Rate of Deceased Kidney Donation From Potential In-Hospital Deaths in the US, 2003-2021.

This cross-sectional study calculates deceased kidney donation rates in the US using deaths compatible with donation as the metric's denominator.

Pretransplantation coronavirus disease 2019 vaccination requirements: A matched case-control study of factors associated with waitlist inactivation.

Numerous United States transplant centers require solid organ transplantation candidates to be vaccinated against the coronavirus disease of 2019 to be active on the United Network for Organ Sharing waiting list. This study examined characteristics of adult patients on one center's kidney transplantation waiting list whose status was inactivated due to a lack of coronavirus disease 2019 vaccination by July 1, 2022, and who did not subsequently provide proof of vaccination by August 31, 2022 (cases). Patients in the control group were retrospectively matched to patients in the case group in a 4-to-1 fashion according to age, sex, and "active" status on the waiting list. Multivariable logistic regression was performed, with race/ethnicity, primary language, health insurance, education, and Vaccine Equity Metric (VEM, a measure of health equity at the zip code level) quartile as covariates. Results revealed that patients from zip codes in the lowest VEM quartile (odds ratio [OR] 1.89; P = .02) and those insured by governmental payors (Medicare: OR, 2.00; P < .01 and Medicaid: OR, 2.89; P < .01) had higher odds of being inactivated than those from zip codes that make up the highest VEM quartile and those insured by commercial payors, respectively. These findings serve as a cautionary tale regarding universal pretransplantation vaccination requirements, which may raise equity concerns that should be considered upon policy implementation.

Living Donor Liver Transplantation for Hepatocellular Carcinoma Within and Outside Traditional Selection Criteria: A Multicentric North American Experience.

OBJECTIVE: To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. BACKGROUND: LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). METHODS: Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. RESULTS: Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. CONCLUSIONS: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

Report From a Multidisciplinary Symposium on the Future of Living Kidney Donor Transplantation.

Virtually all clinicians agree that living donor renal transplantation is the optimal treatment for permanent loss of kidney function. Yet, living donor kidney transplantation has not grown in the United States for more than 2 decades. A virtual symposium gathered experts to examine this shortcoming and to stimulate and clarify issues salient to improving living donation. The ethical principles of rewarding kidney donors and the limits of altruism as the exclusive compelling stimulus for donation were emphasized. Concepts that donor incentives could save up to 40 000 lives annually and considerable taxpayer dollars were examined, and survey data confirmed voter support for donor compensation. Objections to rewarding donors were also presented. Living donor kidney exchanges and limited numbers of deceased donor kidneys were reviewed. Discussants found consensus that attempts to increase living donation should include removing artificial barriers in donor evaluation, expansion of living donor chains, affirming the safety of live kidney donation, and assurance that donors incur no expense. If the current legal and practice standards persist, living kidney donation will fail to achieve its true potential to save lives.

Characterizing the risk of human leukocyte antigen-incompatible living donor kidney transplantation in older recipients.

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.

DCD liver transplant in patients with a MELD over 35.

