Access To Transplantation Research Articles

Sex/Gender-Based Disparities in Early Transplant Access by Attributed Cause of Kidney Disease–Evidence from a Multiregional Cohort in the Southeast United States

We examined sex/gender disparities across the continuum of transplant care by attributed cause of end-stage kidney disease (ESKD). All adults (18-79 years; N= 43,548) with new-onset ESKD in Georgia, North Carolina, or South Carolina between 2015 and 2019 were identified from the United States Renal Data System (USRDS). Individuals were linked to the Early Steps to Transplant Access Registry (E-STAR) to obtain data on referral and evaluation. Waitlisting data was ascertained from USRDS. Using a Cox-proportional hazards model, with follow-up through 2020, we assessed the association between sex/gender and referral within 12 months (among all incident dialysis patients), evaluation start within 6 months (among referred patients), and waitlisting (among all evaluated patients) by attributed cause of ESKD (type 1 diabetes mellitus, type 2 diabetes mellitus, hypertension, glomerulonephritis, cystic disease, and other). Overall, women (vs. men) with type 2 diabetes-attributed ESKD were 13% (crude hazard ratio [HR]: 0.87 [0.83-0.91]), 14% (crude HR: 0.86 [0.81-0.91]), and 14% (crude HR: 0.86 [0.78-0.94]) less likely to be referred, evaluated, and waitlisted, respectively. Women (vs. men) with hypertension-attributed ESKD were 14% (crude HR: 0.86 [0.82-0.90]) and 8% (crude HR: 0.92 [0.87-0.98]) less likely to be referred and evaluated, respectively, but similarly likely to be waitlisted once evaluated (crude HR: 1.06 [0.97-1.15]). For all other attributed causes of ESKD, there was no sex/gender disparity in referral, evaluation, or waitlisting rates. In the Southeast United States, sex/gender disparities in early access to kidney transplantation are specific to people with ESKD attributed to type 2 diabetes and hypertension.

SP5.6 A UK-wide audit on peri-operative practices during deceased donor kidney transplantation: Results from a prospective National Transplant ACcess to Theatre (NTACT) Audit

Abstract Background The outcomes of deceased donor kidney transplants are mainly affected by donor and recipient factors. There is little data on standard perioperative practices across the UK and whether variations in perioperative practices could affect the outcomes. This national audit aims to identify current perioperative practices. Methods We conducted a multicentre, prospective audit of adult deceased donor kidney-only transplants across 14 UK transplant centres between February and September 2022. Data was collected on pre-operative antibiotic use, clinician’s grade, fluid management, central/arterial line insertion, post-operative destination, crossmatch and advanced haemodynamic monitoring use. Data was recorded on RedCap and analysed using descriptive statistics. Results 476 kidney-only transplants were recorded (59 were excluded for incomplete/incorrect data), leaving 417 transplants. In 98.6% of transplants, patients received antibiotics pre-operatively. A wide range of antibiotics were given; the three most used were co-amoxiclav (n=135), ciprofloxacin (n=92) and amikacin (n=62). Most operations were led by a consultant surgeon (91.1% n=380). However, only 60.1% of cases were led by consultant anaesthetists. Central lines were used in 65.5% (273/417) of patients, 41.0% (171/417) used an arterial line, and 25.4% (106/417) had advanced haemodynamic monitoring. A total of 289 cases (69.3%) received goal-directed fluid therapy, of which 74.4% (215/289) used static parameters. Most common post-operative destinations were the transplant ward, 75.3% (n=314), ICU, 9.4% (n=39) and HDU, 10.1% (n=42). Conclusions We identified wide variations in certain perioperative practices. In the future, we would like to assess whether there is any relationship between the variations in practice and postoperative outcomes, such as graft function and mortality.

