Trends in utilization of deceased donor kidneys based on hepatitis C virus status and impact of public health service labeling on discard

BackgroundKidneys from deceased donors infected with hepatitis C virus (HCV) are underutilized. Most HCV virus‐infected donors are designated as Public Health Service increased donors (PHS‐IR). Impact of PHS and HCV designations on discard is not well studied.MethodsWe queried the UNOS data set for all deceased donor kidneys between January 2015 and December 2018. The final study cohort donors (n = 38 702) were stratified into three groups based on HCV antibody (Ab) and NAT status: (a) Ab−/NAT− (n = 35 861); (b) Ab+/NAT− (n = 973); and (c) Ab±/NAT+ (n = 1868). We analyzed utilization/discard rates of these organs, the impact of PHS‐IR and HCV designations on discard using multivariable two‐level hierarchical logistic regression models, forecasted number of HCV viremic donors/kidneys by 2023.ResultsDuring the study period, (a) the number of viremic donor kidneys increased 2 folds; (b) the multilevel mixed‐effects logistic regression models showed that, overall, the PHS labeling (OR 1.20, CI 95% CI 1.15‐1.29) and HCV designation (OR 2.29; 95% CI 2.15‐2.43) were independently associated with increased risk of discard; (c) contrary to the general perception, PHS‐IR kidneys across all HCV groups, compared to PHS‐IR kidneys were more likely to be discarded; (d) we forecasted that the number of kidneys from HCV viremic donor kidneys might increase from 1376 in 2019 to 2092 in 2023.ConclusionHepatitis C virus viremic kidneys might represent 10%‐15% of deceased donor organ pool soon with the current rate of the opioid epidemic. PHS labeling effect on discard requires further discussion of the utility of this classification.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154409/1/tid13204_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154409/2/tid13204.pd

Simultaneous Liver-Kidney Transplantation in Liver Transplant Candidates With Renal Dysfunction: Importance of Creatinine Levels, Dialysis, and Organ Quality in Survival

IntroductionThe survival benefit from simultaneous liver-kidney transplantation (SLK) over liver transplant alone (LTA) in recipients with moderate renal dysfunction is not well understood. Moreover, the impact of deceased donor organ quality in SLK survival has not been well described in the literature.MethodsThe Scientific Registry of Transplant Recipients was studied for adult recipients receiving LTA (N = 2700) or SLK (N = 1361) with moderate renal insufficiency between 2003 and 2013. The study cohort was stratified into 4 groups based on serum creatinine (<2 mg/dl versus ≥2 mg/dl) and dialysis status at listing and transplant. The patients with end-stage renal disease and requiring acute dialysis more than 3 months before transplantation were excluded. A propensity score matching was performed in each stratified group to factor out imbalances between the SLK and LTA regarding covariate distribution and to reduce measured confounding. Donor quality was assessed with liver donor risk index. The primary outcome of interest was posttransplant mortality.ResultsIn multivariable propensity score-matched Cox proportional hazard models, SLK led to decrease in posttransplant mortality compared with LTA across all 4 groups, but only reached statistical significance (hazard ratio 0.77; 95% confidence interval, 0.62–0.96) in the recipients not exposed to dialysis and serum creatinine ≥ 2 mg/dl at transplant (mortality incidence rate per patient-year 5.7% in SLK vs. 7.6% in LTA, P = 0.005). The decrease in mortality was observed among SLK recipients with better quality donors (liver donor risk index < 1.5).DiscussionExposure to pretransplantation dialysis and donor quality affected overall survival among SLK recipients

Platelet depletion in mice increases mortality after thermal injury

Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in innate and adaptive immunity. However, the role of platelets in the immune response to injury remains undefined. We tested the importance of platelets in the host response to serious injury in a newly developed platelet-deficient mouse model. Wild-type and platelet-depleted C57BL/6J mice underwent a 25% full-thickness total body surface area thermal or sham injury. Platelet-deficient mice showed survival of 51% at 48 hours after injury compared with 94% to 100% survival in experimental control mice (P < .001). Necropsy and histology ruled out hemorrhage and hypovolemia as causes of death. Percentages of peripheral blood monocytes (P < .01) and neutrophils (P < .05) were increased between 36 and 48 hours after thermal injury in platelet-deficient mice compared with control mice. Plasma levels of TNFα (P < .001), IL-6 (P < .001), and MCP-1 (P < .05) were also elevated by 24 hours whereas levels of TGFβ1 were reduced between 24 and 36 hours following injury in platelet-depleted mice (P < .001) compared with control mice. Our findings demonstrate for the first time that platelets play a critical protective role during the host response to injury. Moreover, our findings suggest that platelets and, more importantly, platelet-derived TGFβ1 modulate the systemic inflammatory response occurring after injury

Effect of donor HSD17B13 genotype on patient survival after liver transplant: a retrospective cohort studyResearch in context

Summary: Background: Several genetic variants are associated with chronic liver disease. The role of these variants in outcomes after liver transplantation (LT) is uncertain. The aim of this study was to determine if donor genotype at risk-associated variants in PNPLA3 (rs738409 C>G, p.I148M) and HSD17B13 (rs72613567 T>TA; rs80182459, p.A192Lfs∗8) influences post-LT survival. Methods: In this retrospective cohort study, data on 2346 adults who underwent first-time LT between January 1, 1999 and June 30, 2020 and who had donor DNA samples available at five large Transplant Immunology Laboratories in Texas, USA, were obtained from the United Network for Organ Sharing (UNOS). Duplicates, patients with insufficient donor DNA for genotyping, those who were <18 years of age at the time of transplant, had had a previous transplant or had missing genotype data were excluded. The primary outcomes were patient and graft survival after LT. The association between donor genotype and post-LT survival was examined using Kaplan–Meier method and multivariable-adjusted Cox proportional hazards models. Findings: Median age of LT recipients was 57 [interquartile range (IQR), 50–62] years; 837 (35.7%) were women; 1362 (58.1%) White, 713 (30.4%) Hispanic, 182 (7.8%) Black/African-American. Median follow-up time was 3.95 years. Post-LT survival was not affected by donor PNPLA3 genotype but was significantly reduced among recipients of livers with two HSD17B13 loss-of-function (LoF) variants compared to those receiving livers with no HSD17B13 LoF alleles (unadjusted one-year survival: 82.6% vs 93.9%, P < 0.0001; five-year survival: 73.1% vs 82.9%, P = 0.0017; adjusted hazard ratio [HR], 2.25; 95% CI, 1.61–3.15 after adjustment for recipient age, sex, and self-reported ethnicity). Excess mortality was restricted to those receiving steroid induction immunosuppression (crude 90-day post-LT mortality, 9.3% [95% CI, 1.9%–16.1%] vs 1.9% [95% CI, 0.9%–2.9%] in recipients of livers with two vs no HSD17B13 LoF alleles, P = 0.0012; age, sex, and ethnicity-adjusted HR, 2.85; 95% CI, 1.72–4.71, P < 0.0001). No reduction was seen among patients who did not receive steroid induction (90-day mortality 3.1% [95% CI, 0%–7.3%] vs 2% [95% CI, 0.9%–3.1%], P = 0.65; adjusted HR, 1.17; 95% CI, 0.66–2.08, P = 0.60). Interpretation: Donor HSD17B13 genotype adversely affects post-LT survival in patients receiving steroid induction. Additional studies are required to confirm this association. Funding: The National Institutes of Health and American Society of Transplant Surgeons Collaborative Scientist Gran