Study Protocol: A Pilot Study to Determine the Safety and Efficacy of Induction-Therapy, De Novo MPA and Delayed mTOR-Inhibition in Liver Transplant Recipients with Impaired Renal Function. PATRON-Study

Patients older than 18 years with renal impairment at the time of liver transplantation eGFR < 50 ml/min and/or serum creatinine levels > 1.5 mg/dL will be included. Patients in will receive a CNI-free combination therapy (basiliximab, MMF, steroids and delayed Sirolimus). Primary endpoint is the incidence of steroid resistant acute rejection within the first 30 days after LT. The study is designed as prospective two-step trial requiring a maximum of 29 patients. In the first step, 9 patients will be included. If 8 or more patients show no signs of biopsy proven steroid resistant rejection, additional 20 patients will be included. If in the second step a total of 27 or more patients reach the primary endpoint the regimen is regarded to be safe and efficient.If a CNI-free-"bottom-up" IS strategy is safe and effective, this may be an innovative concept in contrast to classic top-down strategies that could improve the patient short and long-time renal function as well as overall complications and survival after LT. The results of PATRON07 may be the basis for a large multicenter RCT investigating the new "bottom-up" immunosuppressive strategy in patients with poor renal function prior to LT.http://www.clinicaltrials.gov webcite-identifier: NCT00604357Early renal dysfunction after liver transplantation (LT) is reported with a frequency as high as 50% [1,2]. The introduction of the MELD-based allocation system in the Eurotransplant area in December 2006 led to an increase of the proportion of liver transplant recipients with renal dysfunction at the time of transplantation, since creatinine became a key component for the allocation of liver allografts [3]. Major risk factors associated with early posttransplant renal impairment are: preexisting diabetes mellitus, time on the waiting list with end-stage hepatic disease, application of blood products, liver allograft dysfunction and toxicity of Calcineurin-inhibitors (CNI) [4-11]. The risk of developing chronic renal failu