WTP2.9 Early Deceased Donor Kidney Transplant outcomes: Results from a Prospective National Transplant Access to Theatre (NTACT) Audit

Abstract Background Renal transplantation is increasing, yet there is a paucity of data describing post-operative complications. Therefore, this national audit aims to identify the incidence of early complications that impact patient outcomes. Methods We conducted a multicentre, prospective audit of adult deceased donor kidney-only transplants across 14 UK transplant centres between February and September 2022. Data was collected on significant checkpoints pre, intra and post-operatively, assessing for 30-day complication and mortality rates. Data was recorded on RedCap and analysed using descriptive statistics. Results 476 kidney-only transplants were recorded, (59 excluded for incomplete/incorrect data). Of 417, 215 were donation after brainstem death (DBD) organs and 202 were donation after circulatory death (DCD) organs. The 30-day mortality was 0.47% (n=2/417). The primary graft function rate was 81%. The 30-day readmission rate was 18%, and median number of readmissions was 1 (IQR: 1-3). Of the readmitted recipients, 92% were readmitted once and 8% were readmitted more than. The 30-day reoperation rate was 12%, and median number of reoperations was 1 (IQR: 1-2), of these, 91% had 1 reoperation and 9% had more than 1 reoperation. Most common indications for reoperations were bleeding 49% (n=25), assessment of graft perfusion 17% (n=9), and wound dehiscence 10% (n=5). We noted a difference in rates of reoperations between DCD and DBD organs, 16% and 9% respectively, however, this was not significant. There was no significant difference in the readmission and mortality rate between DBD and DCD organs. Conclusion The overall early postoperative complication rates and 30-day mortality following deceased donor kidney transplantation are low.

SP3.4 Barriers to deceased donor kidney organ utilisation: Results of a National Transplant ACcess to Theatre (NTACT) Audit

Abstract Aims Various barriers to deceased-donor kidney utilisation exist, however, there is a lack of data on these; therefore, this national audit aims to identify the barriers to prompt kidney utilisation after the arrival of organs at the implanting centre (IC). Methods We conducted a multicentre, prospective audit of adult deceased-donor kidney-only transplants across 14 UK centres between February and September 2022. Data was collected on time-intervals between significant checkpoints before transplantation and perceived reasons for delays. Data was recorded on RedCap and analysed using descriptive statistics. Results 476 kidney-only transplants were recorded (59 excluded-incomplete/incorrect data). There were 215 donations after brainstem death (DBD) organs and 202 donation after circulatory death (DCD) organs. The median cold ischaemia time (CIT) for DBD organs was 10:51 (IQR: 08:07-14:44), and for DCD organs was 11:09 (IQR: 08:13-14:50). The national CIT recommendations were exceeded by 40% of DCD and 14% of DBD organs. The median time-interval between the organ’s arrival at IC and knife-to-skin was 04:16 (IQR 02:46-07:52). The median time-interval between anaesthetic induction and knife-to-skin was 00:55 (IQR: 00:39-01:10). In 17% of cases, crossmatch results arrived after organ arrival at IC, median delay was 02:30 (IQR: 00:56-04:27). Delays were reported in 34% of cases, availability of the surgical team, anaesthetic team, porters, and the operating theatre were the most common causes of delay. Conclusions A significant proportion of kidneys were implanted beyond nationally recommended CIT. This audit delineated the current timings of each stage of the transplantation process and will be used in future to set realistic targets to optimise current practice.

Living donor liver transplantation can address disparities in transplant access for patients with primary sclerosing cholangitis.

