Deceased-donor Transplantation Research Articles

Pediatric Nephrology Workforce and Access of Children with Kidney Failure to Transplantation in the United States.

Nephrology is one of the pediatric subspecialties with the largest workforce shortage in the US. Waitlist registration is one of the first steps towards kidney transplantation and is facilitated by pediatric nephrologists. The objective of this study was to determine whether state-level density of pediatric nephrologists is associated with access to waitlisting (primary outcome) or kidney transplantation (secondary outcome) in children with kidney failure. Using Cox proportional hazards and logistic regression analyses, we studied children <18 years who developed kidney failure between 2016-2020 according to the US Renal Data System, the national kidney failure registry. The density of pediatric nephrologists (determined by the count of pediatric nephrologists per 100,000 children in each state) was estimated using workforce data from the American Board of Pediatrics and categorized into three groups: > 1, 0.5-1, and <0.5. We included 4,497 children, of whom 3,198 (71%) were waitlisted and 2,691 (60%) received transplantation. Children residing in states with pediatric nephrologist density >1 had 33% (HR 1.33; 95%CI 1.07-1.66) and 22% (HR 1.22; 95%CI 1.02-1.45) better access to waitlisting compared to those residing in states with <0.5 pediatric nephrologist density (reference group) in unadjusted and adjusted analysis, respectively. Pediatric nephrologist density was particularly important for the odds of preemptive waitlisting (adjusted OR 1.56; 95% CI 1.02-2.41). The adjusted HR was 1.25 (95% CI 1.00-1.55, p=0.046) for deceased donor transplantation and 1.24 (95% CI 0.85-1.82) for living donor transplantation for children residing in states with pediatric nephrologist density > 1 compared to the reference group. Children residing in states with higher pediatric nephrologist density had better access to waitlist registration, especially preemptively, and deceased donor transplantation.

Expanding Opportunities for Living Donation: Recommendations From the 2023 Santander Summit to Ensure Donor Protections, Informed Decision Making, and Equitable Access.

A strategic vision toward global convergence in transplantation must encourage and remove barriers to living organ donation and transplantation. Here, we discuss deliberations of a working group of the 2023 Santander Summit charged with formulating recommendations for the safe expansion of living donor kidney transplantation and living donor liver transplantation worldwide. Living donor kidney transplantation has grown to be the preferred treatment for advanced kidney failure. Living donor liver transplantation emerged more recently as a strategy to reduce waitlist mortality, with adoption influenced by cultural factors, regional policies, clinical team experience, and the maturity of regional deceased donor transplant systems. Barriers to living donor transplantation span domains of education, infrastructure, risk assessment/risk communication, and financial burden to donors. Paired donor exchange is a growing option for overcoming incompatibilities to transplantation but is variably used across and within countries. Effectively expanding access to living donor transplantation requires multifaceted strategies, including improved education and outreach, and measures to enhance efficiency, transparency, and shared decision making in donor candidate evaluation. Efforts toward global dissemination and vigilant oversight of best practices and international standards for the assessment, informed consent, approval, and monitoring of living donors are needed. Fostering greater participation in paired exchange requires eliminating disincentives and logistical obstacles for transplant programs and patients, and establishing an ethical and legal framework grounded in World Health Organization Guiding Principles. Sharing of best practices from successful countries and programs to jurisdictions with emerging practices is vital to safely expand the practice of living donation worldwide and bring the field together globally.

Differences in chronic lung allograft dysfunction between deceased-donor lung transplantation and living-donor lobar lung transplantation

