The effect of normothermic machine perfusion (NMP) on post-reperfusion hemodynamics and extrahepatic biliary duct histology of donors after cardiac death (DCD) livers after transplantation has not been addressed thoroughly and represented the object of this study. Ten livers (n=5/group) with 60’ of warm ischemia were preserved by cold storage (CS) or sanguineous NMP for 10 hours, and then reperfused for 24 hours with whole blood in an isolated perfusion system to simulate transplantation. In our experiment, arterial and portal venous flows were stable in NMP group during the entire simulated reperfusion, while decreased dramatically in CS group after 16 hours post-reperfusion (P<.05), findings consistent with severe parenchymal injury. Similarly, significant differences existed between CS and NMP group on hepatocellular enzyme release, bile volume produced, and enzyme released into bile (P<.05). On histology CS livers presented with diffuse hepatocyte congestion, necrosis, intraparenchymal hemorrhage, denudated biliary epithelium and submucosal bile duct necrosis, while NMP liver showed very mild injury in liver parenchyma and biliary architecture. Most importantly, Ki67 staining in extrahepatic bile duct showed biliary epithelial regeneration. Our findings advance the knowledge of post-reperfusion events that characterize DCD livers and propose NMP as a beneficial preservation modality able to improve biliary regeneration after a major ischemic event, which may prevent in clinical transplantation the development of ischemic cholangiopathy.

No abstract

Numerous factors impact patients’ health beyond traditional clinical characteristics. We evaluated the association of risk factors in kidney transplant patients’ communities with outcomes prior to transplantation. The primary exposure variable was a community risk score(range 0–40) derived from multiple databases and defined by factors including prevalence of comorbidities, access and quality of healthcare, self-reported physical and mental health and socioeconomic status for each US county. We merged data with the Scientific Registry of Transplant Recipients(SRTR) and utilized risk-adjusted models to evaluate effects of community risk for adult candidates listed 2004–2010(n=209,198). Patients in highest-risk communities were associated with increased mortality(Adjusted Hazard Ratio[AHR]=1.22,1.16–1.28), decreased likelihood of living donor transplantation(Adjusted Odds Ratio[AOR]=0.90,0.85–0.94), increased waitlist removal for health deterioration(AHR=1.36,1.22–1.51), decreased likelihood of preemptive-listing(AOR=0.85,0.81–0.88), increased likelihood of inactive listing(AOR=1.49,1.43–1.55) and increased likelihood of listing for expanded criteria donor kidneys(AHR=1.19,1.15–1.24). Associations persisted with adjustment for rural-urban location; furthermore the independent effects of rural-urban location were largely eliminated with adjustment for community risk. Average community risk varied widely by region and transplant center(median=21, range 5–37). Community risks are powerful factors associated with processes of care and outcomes for transplant candidates and may be important considerations for developing effective interventions and measuring quality of care of transplant centers.

The utilization of normothermic machine perfusion (NMP) may be an effective strategy to resuscitate livers from donation after circulatory death (DCD). There is no consensus regarding the efficacy of different perfusates on graft and bile duct viability. The aim of this study was to compare, in an NMP porcine DCD model, the preservation potential of three different perfusates. Twenty porcine livers with 60 min of warm ischemia were separated into four preservation groups: cold storage (CS), NMP with Steen solution (Steen; XVIVO Perfusion Inc., Denver, CO), Steen plus red blood cells (RBCs), or whole blood (WB). All livers were preserved for 10 h and reperfused to simulate transplantation for 24 h. During preservation, the NMP with Steen group presented the highest hepatocellular injury. At reperfusion, the CS group had the lowest bile production and the worst hepatocellular injury compared with all other groups, followed by NMP with Steen; the Steen plus RBC and WB groups presented the best functional and hepatocellular injury outcomes, with WB livers showing lower aspartate aminotransferase release and a trend toward better results for most parameters. Based on our results, a perfusate that contains an oxygen carrier is most effective in a model of NMP porcine DCD livers compared with Steen solution. Specifically, WB-perfused livers showed a trend toward better outcomes compared with Steen plus RBCs.