Introduction: Donation after circulatory death (DCD) liver transplantation (LT) makes up well less than 1% of all LTs with a Model for End-Stage Liver Disease (MELD)≥35 in the United States. We hypothesized DCD-LT yields acceptable ischemia-reperfusion and reasonable outcomes for recipients with MELD≥35. Methods: We analyzed recipients with lab-MELD≥35 at transplant within the UCSF (n=41) and the UNOS (n=375) cohorts using multivariate Cox regression and propensity score matching. Results: In the UCSF cohort, five-year patient survival was 85% for DCD-LTs and 86% for matched-Donation after Brain Death donors-(DBD) LTs (p=0.843). Multivariate analyses showed that younger donor/recipient age and more recent transplants (2011-2021 versus 1999-2010) were associated with better survival. DCD vs. DBD graft use did not significantly impact survival (HR: 1.2, 95%CI 0.6-2.7). The transaminase peak was approximately doubled, indicating suggesting an increased ischemia-reperfusion hit. DCD-LTs had a median post-LT length of stay of 11 days, and 34% (14/41) were on dialysis at discharge versus 12 days and 22% (9/41) for DBD-LTs. 27% (11/41) DCD-LTs versus 12% (5/41) DBD-LTs developed a biliary complication (p=0.095). UNOS cohort analysis confirmed patient survival predictors, but DCD graft emerged as a risk factor (HR: 1.5, 95%CI 1.3-1.9) with five-year patient survival of 65% versus 75% for DBD-LTs (p=0.016). This difference became non-significant in a sub-analysis focusing on MELD 35-36 recipients. Analysis of MELD≥35 DCD recipients showed that donor age of <30yo independently reduced the risk of graft loss by 30% (HR, 95%CI: 0.7 (0.9-0.5), p=0.019). Retransplant status was associated with a doubled risk of adverse event (HR, 95%CI: 2.1 (1.4-3.3), p=0.001). The rejection rates at 1y were similar between DCD- and DBD-LTs, (9.3% (35/375) versus 1,541 (8.7% (1,541/17,677), respectively). Discussion: In highly selected recipient/donor pair, DCD transplantation is feasible and can achieve comparable survival to DBD transplantation. Biliary complications occurred at the expected rates. In the absence of selection, DCD-LTs outcomes remain worse than those of DBD-LTs.

Real-world implementation of normothermic machine perfusion: A detailed analysis of intraoperative and early postoperative impact.

BACKGROUND: Outcome data for the great majority of liver normothermic machine perfusion (NMP) cases derive from the strict confines of clinical trials. Detailed specifics regarding the intraoperative and early postoperative impact of NMP on reperfusion injury and its sequelae during real-world use of this emerging technology remain largely unavailable. METHODS: We analyzed transplants performed in a 3-month pilot period during which surgeons invoked commercial NMP at their discretion. Living donor, multi-organ, and hypothermic machine perfusion transplants were excluded. RESULTS: Intraoperatively, NMP (n = 24) compared to static cold storage (n = 25) recipients required less peri-reperfusion bolus epinephrine (0 vs. 60 µg; p < .001) and post-reperfusion fresh frozen plasma (2.5 vs. 7.0 units; p = .0069), platelets (.0 vs. 2.0 units; p = .042), and hemostatic agents (0% vs. 24%; p = .010). Time from incision to venous reperfusion did not differ (3.6 vs. 3.1; p = .095) but time from venous reperfusion to surgery end was shorter for NMP recipients (2.3 vs. 2.8 h; p = .0045). Postoperatively, NMP recipients required fewer red blood cell (1.0 vs. 4.0 units; p = .0083) and fresh frozen plasma (4.0 vs. 7.0 units; p = .046) transfusions, had shorter intensive care unit stays (33.5 vs. 58.4 h; p = .012), and experienced less early allograft dysfunction according to both the Model for Early Allograft Function Score (3.4 vs. 5.0; p = .0047) and peak AST within 10 days of transplant (619 vs. 1,181 U/L; p = .036). Liver acceptance for the corresponding recipient was conditional on NMP use for 63% (15/24) of cases. CONCLUSION: Real-world NMP use was associated with significantly lower intensity of reperfusion injury and intraoperative and postoperative care that may translate into patient benefit.

Steroid Avoidance After Adult Living Donor Liver Transplant: A Cohort Analysis.