ObjectiveTo explore the characteristics and prognostic impact of chronic lung allograft dysfunction (CLAD) after deceased-donor lung transplantation and living-donor lobar lung transplantation, wherein the lower lobes from 2 donors are usually transplanted into one recipient. MethodsThe clinical data of 123 deceased-donor and 67 living-donor lung transplantations performed in adult patients at our institution between June 2008 and September 2019 were retrospectively reviewed. The cumulative incidence of CLAD was evaluated on a per-recipient and per-donor graft basis using the Kaplan-Meier method. ResultsA smaller number of human leukocyte antigen mismatches, shorter ischemic time, and lower incidence of grade 3 primary graft dysfunction were observed in living-donor transplantation than in deceased-donor transplantation (P < .001). Restrictive allograft syndrome−type CLAD occurred in 9 (20.9%) of 43 patients with CLAD after deceased-donor transplantation and 9 (45.0%) of 20 patients with CLAD after living-donor transplantation. CLAD occurred unilaterally in 15 patients (75.0%) after bilateral living-donor transplantation. Despite the greater incidence of restrictive allograft syndrome−type CLAD after living-donor transplantation, the overall survival rates after the transplantation and survival rates after the onset of CLAD were comparable between the patients receiving deceased-donor transplants and living-donor transplants. The cumulative incidence of CLAD per recipient was similar between recipients of deceased-donor and the living-donor transplants (P = .32). In the per-donor graft analysis, the cumulative incidence of CLAD was significantly lower in the living-donor grafts than in the deceased-donor grafts (P = .003). ConclusionsThe manifestation of CLAD after living-donor lobar lung transplantation is unique and differs from that after deceased-donor lung transplantation.

The OPTN Expeditious Task Force: Improved Organ Utilization and Efficiency to Drive Transformational Growth in Solid Organ Transplant in the United States

The Organ Procurment and Transplant Network (OPTN) Expeditious Task Force (ETF) was conceived and initiated in response to a need to move quickly to greatly expand successful deceased-donor transplant across the U.S. The ETF, using data from the top 20% of transplant programs ranked by ability to manage successful growth in transplant volume, came up with a bold aim of facilitating 60,000 successful transplants by 2026 to save more lives. In order to achieve this transformational growth, the ETF will use a data-driven approach, partnering with key stakeholders across the transplant system to secure commitments, reduce barriers, obtain data, align metrics, evaluate new technologies, and run short trials that will better inform future policy developments. To achieve this growth, the two primary aims of the ETF are increasing system efficiency and improving organ and donor utilization. The initial ETF workstreams will focus on 6 areas that include assessments of organ non-utilization (where donors are consented but organs not recovered) and non-use (where organs are recovered but not transplanted), facilitating community events to address challenges in utilization and efficiency; hosting transplant growth collaboratives focused on securing resources needed for transformational growth; creating tools for patient empowerment; evaluating OPTN policies to remove barriers; and designing short trials of rescue pathways for organs at risk for non-use.

Deceased donor urinary Dickkopf-3 associates with future allograft function following kidney transplantation

Predicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function. We measured uDKK3/crea ratios (uDKK3/crea) from 95 deceased and 46 living kidney donors. Prenephrectomy uDKK3/crea levels were 100× higher in deceased than in living donors (9888 pg/mg vs 113 pg/mg; P < .001). Among deceased donor transplantations, recipients were stratified by their corresponding uDKK3/crea donor levels ranging below (group A, n = 68) or above (group B, n = 65) median. The primary end point of best estimated glomerular filtration rate (eGFR) within the first 3 months after kidney transplantation was superior in group A (56.3 mL/min/1.73 m2) than that in group B (44.2 mL/min/1.73 m2; P = .0139). Second, the composite clinical end point consisting of death, allograft failure or eGFR decline >50% occurred less frequent in group A. By mixed linear regression modeling, donor uDKK3/crea remained an independent predictor of eGFR after transplantation, with a slope of −4.282 mL/min/1.73 m2 per logarithmic increase in donor uDKK3/crea. In summary, uDKK3 may serve as a noninvasive, donor-dependent biomarker for assessing organ quality and future allograft function.

P.281: When two may be better than one; a tale of two extremes in kidney transplant. Initial report from a ‘new’ deceased donor transplant programme in the United Arab Emirates.

P.281: When two may be better than one; a tale of two extremes in kidney transplant. Initial report from a ‘new’ deceased donor transplant programme in the United Arab Emirates.

P.476: Virtual Crossmatch alone for deceased donor transplantation: Single centre experience from India.

P.476: Virtual Crossmatch alone for deceased donor transplantation: Single centre experience from India.

Highly Sensitized Kidney Transplant Outcomes After the 2014 Kidney Allocation System Change.

