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

<p>Abstract</p> <p>Background</p> <p>Patients undergoing liver transplantation with preexisting renal dysfunction are prone to further renal impairment with the early postoperative use of Calcineurin-inhibitors. However, there is only little scientific evidence for the safety and efficacy of de novo CNI free "bottom-up" regimens in patients with impaired renal function undergoing liver transplantation. This is a single-center study pilot-study (<b>PATRON07</b>) investigating safety and efficacy of CNI-free, "bottom-up" immunosuppressive (IS) strategy in patients undergoing liver transplantation (LT) with renal impairment prior to LT.</p> <p>Methods/Design</p> <p>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.</p> <p>Discussion</p> <p>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 <b>PATRON07 </b>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.</p> <p><url>http://www.clinicaltrials.gov</url>-identifier: NCT00604357</p

Novel prediction score including pre- and intraoperative parameters best predicts acute kidney injury after liver surgery

BACKGROUND: A recently published score predicts the occurrence of acute kidney injury (AKI) after liver resection based on preoperative parameters (chronic renal failure, cardiovascular disease, diabetes, and alanine-aminotransferase levels). By inclusion of additional intraoperative parameters we aimed to develop a new prediction model. METHODS: A series of 549 consecutive patients were enrolled. The preoperative score and intraoperative parameters (blood transfusion, hepaticojejunostomy, oliguria, cirrhosis, diuretics, colloids, and catecholamine) were included in a multivariate logistic regression model. We added the strongest predictors that improved prediction of AKI compared to the existing score. An internal validation by fivefold cross validation was performed, followed by a decision curve analysis to evaluate unnecessary special care unit admissions. RESULTS: Blood transfusions, hepaticojejunostomy, and oliguria were the strongest intraoperative predictors of AKI after liver resection. The new score ranges from 0 to 64 points predicting postoperative AKI with a probability of 3.5-95 %. Calibration was good in both models (15 % predicted risk vs. 15 % observed risk). The fivefold cross-validation indicated good accuracy of the new model (AUC 0.79 (95 % CI 0.73-0.84)). Discrimination was substantially higher in the new model (AUCnew 0.81 (95 % CI 0.76-0.86) versus AUCpreoperative 0.60 (95 % CI 0.52-0.69), p < 0.001). The new score could reduce up to 84 unnecessary special care unit admissions per 100 patients depending on the decision threshold. CONCLUSIONS: By combining three intraoperative parameters with the existing preoperative risk score, a new prediction model was developed that more accurately predicts postoperative AKI. It may reduce unnecessary admissions to the special care unit and support management of patients at higher risk

The relationship between preoperative creatinine clearance and outcomes for patients undergoing liver transplantation: a retrospective observational study

BACKGROUND: Renal failure with following continuous renal replacement therapy is a major clinical problem in liver transplant recipients, with reported incidences of 3% to 20%. Little is known about the significance of postoperative acute renal failure or acute-on-chronic renal failure to postoperative outcome in liver transplant recipients. METHODS: In this post hoc analysis we compared the mortality rates of 135 consecutive liver transplant recipients over 6 years in our center subject to their renal baseline conditions and postoperative RRT. We classified the patients into 4 groups, according to their preoperative calculated Cockcroft formula and the incidence of postoperative renal replacement therapy. Data then were analyzed in regard to mortality rates and in addition to pre- and peritransplant risk factors. RESULTS: There was a significant difference in ICU mortality (p=.008), hospital mortality (p=.002) and cumulative survival (p<.0001) between the groups. The highest mortality rate occurred in the group with RRT and normal baseline kidney function (20% ICU mortality, 26.6% hospital mortality and 50% cumulative 1-year mortality, respectively). The hazard ratio in this group was 9.6 (CI 3.2-28.6, p=.0001). CONCLUSION: This study shows that in liver transplant recipient's acute renal failure with postoperative RRT is associated with mortality and the mortality rate is higher than in patients with acute-on-chronic renal failure and postoperative renal replacement therapy