Although steroid avoidance (SA) has been studied in deceased donor liver transplant, little is known about SA in living donor liver transplant (LDLT). We report the characteristics and outcomes, including the incidence of early acute rejection (AR) and complications of steroid use, in 2 cohorts of LDLT recipients. Methods: Routine steroid maintenance (SM) after LDLT was stopped in December 2017. Our single-center retrospective cohort study spans 2 eras. Two hundred forty-two adult recipients underwent LDLT with SM (January 2000-December 2017), and 83 adult recipients (December 2017-August 2021) underwent LDLT with SA. Early AR was defined as a biopsy showing pathologic characteristics within 6 mo after LDLT. Univariate and multivariate logistic regressions were performed to evaluate the effects of relevant recipient and donor characteristics on the incidence of early AR in our cohort. Results: Neither the difference in early AR rate between cohorts (SA 19/83 [22.9%] versus SM 41/242 [17%]; P = 0.46) nor a subset analysis of patients with autoimmune disease (SA 5/17 [29.4%] versus SM 19/58 [22.4%]; P = 0.71) reached statistical significance. Univariate and multivariate logistic regressions for early AR identified recipient age to be a statistically significant risk factor (P < 0.001). Of the patients without diabetes before LDLT, 3 of 56 (5.4%) on SA versus 26 of 200 (13%) on SM needed medications prescribed for glucose control at the time of discharge (P = 0.11). Patient survival was similar between SA and SM cohorts (SA 94% versus SM 91%, P = 0.34) 3 y after transplant. Conclusions: LDLT recipients treated with SA do not exhibit significantly higher rates of rejection or increased mortality than patients treated with SM. Notably, this result is similar for recipients with autoimmune disease.

Living donor liver transplant candidate and donor selection and engagement: Meeting report from the living donor liver transplant consensus conference.

INTRODUCTION: Living donor liver transplantation (LDLT) is a promising option for mitigating the deceased donor organ shortage and reducing waitlist mortality. Despite excellent outcomes and data supporting expanding candidate indications for LDLT, broader uptake throughout the United States has yet to occur. METHODS: In response to this, the American Society of Transplantation hosted a virtual consensus conference (October 18-19, 2021), bringing together relevant experts with the aim of identifying barriers to broader implementation and making recommendations regarding strategies to address these barriers. In this report, we summarize the findings relevant to the selection and engagement of both the LDLT candidate and living donor. Utilizing a modified Delphi approach, barrier and strategy statements were developed, refined, and voted on for overall barrier importance and potential impact and feasibility of the strategy to address said barrier. RESULTS: Barriers identified fell into three general categories: 1) awareness, acceptance, and engagement across patients (potential candidates and donors), providers, and institutions, 2) data gaps and lack of standardization in candidate and donor selection, and 3) data gaps regarding post-living liver donation outcomes and resource needs. CONCLUSIONS: Strategies to address barriers included efforts toward education and engagement across populations, rigorous and collaborative research, and institutional commitment and resources.

Nodular Regenerative Hyperplasia After Liver Transplant; It's All in the Presentation.

There is a paucity of data on nodular regenerative hyperplasia after liver transplant. We aim to define the clinical disease trajectory and identify predictors of outcome for this rare diagnosis. This is a retrospective review of postulated risk factors and outcome in patients with nodular regenerative hyperplasia. Patients were classified as having a late presentation if nodular regenerative hyperplasia was diagnosed > 48 months from transplant, and symptomatic if portal hypertensive symptoms were present. Forty-nine of 3,711 (1.3%) adult recipients developed nodular regenerative hyperplasia, and mortality was 32.7% with an average follow up of 84.6 months. The MELD-Na 6 months after diagnosis did not change significantly. Patients with symptomatic portal hypertension at the time of diagnosis had a significantly higher risk of mortality (51.8%) compared to patients with liver test abnormalities alone (10.5%). 44.9% of patients had no previously postulated risk factor. Anastomotic vascular complications do not appear to be the etiology in most patients. The results suggest the vast majority of patients presenting with liver test abnormalities alone have stable disease and excellent long term survival, in contrast to the 56.3% mortality seen in patients that present more than 48 months after LT with symptomatic portal hypertension at diagnosis.

Projecting the Economic Impact of Compensating Living Kidney Donors in the United States: Cost-Benefit Analysis Demonstrates Substantial Patient and Societal Gains.