Introduction: Kidney Allocation System (KAS) was implemented by United Network for Organ Sharing in 2014 to reduce allocation disparities. Research Questions: Outcomes of highly sensitized patients (calculated panel reactive antibody (cPRA) ≥ 97%) before and after KAS were compared to low-risk recipients (cPRA <10%) in the post-KAS era were examined. The impact on racial disparities was determined. Design: This was a retrospective study of national registry data. Two cohorts of adult candidates waitlisted for deceased donor transplantation during 3-year periods before and after KAS were identified. Results: Highly sensitized patients (N = 1238 and 4687) received a deceased donor kidney transplant between January 1, 2011 and December 31, 2013 and between January 1, 2015 and December, 31, 2017. Racial disparity for highly sensitized patients improved, yet remained significant (P < 0.001), with Black patients comprising 40% and 41% of the highly sensitized candidates and 28% and 34% of the recipients pre- and post-KAS. While posttransplant death-censored graft failure for highly sensitized recipients was similar overall, post-KAS was associated with improved graft survival in the first year after transplant (HR 0.56, 95% CI 0.40-0.78). When compared to contemporaneous lowrisk recipients, both death-censored and all-cause graft failure were similar for highly sensitized recipients and was associated with increased risk for death-censored graft failure beyond the first year (HR 1.39, 95% CI 1.11-1.73). Conclusion: The allocation system led to an increase in transplantation in highly sensitized candidates without compromising outcomes. Although KAS has led to more balanced transplant rates between highly sensitized Black and White patients, racial inequalities persist.

V-110.4: Assessing the outcome of deceased donor transplantation in recipients aged 70 and above: Are renal transplants a viable option for the ageing population?

V-110.4: Assessing the outcome of deceased donor transplantation in recipients aged 70 and above: Are renal transplants a viable option for the ageing population?

The Association between Residential Segregation and Access to Kidney Transplantation: Evidence from a Multistate Cohort Study.

Individuals currently living in neighborhoods historically influenced by racial segregation have reduced access to healthcare. Whether this is true for individuals with end-stage kidney disease (ESKD) seeking transplant is unknown. We identified Black or White adults (n = 42,401; 18-80 years) with ESKD initiating kidney replacement therapy (KRT) in three US States (Georgia, North Carolina, South Carolina) between January 2015 and December 2019, with follow-up through 2020, from the United States Renal Data System (USRDS). Residential segregation was defined using the racial Index of Concentration at the Extremes and classified into tertiles (predominantly Black, mixed, or predominantly White neighborhoods). Primary outcomes were referral within 12-months of KRT initiation (among patients initiating KRT) and evaluation within six-months of referral (among all referred patients), determined via linkage of USRDS to the Early-Steps to Transplant Access Registry. Secondary outcomes included waitlisting (among evaluated patients), and living or deceased donor transplant (among waitlisted patients). The association between residential segregation and each outcome was assessed using multivariable Cox models with robust sandwich variance estimators. In models adjusted for clinical factors, individuals living in predominantly Black or mixed (vs. predominantly White) neighborhoods were 8% (adjusted hazard ratio (aHR) 0.92 [0.88 - 0.96]) and 5% (aHR: 0.95 [0.91 - 0.99]) less likely to be referred for a kidney transplant, 18% (aHR: 0.82 [0.76 - 0.90]) and 9% (aHR: 0.91 [0.84 - 0.98]) less likely to be waitlisted among those who started evaluation, and 54% (aHR: 0.46 [0.36 - 0.58]) and 24% (aHR: 0.76 [0.63 - 0.93]) less likely to receive a living donor kidney transplant among those who were waitlisted, respectively. For other transplant steps, associations were non-significant. Individuals with ESKD living in historically and currently marginalized communities in the Southeast US have reduced access to important steps along the transplant care continuum.

Majority Rules? Assessing Access to Kidney Transplantation in a Predominantly Hispanic Population.

