Synergistic Effects of Mycophenolate Mofetil (Mmf) and Sirolimus(rapamycin, Rapa) in Prevention of Acute Heart, Pancreas and Kidney Allograft Rejection and in Reversal of Ongoing Heart Allograft Rejection in the Rat

Vu, Minh Diem; Qi, Shijie; Xu, Dakang; Peng, Junzheng; Daloze, Pierre; Hadulco, S.; Aden, E R.; Leduc, Bertrand; Sehgal, Suren N.; Chen, H.

doi:10.1097/00007890-199805131-00673

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“…In the rat, the Combination of MMF and SRL was synergistic in preventing acute heart, pancreas and kidney allograft rejection [17]. The introduction of MMF as a treatment for rejection after liver transplantation has been described [7].…”

Section: Introductionmentioning

confidence: 99%

Sirolimus and mycophenolate mofetil after liver transplantation

Kniepeiss

Iberer

Grasser

et al. 2003

Transplant International

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Since the approval of sirolimus (SRL) as an immunosuppressive agent in renal transplantation, several liver transplant centres have introduced this agent to the immunosuppression regimen. We present here a retrospective followup study of late conversion to sirolimus and mycophenolate mofetil (MMF) as immunosuppressive agents after liver transplantation (LTX). From July 2001 to March 2002, seven liver transplant recipients (three female, 59 (41-66) years old) were enrolled in this study. Indications for liver transplantation were hepatitis B and/or hepatitis C (three), alcohol-induced cirrhosis (three) and Wilson's syndrome (hepatolenticular degeneration) (one). LTX was performed by standard (four) or piggy-back (three) technique. The switch to SRL was performed 62 (37-1 18) months after LTX; the reasons for the switch from cyclosporine or tacrolimus to SRL were renal (six) or neurological (one) impairment. As immunosuppressive therapy, SRL at trough levels of 4-10 ng/ml and MMF at trough levels of approximately 1 pg/ml were administered. Mean follow-up time under SRL per patient was 137 (26-258 days). Patient and graft survival was 100% during SRL therapy, and there were neither rejection episodes nor infections. Renal function improved in five of the six patients (83.3%) whom we had switched to SRL due to renal impairment. In the patient whom we switched to SRL due to neurological impairment, the neurological symptoms abated, and renal function improved. Side effects (hypertriglyceridaemia, hypercholesterolaemia, exanthema) became manifest in three patients (42.8%). Cessation of therapy due to side effects was necessary in two patients (exanthema: one, hypertriglyceridaemia: one). One patient refused to continue the therapy with SRL because he wanted tablets, and we only had SRL in fluid form. The data of our study suggest that SRL is a potent immunosuppressive agent of potential benefit in clinical LTX. SRL in combination with MMF provided sufficient immunosuppression of liver allografts in the late course after LTX. Side effects were reversible with dose reduction or cessation of therapy. We can thus conclude that SRL might offer an immunosuppressive therapy for patients with renal or neurological impairment after LTX.

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Section: Introductionmentioning

confidence: 99%