Liver transplantation (LT) is frequently lifesaving for people living with primary sclerosing cholangitis (PSC). However, patients are waitlisted for LT according to the model for end-stage liver disease-sodium (MELD-Na) score, which may not accurately reflect the burden of living with PSC. We sought to describe and analyze the clinical trajectory for patients with PSC referred for LT, in a mixed deceased donor/living donor transplant program. This was a retrospective cohort study from November 2012 to December 2019, including all patients with PSC referred for assessment at the University Health Network Liver Transplant Clinic. Patients who required multiorgan transplant or retransplantation were excluded. Liver symptoms, hepatobiliary malignancy, MELD-Na progression, and death were abstracted from chart review. Competing risk analysis was used for timing of LT, transplant type, and death. Of 172 PSC patients assessed, 84% (n = 144) were listed of whom 74% were transplanted. Mean age was 47.6 years, and 66% were male. Overall mortality was 18.2% at 2 years. During the follow-up, 16% (n = 23) were removed from the waitlist for infection, clinical deterioration, liver-related mortality or new cancer; 3 had clinical improvement. At listing, 82% (n = 118) had a potential living donor (pLD). Patients with pLD had significantly lower waitlist and liver-related waitlist mortality (HR 0.20, p<0.001 and HR 0.17, p<0.001, respectively), and higher rates of transplantation (HR 1.83, p = 0.05). Exception points were granted to 13/172 (7.5%) patients. In a high-volume North American LT center, most patients with PSC assessed for transplant were listed and subsequently transplanted. However, this was a consequence of patients engaging in living donor transplantation. Our findings support the concern from patients with PSC that MELD-Na allocation does not adequately address their needs.

Pre-dialysis care trajectory and post-dialysis survival and transplantation access in patients with end-stage kidney disease.

The pre-dialysis care trajectory impact on post-dialysis outcomes is poorly known. This study assessed survival, access to kidney transplant waiting list and to transplantation after dialysis initiation by taking into account the patients' pre-dialysis care consumption (inpatient and outpatient) and the conditions of dialysis start: initiation context (emergency or planned) and vascular access type (catheter or fistula). Adults who started dialysis in France in 2015 were included. Clinical data came from the French REIN registry and data on the care trajectory from the French National Health Data system (SNDS). The Cox model was used to assess survival and access to kidney transplantation. We included 8856 patients with a mean age of 68years. Survival was shorter in patients with emergency or planned dialysis initiation with a catheter compared to patients with planned dialysis with a fistula. The risk of death was lower in patients who were seen by a nephrologist more than once in the 6months before dialysis than in those who were seen only once. The rate of kidney transplant at 1year post-dialysis was lower for patients with emergency or planned dialysis initiation with a catheter (respectively, HR = 0.5 [0.4; 0.8] and HR = 0.7 [0.5; 0.9]) compared to patients with planned dialysis start with a fistula. Patients who were seen by a nephrologist more than three times between 0 and 6months before dialysis start were more likely to access the waiting list 1 and 3years after dialysis start (respectively, HR = 1.3 [1.1; 1.5] and HR = 1.2 [1.1; 1.4]). Nephrological follow-up in the year before dialysis initiation is associated with better survival and higher probability of access to kidney transplantation. These results emphasize the importance of early patient referral to nephrologists by general practitioners.

Access to treatment in chronic kidney disease, dialysis and transplantation. Is there gender equality?

Sex and gender are often used as synonyms. However, while sex describes only a biological state, gender is a dynamic concept that takes into account psychosocial and cultural aspects of human existence that can change according to place and time. Inequality in medicine has been described in several areas. Among them, gender inequality has been disregarded for many years and is now a matter of concern. Chronic kidney disease (CKD) is a growing epidemic worldwide, affecting approximately 10% of the population. Although both men and women are affected, gender equality, especially in access to different treatments, is a matter of concern. We decided to investigate gender equality in patients with CKD. To this end, we conducted a literature narrative review to determine whether gender inequalities were found in CKD patients in general and in access to different treatment modalities in particular. A non-language restricted search was performed until November 30th 2022 in PubMed, SciELO, Trip Database, Google Scholar, MEDES y MEDLINE. We also investigated the situation in this regard in our country. We found that CKD is more prevalent in women than men, nevertheless this prevalence decreases along the CKD stages to the point that more men reach end stage kidney disease (ESKD) and dialysis. Access to transplant (ATT) is higher in men than in women although posttransplant survival shows no gender differences. Finally, most series have shown that women are more frequently Kidney transplantation (KT) living donors than men. Results in our country are similar to the published literature with the exception of a higher proportion of men as KT living donors. As in other areas, gender inequality in Nephrology has been largely overlooked. In this review we have highlighted gender differences in CKD patients. Gender inequality in Nephrology exists and needs to be looked upon in order to reach a personalized clinical approach.

