvement, two of five; unchanged, three of five) for group 1 and 46.7 and 60.2 mL/min (>15% improvement, four of seven; unchanged, three of seven) for group 2. Mild or moderate rejection occurred in 38% and 9% of patients in groups 1 and 2 of the CsA trial and in 14% of each group of the patients in the Tac trial.

Conclusions: These pilot studies show that in LTX recipients with renal dysfunction, MMF allows CNI dose reduction or discontinuation, improving or stabilizing GFR in most patients.