Follow-up care for living kidney donors is an important responsibility of the transplant community. Prior reports indicate incomplete donor follow-up information, which may reflect both donor and transplant center factors. New UNOS regulations require reporting of donor follow-up information by centers for 2 years. We utilized national SRTR data to evaluate donor and center-level factors associated with completed follow-up for donors 2008-2012 (n ¼ 30 026) using multivariable hierarchical logistic models. We compared center follow-up compliance based on current UNOS standards using adjusted and unadjusted models. Complete follow-up at 6, 12, and 24 months was 67%, 60%, and 50% for clinical and 51%, 40%, and 30% for laboratory data, respectively, but have improved over time. Donor risk factors for missing laboratory data included younger age 18-34

Normothermic machine perfusion (NMP) is an emerging technology to preserve liver allografts more effectively than cold storage (CS). However, little is known about the effect of NMP on steatosis and the markers indicative of hepatic quality during NMP. To address these points, we perfused 10 discarded human livers with oxygenated NMP for 24 hours after 4-6 hours of CS. All livers had a variable degree of steatosis at baseline. The perfusate consisted of packed red blood cells and fresh frozen plasma. Perfusate analysis showed an increase in triglyceride levels from the 1st hour (median, 127 mg/dL; interquartile range [IQR], 95-149 mg/dL) to 24th hour of perfusion (median, 203 mg/dL; IQR, 171-304 mg/dL; P = 0.004), but tissue steatosis did not decrease. Five livers produced a significant amount of bile (≥5 mL/hour) consistently throughout 24 hours of NMP. Lactate in the perfusate cleared to <3 mmol/L in most livers within 4-8 hours of NMP, which was independent of bile production rate. This is the first study to characterize the lipid profile and functional assessment of discarded human livers at 24 hours of NMP. Liver Transplantation 24 233-245 2018 AASLD.

Background and objectives Despite the benefits of kidney transplantation, the total number of transplants performed in the United States has stagnated since 2006. Transplant center quality metrics have been associated with a decline in transplant volume among low-performing centers. There are concerns that regulatory oversight may lead to risk aversion and lack of transplantation growth.Design, setting, participants, & measurements A retrospective cohort study of adults (age$18 years) wait-listed for kidney transplantation in the United States from 2003 to 2010 using the Scientific Registry of Transplant Recipients was conducted. The primary aim was to investigate whether measured center performance modifies the survival benefit of transplantation versus dialysis. Center performance was on the basis of the most recent Scientific Registry of Transplant Recipients evaluation at the time that patients were placed on the waiting list. The primary outcome was the time-dependent adjusted hazard ratio of death compared with remaining on the transplant waiting list.Results Among 223,808 waitlisted patients, 59,199 and 32,764 patients received a deceased or living donor transplant, respectively. Median follow-up from listing was 43 months (25th percentile=25 months, 75th percentile=67 months), and there were 43,951 total patient deaths. Deceased donor transplantation was independently associated with lower mortality at each center performance level compared with remaining on the waiting list; adjusted hazard ratio was 0.24 (95% confidence interval, 0.21 to 0.27) among 11,972 patients listed at high-performing centers, adjusted hazard ratio was 0.32 (95% confidence interval, 0.31 to 0.33) among 203,797 patients listed at centers performing as expected, and adjusted hazard ratio was 0.40 (95% confidence interval, 0.35 to 0.45) among 8039 patients listed at low-performing centers. The survival benefit was significantly different by center performance (P value for interaction ,0.001).Conclusions Findings indicate that measured center performance modifies the survival benefit of kidney transplantation, but the benefit of transplantation remains highly significant even at centers with low measured quality. Policies that concurrently emphasize improved center performance with access to transplantation should be prioritized to improve ESRD population outcomes.

No abstract