Abstract
BackgroundImmunosuppression with calcineurin inhibitors (CNI) increases the risk of renal dysfunction after orthotopic liver transplantation (OLT). Controlled trials have shown improvement of renal function in patients that received delayed and/or reduced-dose CNI after OLT. Delaying immunosuppression with CNI in combination with induction therapy does not increase the risk of acute rejection but reduces the incidence of acute renal dysfunction. Based on this clinical data this study protocol was designed to assess the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation.Methods/DesignA prospective therapeutic exploratory, non-placebo controlled, two stage monocenter trial in a total of 29 liver transplant patients was designed to assess the safety and efficacy of de-novo CNI-free immunosuppression with basiliximab, mycophenolate sodium, prednisolone and everolimus. The primary endpoint is the rate of steroid resistant rejections. Secondary endpoints are the incidence of acute rejection, kidney function (assessed by incidence and duration of renal replacement therapy, incidence of chronic renal failure, and measurement glomerular filtration rate), liver allograft function (assessed by measurement of AST, ALT, total bilirubin, AP, GGT), treatment failure, (i. e., re-introduction of CNI), incidence of adverse events, and mortality up to one year after OLT.DiscussionThis prospective, two-stage, single-group pilot study represents an intermediate element of the research chain. If the data of the phase II study corroborates safety of de-novo CNI-free immunosuppressive regimen this should be confirmed in a randomized, prospective, controlled double-blinded clinical trial. The exploratory data from this trial may then also facilitate the design (e. g. sample size calculation) of this phase III trial.Trial registration numberNCT00890253 (clinicaltrials.gov)
Highlights
Immunosuppression with calcineurin inhibitors (CNI) increases the risk of renal dysfunction after orthotopic liver transplantation (OLT)
After OLT more than 90% of patients receive an immunosuppressive regimen based on calcineurin inhibitors (CNI), i. e., cyclosporine A(CsA) or tacrolimus (TAC) [3]
Pathophysiology of CNI-induced nephropathy Despite major differences in the chemical structure, both, TAC and CsA, seem to cause nephropathy characterized by vasoconstriction of renal arterioles [4]
Summary
Immunosuppression with calcineurin inhibitors (CNI) increases the risk of renal dysfunction after orthotopic liver transplantation (OLT). Delaying immunosuppression with CNI in combination with induction therapy does not increase the risk of acute rejection but reduces the incidence of acute renal dysfunction Based on this clinical data this study protocol was designed to assess the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation. The clinical manifestations of this acute renal dysfunction include reduction in glomerular filtration rate (GFR), hypertension, hyperkalemia, tubular acidosis, increased reabsorption of sodium and oliguria [8]. This acute form of CNI toxicity may be reversed when CNI administration is reduced or withdrawn. The chronic form of CNI-induced nephrotoxicity is characterized by renal vasoconstriction and by the development of structural damage, including arteriolopathy and tubulointerstitial fibrosis, which is irreversible and may lead to end-stage renal disease [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