Despite being the national's largest ethnic minority, Hispanic Americans have inferior kidney transplant opportunities. San Antonio, Texas is the largest US city with a majority Hispanic population. We assessed the impact of this unique ethnic milieu on waitlisting and transplant practices among Hispanic patients. We studied patients >18 years old listed at our center for a kidney-only transplant between 2003-2022. Timing of waitlisting, transplant rates and waitlist outcomes were compared between Hispanic and non-Hispanic White patients. We evaluated 11,895 patients, of whom 67% (n = 8,008) were Hispanic, and 20% (n = 2,341) were White. Preemptive listing was less frequent in Hispanic patients (18% vs 37%). One-third of listed Hispanic patients (37%) and half of White patients (50%) were transplanted, with living-donor kidney transplant performed in 59% (n = 1,755) and 77% (n = 898), respectively. Adjusting for age, sex, blood type, preemptive listing, immunologic sensitization, education, employment, and listing era, Hispanic patients remained less likely to receive a deceased-donor transplant (HR 0.82, 95% CI 0.71 - 0.95). On covariate adjustment, White patients were more likely to experience waitlist death or deterioration (HR 1.23, 95% CI 1.12 - 1.36). Although waitlist attrition was more favorable among Hispanic patients, waitlist registration was delayed and kidney transplants less frequent compared to White patients. These data demonstrate that majority status alone does not mitigate ethnic disparities in kidney transplantation, while underlining the critical need for ongoing efforts to address physician and patient attitudes relating to suitability of Hispanic patients for transplantation.

Revolutionizing deceased donor transplantation: How new approaches to machine perfusion broadens the horizon for organ donation

Solid organ transplantation is lifesaving for persons with end-stage organ disease. Thanks to advancements in organ preservation, surgeons are now able to successfully transplant organs that were previously considered high risk for poor graft function. Innovations in perfusion machine types, preservation solutions and additives to preservation solutions have significantly improved the ability to utilize organs previously thought unusable.Newer organ preservation techniques are offering a promising outlook for extending graft longevity and improving transplant outcomes. This review explores the impact of deceased donor type on graft quality and highlights emerging strategies designed to improve the function and viability of deceased donor organs.

Baseline lung allograft dysfunction after bilateral deceased-donor lung transplantation: A single-center experience in Japan

BackgroundBaseline lung allograft dysfunction (BLAD) refers to a condition in which a lung transplant recipient does not achieve normal pulmonary function (i.e., forced expiratory volume in 1 s or forced vital capacity of <80% of predicted values). Although BLAD is reportedly associated with a poor prognosis, the condition has not been examined in Japanese patients. MethodsIn this study, we retrospectively examined 38 Japanese adults who underwent bilateral lung transplantation from 2015 to 2022 in a single center. ResultsTwenty-one (55%) patients met the criteria for BLAD. No significant differences were found in recipient or donor factors between the BLAD and non-BLAD groups, but the donor–recipient ratio of the predicted vital capacity was lower in the BLAD group (p = 0.009). The intensive care unit length of stay, ventilator duration, and blood loss during transplant surgery were significantly higher in the BLAD group (p < 0.05). No significant difference was found in survival. The median observation period was significantly shorter in the BLAD than non-BLAD group (744 vs.1192 days, respectively; p = 0.031). The time to reach the normal threshold of pulmonary function after lung transplantation varied among the patients, ranging from 6 months to 4 years. ConclusionsThe characteristics of these Japanese patients with BLAD were similar to those of other patients in previous reports. The effects of the observation period and donor–recipient age discrepancy on BLAD require further exploration.

Histopathology of Allograft Nephrectomies - A Ten Year Observational Study.

Though infrequent, allograft nephrectomies are performed for early and late graft loss. The study aims to analyze the histopathologic characteristics of allograft nephrectomy specimens. We conducted an observational study of 103 cases of allograft nephrectomies from 21 centers from 2013 to 2023. All the pathology slides, including hematoxylin and eosin-stained sections, masson trichrome, jones methenamine silver, PAS, GMS, AFB, and immunohistochemistry (C4d, SV40) were reviewed. Pathologic findings were analyzed based on the transplant to nephrectomy interval (0-3 months, > 3 months) and type of donor (deceased, live donor). Of the total 103 cases, 77 were male. The mean age at the time of nephrectomy was 36.4 (range 5-64) years. The allografts were obtained from deceased (57) donors and live related (46) donors. Graft tenderness, oliguria/anuria, and fever were common clinical presentations. The majority (71.8%) of the nephrectomies were performed within the first 3 months of renal transplant. Renal vessel thrombosis (32.03%) was the most common pathologic finding. Infections were more common in the first 3 months after the transplant. Fungal infection had a significant association with deceased donor transplantation (p = 0.029). Histopathological study of allograft nephrectomy specimens aids understanding of graft loss causes. The study also provides opportunities to prevent complications and implement measures to prolong graft survival in a subsequent transplant.