OBJECTIVES: The aim of this study was to show how the US government could save approximately 47 000 patients with chronic kidney failure each year from suffering on dialysis and premature death by compensating living kidney donors enough to completely end the kidney shortage. METHODS: Supply and demand analysis was used to estimate the number of donated kidneys needed to end the kidney shortage and the level of compensation required to encourage this number of donations. These results were then input into a detailed cost-benefit analysis to estimate the economic value of kidney transplantation to (1) the average kidney recipient and their caregiver, (2) taxpayers, and (3) society in general. RESULTS: We estimate half of patients diagnosed with kidney failure each year-approximately 62 000 patients-could be saved from suffering on dialysis and premature death if they could receive an average of 1½ kidney transplants. However, currently there are only enough donated kidneys to save approximately 15 000 patients. To encourage sufficient donations to save the other 47 000 patients, the government would have to compensate living kidney donors approximately $77 000 (±50%) per donor. The value of transplantation to an average kidney recipient (and caregiver) would be approximately $1.5 million, and the savings from the recipient not needing expensive dialysis treatments would be approximately $1.2 million. CONCLUSIONS: This analysis reveals the huge benefit that compensating living kidney donors would provide to patients with kidney failure and their caregivers and, conversely, the huge cost that is being imposed on these patients and their families by the current legal prohibition against such compensation.

Influence of surgical technique in donor hepatectomy on immediate and short-term living donor outcomes - A systematic review of the literature, meta-analysis, and expert panel recommendations.

BACKGROUND: There are currently no guidelines pertaining to ERAS pathways in living donor hepatectomy. OBJECTIVES: The aim of this study was to identify whether surgical technique influences immediate and short-term outcomes after living liver donation surgery. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review and meta-analysis following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel (CRD42021260707). Endpoints were mortality, overall complications, serious complications, bile eaks, pulmonary complications, estimated blood loss and length of stay. RESULTS: Of the 2410 screened articles, 21 articles were included for final analysis; three observational, 13 retrospective cohort, four prospective cohort studies, and one randomized trial. Overall complications were higher with right versus left hepatectomy (26.8% vs. 20.8%; OR 1.4, P = .010). Donors after left hepatectomy had shorter length of stay (MD 1.4 days) compared to right hepatectomy. There was no difference in outcomes after right donor hepatectomy with versus without middle hepatic vein. We had limited data on the influence of incision type and minimally invasive approaches on living donor outcomes, and no data on the effect of operative time on donor outcomes. CONCLUSIONS: Left donor hepatectomy should be preferred over right hepatectomy, as it is related to improved donor short-term outcomes (QOE; Moderate | Grade of Recommendation; Strong). Right donor hepatectomy with or without MHV has equivalent outcomes (QOE; Moderate | Grade of Recommendation; Strong); no preference is recommended, decision should be based on program's experience and expertise. No difference in outcomes was observed related to incision type, minimally invasive vs. open (QOE; Low | Grade of Recommendation; Weak); no preference can be recommended.

Prefusion F Protein-Based Respiratory Syncytial Virus Immunization in Pregnancy.

BACKGROUND: Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain. METHODS: In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 µg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios. RESULTS: This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios. CONCLUSIONS: RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; ClinicalTrials.gov number, NCT04032093.).

Trends in Cost Attributable to Kidney Transplantation Evaluation and Waiting List Management in the United States, 2012-2017.

