Serum alkaline phosphatase and bilirubin are early surrogate markers for ischemic cholangiopathy and graft failure in liver transplantation from donation after circulatory death.

Liver transplantation with the use of donation after circulatory death (DCD) is associated with ischemic cholangiopathy (IC) often leading to graft loss. We hypothesized that serial postoperative analysis of alkaline phosphatase and bilirubin might identify patients who would later on develop ischemic cholangiopathy and/or graft loss, allowing early recognition and potentially retransplantation. The University of Washington DCD experience totals 89 DCD liver transplantations performed from 2003 to 2011 with Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively; 84/89 patients transplanted with DCD livers lived ≥ 60 days after transplantation and were analyzed. Serum bilirubin and alkaline phosphatase levels at 1 week, 2 week, 1 month, and 2 months after transplantation were analyzed. Two-month serum bilirubin and alkaline phosphatase proved to have the strongest associations with development of IC and graft failure. Two-month alkaline phosphatase of <100 U/L had a negative predictive value of 97% for development of IC. Two-month alkaline phosphatase demonstrated an inflection starting at >300 U/L strongly associated with development of IC (P < .0001). Serum bilirubin at 2 months was most strongly associated with graft failure within the 1st year with a strong inflection point at 2.5 mg/dL (P = .0001). All jaundiced recipients at 60 days after transplantation (bilirubin >2.5 mg/dL) developed graft failure within the 1st year (P < .0001). Use of these early surrogate markers could facilitate prioritization and early retransplantation for DCD liver recipients with allografts destined for failure.

Differential rates of ischemic cholangiopathy and graft survival associated with induction therapy in DCD liver transplantation.

Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. The University of Washington (UW) DCD experience totals 89 DCD liver transplants performed between 2003 and 2011. Overall outcome after DCD liver transplantation at UW demonstrates Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively, with the great majority of patient and graft losses occurring in the first-year posttransplant from IC. Our program has almost exclusively utilized either anti-thymocyte globulin (ATG) or basiliximab induction (86/89) for DCD liver transplantations. Analysis of the differential effect of induction agent on graft survival demonstrated graft survival of 96.9% at 1 year for ATG versus 75.9% for basiliximab (p = 0.013). The improved survival did not appear to be from a lower rate of rejection (21.9% vs. 22.2%) but rather a differential rate of IC, 35.2% for basiliximab versus 12.5% for ATG (p = 0.011). Multivariable analysis demonstrated induction agent to be independently associated with graft survival and IC free graft survival when analyzed against variables including donor age, fWIT, donor cold ischemia time and transplant era.

Risk stratification of kidneys from donation after cardiac death donors and the utility of machine perfusion.

There has been a dramatic increase in the utilization of kidneys from donors after cardiac death (DCD). While these organs represent an opportunity to expand the donor pool, the assessment of risk and optimal perioperative management remains unclear. Our primary aim was to identify risk factors for objective outcomes, and secondarily, we sought to determine what impact pulsatile machine perfusion (PMP) had on these outcomes. From 1993 to November 2008, 6057 DCD kidney transplants were reported to the Organ Procurement and Transplantation Network database, with complete endpoints for delayed graft function (DGF) and graft survival (GS). Risk factors were identified using a multivariable regression analysis adjusted for recipient factors. Age (50 yr) [OR 1.81, p < 0.0001] and cold ischemia time (CIT) (>30 h) [OR 3.22, p < 0.0001] were the strongest predictors of DGF. The use of PMP decreased the incidence of DGF only when donor age was >60 yr and improved long-term graft survival when donor age was >50 yr. Donor warm ischemia time >20 min was also found to correlate with increased DGF. While the incidence of DGF in DCD kidneys is significantly higher, the only factors the transplant surgeon can control are CIT and the use of PMP. The data suggest that the use of PMP in DCD kidneys <50 yr old provides little clinical benefit and may increase CIT.

D-MELD, a simple predictor of post liver transplant mortality for optimization of donor/recipient matching.

Numerous donor and recipient risk factors interact to influence the probability of survival after liver transplantation. We developed a statistic, D-MELD, the product of donor age and preoperative MELD, calculated from laboratory values. Using the UNOS STAR national transplant data base, we analyzed survival for first liver transplant recipients with chronic liver failure from deceased after brain death donors. Preoperative D-MELD score effectively stratified posttransplant survival. Using a cutoff D-MELD score of 1600, we defined a subgroup of donor-recipient matches with significantly poorer short- and long-term outcomes as measured by survival and length of stay (LOS). Avoidance of D-MELD scores above 1600 improved results for subgroups of high-risk patients with donor age >/=60 and those with preoperative MELD >/=30. D-MELD >/=1600 accurately predicted worse outcome in recipients with and without hepatitis C. There is significant regional variation in average D-MELD scores at transplant, however, regions with larger numbers of high D-MELD matches do not have higher survival rates. D-MELD is a simple, highly predictive tool for estimating outcomes after liver transplantation. This statistic could assist surgeons and their patients in making organ acceptance decisions. Applying D-MELD to liver allocation could eliminate many donor/recipient matches likely to have inferior outcome.