International Travel for Organ Transplantation: Provider and Patient Perspectives.

Organ allocation in the United States to non-US citizen, non-US residents who travel for transplant (NC/NRTx) is controversial. Current policies may not be informed by stakeholder opinions, as limited data exist assessing the knowledge or opinions of providers or patients on this issue. A cross-sectional, hospital-based pilot survey was distributed to providers and patients from December 2019 to June 2020 at a single large urban transplant institute. Providers were members of the departments of surgery and medicine and included both transplant and nontransplant providers. Surveys included 10 questions on eligibility, prioritization, and limitations for deceased donor transplantation and 12 demographic questions. A total of 209 providers responded (61% women, median age 40) and 119 patients responded (62% women, median age 54). Awareness of eligibility for transplantation of US citizens, non-US citizens residing in the United States (NC/R), and NC/NRTx was high in both groups, though providers and patients lacked awareness of the eligibility of nonlegal NC/R (those who live in the United States who are not citizens and are not legal residents) to donate and receive organs. Overall, 79.3% of patients stated that NC/NRTx should be eligible for transplant in the United States compared with only 60.7% of providers (P = 0.001). Providers were more likely than patients to prioritize transplant to legal NC/NR over NC/NRTx (58.2% versus 35.1%, P < 000.1) and reported that families should be able to limit donations to NC/NRTx (34.9% versus 23.2%, P = 0.03). Surveyed patients and providers generally support transplant in non-US citizens; however, the strength of support varied considerably based on the legal status of the patient and the occupation of those surveyed. Larger studies are necessary to develop data-informed policy.

Serum from patients with cirrhosis undergoing liver transplantation induces permeability in human pulmonary microvascular endothelial cells ex vivo.

Patients with cirrhosis undergoing liver transplantation frequently exhibit systemic inflammation, coagulation derangements, and edema, indicating endothelial dysfunction. This syndrome may worsen after ischemia-reperfusion injury of the liver graft, coincident with organ dysfunction that worsens patient outcomes. Little is known about changes in endothelial permeability during liver transplantation. We hypothesized that sera from these patients would increase permeability in cultured human endothelial cells ex vivo. Adults with cirrhosis presenting for liver transplantation provided consent for blood collection during surgery. Sera were prepared at five time points spanning the entire operation. The barrier function of human pulmonary microvascular endothelial cells in culture was assessed by transendothelial resistance measured using the ECIS ZΘ system. Confluent cells from two different endothelial cell donors were stimulated with human serum from liver transplant patients. Pooled serum from healthy men and purified inflammatory agonists served as controls. The permeability response to serum was quantified as the area under the normalized resistance curve. Responses were compared between time points and analyzed for associations with clinical characteristics of liver transplant patients and their grafts. Liver transplant sera from all time points during surgery-induced permeability in both endothelial cell lines. The magnitude of permeability change was heterogeneous between patients, and there were differences in the effects of sera on the two endothelial cell lines. In one of the cell lines, the severity of liver disease was associated with greater permeability at the start of surgery. In the same cell line, serum collected 15 min after liver reperfusion induced significantly more permeability as compared to that collected at the start of surgery. Early postreperfusion sera from patients undergoing living donor transplants induced more permeability than sera from deceased donor transplants. Sera from two exemplary cases of patients on preoperative dialysis, and one patient with an unexpectedly long warm ischemia time of the liver graft, induced exaggerated and prolonged endothelial permeability. Serum from patients with cirrhosis undergoing liver transplantation induces permeability of cultured human pulmonary microvascular endothelial cells. Increased endothelial permeability during liver transplantation may contribute to organ injury and present a target for future therapeutics.

Factors Responsible for Nonselection of Donors in Living Related Kidney Transplantation.