Importance: While recent policy reforms aim to improve access to kidney transplantation for patients with end-stage kidney disease, the cost implications of kidney waiting list expansion are not well understood. The Organ Acquisition Cost Center (OACC) is the mechanism by which Medicare reimburses kidney transplantation programs, at cost, for costs attributable to kidney transplantation evaluation and waiting list management, but these costs have not been well described to date. Objectives: To describe temporal trends in mean OACC costs per kidney transplantation and to identify factors most associated with cost. Design, Setting, and Participants: This economic evaluation included all kidney transplantation waiting list candidates and recipients in the United States from 2012 to 2017. A population-based study of cost center reports was conducted using data from all Center of Medicare & Medicaid-certified transplantation hospitals. Data analysis was conducted from June to August 2021. Exposures: Year, local price index, transplantation and waiting list volume of transplantation program, and comorbidity burden. Main Outcomes and Measures: Mean OACC costs per kidney transplantation. Results: In 1335 hospital-years from 2012 through 2017, Medicare's share of OACC costs increased from $0.95 billion in 2012 to $1.32 billion in 2017 (3.7% of total Medicare End-Stage Renal Disease program expenditure). Median (IQR) OACC costs per transplantation increased from $81 000 ($66 000 to $103 000) in 2012 to $100 000 ($82 000 to $125 000) in 2017. Kidney organ procurement costs contributed to 36% of mean OACC costs per transplantation throughout the study period. During the study period, transplantation hospitals experienced increases in kidney waiting list volume, kidney waiting list active volume, kidney transplantation volume, and comorbidity burden. For a median-sized transplantation program, mean OACC costs per transplantation decreased with more transplants (-$3500 [95% CI, -$4300 to -$2700] per 10 transplants; P < .001) and increased with year ($4400 [95% CI, $3500 to $5300] per year; P < .001), local price index ($1900 [95% CI, $200 to $3700] per 10-point increase; P = .03), patients listed active on the waiting list ($3100 [95% CI, $1700 to $4600] per 100 patients; P < .001), and patients on the waiting list with high comorbidities ($1500 [9% CI, $600 to $2500] per 1% increase in proportion of waitlisted patients with the highest comorbidity score; P = .002). Conclusions and Relevance: In this study, OACC costs increased at 4% per year from 2012 to 2017 and were not solely attributable to the cost of organ procurement. Expanding the waiting list will likely contribute to further increases in the mean OACC costs per transplantation and substantially increase Medicare liability.

Assessment of long-term outcomes post living liver donation highlights the importance of scientific integrity when presenting transplant registry data.

Living donor liver transplantation has expanded in recent years, particularly in North America. As experience with this procedure has matured over the last 25 years, centers are increasingly faced with potential living donors who are more medically complex. As donors move through the evaluation process, completing the informed consent process continues to be challenged by a paucity of granular data demonstrating long-term outcomes and overall safety specifically in the otherwise "healthy" living liver donor population. Two recently published studies examined long-term outcomes post-living liver donation using Korean registry data and reported similar results, with excellent overall survival when compared to appropriately matched controls. However, the authors of these studies were presented differently, with one reporting an alarmist view based on one aspect of a suboptimal analysis approach using an inappropriate comparator group. Herein, the North American Living Liver Donor Innovation Group (NALLDIG) consortium discusses these two studies and their potential impact on living liver donation in North America, ultimately highlighting the importance of scientific integrity in data presentation and dissemination when using transplant registry data.

Consent to organ offers from public health service "Increased Risk" donors decreases time to transplant and waitlist mortality.

BACKGROUND: The Public Health Service Increased Risk designation identified organ donors at increased risk of transmitting hepatitis B, hepatitis C, and human immunodeficiency virus. Despite clear data demonstrating a low absolute risk of disease transmission from these donors, patients are hesitant to consent to receiving organs from these donors. We hypothesize that patients who consent to receiving offers from these donors have decreased time to transplant and decreased waitlist mortality. METHODS: We performed a single-center retrospective review of all-comers waitlisted for liver transplant from 2013 to 2019. The three competing risk events (transplant, death, and removal from transplant list) were analyzed. 1603 patients were included, of which 1244 (77.6%) consented to offers from increased risk donors. RESULTS: Compared to those who did not consent, those who did had 2.3 times the rate of transplant (SHR 2.29, 95% CI 1.88-2.79, p < 0.0001), with a median time to transplant of 11 months versus 14 months (p < 0.0001), as well as a 44% decrease in the rate of death on the waitlist (SHR 0.56, 95% CI 0.42-0.74, p < 0.0001). All findings remained significant after controlling for the recipient age, race, gender, blood type, and MELD. Of those who did not consent, 63/359 (17.5%) received a transplant, all of which were from standard criteria donors, and of those who did consent, 615/1244 (49.4%) received a transplant, of which 183/615 (29.8%) were from increased risk donors. CONCLUSIONS: The findings of decreased rates of transplantation and increased risk of death on the waiting list by patients who were unwilling to accept risks of viral transmission of 1/300-1/1000 in the worst case scenarios suggests that this consent process may be harmful especially when involving "trigger" words such as HIV. The rigor of the consent process for the use of these organs was recently changed but a broader discussion about informed consent in similar situations is important.