Living donor kidney transplant is the preferred method of renal transplant in Pakistan as deceased donor transplant has not yet been estab-lished. However, many patients who are dialysis-dependent, particularly younger patients, lack suitable living related donors. We aimed to determine factors contributing to nonselection of donors for living related renal transplant in Pakistan. For this cross-sectional study, we included patients seen at the Sindh Institute of Urology & Transplantation Karachi, Pakistan) from March to November 2019. Potential donors were adult family members who accompanied patients with end-stage kidney disease to the clinic. Demographic and clinical information were recorded on predesigned proforma. After workup and baseline investigations had been completed, potential living related donors were selected. Factors leading to nonselection of donors were noted for those who did not qualify for donation. We used SPSS version 20 for analysis. During the study period, 253 potential donors (151 males, 102 females) with mean age of 35.68 ± 6.14 years were found to be ineligible for kidney donation. ABO incompatibility was the most common factor leading to nonselection (n = 101; 39.92%), followed by diabetes mellitus (n = 71; 28.06%), hypertension (n= 50; 19.76%), renal disease (n = 15; 5.92%), liver disease (n = 8; 3.16%), crossmatch positive (n = 5; 1.97%), and ischemic heart disease (n = 3; 1.18%). No differences were shown between potential male and female donors regarding factors leading to nonselection; diabetes was significantly more prevalent among those <40 years of age (P = .025). ABO incompatibility, diabetes mellitus, and hypertension were the most common factors leading to nonselection of potential donors in living related kidney transplant. More efforts are needed to expand the donor pool by considering second- or third-degree relatives to tackle the scarcity of organs for transplantation.

Erratum: Egyptian clinical practice guideline for deceased donor transplantation

Erratum: Egyptian clinical practice guideline for deceased donor transplantation

The survival benefit of deceased donor kidney transplantation for Aboriginal and Torres Strait Islander people, 2006-20: a retrospective national cohort study.

To quantify the survival benefit of kidney transplantation for Aboriginal and Torres Strait Islander people waitlisted for deceased donor kidney transplantation in Australia. Retrospective cohort study; analysis of linked data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry, the Australia and New Zealand Organ Donation (ANZOD) registry, and OrganMatch (Australian RedCross). All adult Aboriginal and Torres Strait Islander people (18 years or older) who commenced dialysis in Australia during 1 July 2006 - 31 December 2020 and were included in the kidney-only deceased donor transplant waiting list. Survival benefit of deceased donor kidney transplantation relative to remaining on dialysis. Of the 4082 Aboriginal and Torres Strait Islander people who commenced dialysis, 450 were waitlisted for kidney transplants (11%), of whom 323 received deceased donor transplants. Transplantation was associated with a significant survival benefit compared with remaining on dialysis after the first 12 months (adjusted hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.73). This benefit was similar to that for waitlisted non-Indigenous people who received deceased donor kidney transplants (adjusted HR, 0.47; 95% CI, 0.40-0.57; Indigenous status interaction: P=0.22). From twelve months post-transplantation, deceased donor transplantation provides a survival benefit for Aboriginal and Torres Strait Islander people. Our findings provide evidence that supports efforts to promote the waitlisting of Aboriginal and Torres Strait Islander people who are otherwise eligible for transplantation.

Challenges and opportunities for designing clinical trials for antibody mediated rejection.

Significant progress has been made in kidney transplantation, with 1-year graft survival nearing 95%. However, long-term allograft survival remains suboptimal, with a 10-year overall graft survival rate of only 53.6% for deceased donor transplant recipients. Chronic active antibody-mediated rejection (ABMR) is a leading cause of death-censored graft loss, yet no therapy has demonstrated efficacy in large, randomized trials, despite substantial investment from pharmaceutical companies. Several clinical trials aimed to treat chronic ABMR in the past decade have yielded disappointing results or were prematurely terminated, attributed to factors including incomplete understanding of disease mechanisms, heterogeneous patient populations with comorbidities, slow disease progression, and limited patient numbers. This review aims to discuss opportunities for improving retrospective and prospective studies of ABMR, focusing on addressing heterogeneity, outcome measurement, and strategies to enhance patient enrollment to inform study design, data collection, and reporting.