#6257 PROGNOSTIC VALUE OF A POSITIVE CROSSMATCH BEFORE DESENSITIZATION IN A COHORT OF HIGHLY-SENSITIZED PATIENTS

Abstract Background and Aims Human Leukocyte antigen (HLA) sensitization in patients is a barrier for Kidney Transplantation (KT) access, and highly-sensitized patients remain on the waiting list longer than other patients which results in a higher morbidity and mortality. Desensitization may be an option to increase their access to KT. All patients transplanted in this context have a negative Complement-Dependent Cytotoxicity crossmatch (CDC-CM) the day of KT. However, the stratification of the long-term risk of graft loss according to flow cytometry crossmatch (FC-CM) and to CDC-CM during the desensitization period remains unknown. Method In this retrospective study, all highly-sensitized patients (Panel Reactive Antigen (PRA) ≥ 85) in our center were included. CDC-CM and FC-CM were performed on samples before and during the desensitization period and clinical follow-up data were retrieved. Pre-KT desensitization strategy consisted in two Rituximab infusions (375mg/m2) and a variable number of apheresis (mostly semi-specific immunoadsorption) associated with a classical immunosuppression-based regimen (tacrolimus, mycophenolate and steroids). Results A total of 183 highly-sensitized recipients received a KT between 2014 and 2022. Of these, 23 were desensitized prior to KT and among them 18 had a positive FC-CM before KT and 5 had no positive FC-CM on all assessed serums. Mean age was 52.9 ± 13 years. Mean follow-up was 5.2±4 and 3±2 years for non-desensitized and desensitized patients respectively. PRA before desensitization was higher in desensitized patients (98%) versus non-desensitized patients (95%) and the mean time on the waiting list was 5.8±4 versus 7.5±4 years respectively. Death-censored graft survival and patient's raw survival, using cox-survival analysis, were not statistically different between the desensitized kidney transplanted patients and the highly-sensitized patients without desensitization (p = 0.77 and p = 0.57 respectively). In sub-group analyses, the positivity of FC and/or CDC-CM did not add an additional risk of graft loss or patient mortality. Conclusion Desensitization allows highly-sensitized patients to access KT with an HLA-incompatible graft (with a positive CDC or FC-CM on the serum collected prior to desensitization), with the same graft survival as similarly sensitized patients transplanted with an HLA-compatible graft without desensitization.

Is the Affordable Care Act Moving the Needle for Advanced Heart Failure Therapies for Black Patients?

Is the Affordable Care Act Moving the Needle for Advanced Heart Failure Therapies for Black Patients?

Identifying and understanding variation in population-based access to liver transplantation in the United States

We aimed to identify variations in liver transplant access across transplant referral regions (TRRs), accounting for differences in population characteristics and practice environments. Adult end-stage liver disease (ESLD) deaths and liver waitlist additions from 2015 to 2019 were included. The primary outcome was listing-to-death ratio (LDR). We modeled the LDR as a continuous variable and obtained adjusted LDR estimates for each TRR, accounting for clinical and demographic characteristics of ESLD decedents, socioeconomic and health care environment within the TRR, and characteristics of the transplant environment. The overall mean LDR was 0.24 (range: 0.10-0.53). In the final model, proportion of patients living in poverty and concentrated poverty was negatively associated with LDR; organ donation rate was positively associated with LDR. The R2 was 0.60, indicating that 60% of the variability in LDR was explained by the model. Approximately 40% of this variation remained unexplained and may be due to transplant center behaviors amenable to intervention to improve access to care for patients with ESLD.

Pancreatic Islet Transplantation in Patients suffering from Type 1 diabetes - Indications, methods, possible risks and future directions: A literature review

&#x0D; Introduction: Type 1 diabetes is a common and debilitating disease that requires regular glycemic control to prevent potentially fatal hypoglycemia.&#x0D; &#x0D; &#x0D; Objective: The aim of this study is to demonstrate the purpose, process, and consequences of pancreatic islet transplantation in patients with type 1 diabetes. Additionally, the results of the procedure after several years are described based on the available publications.&#x0D; &#x0D; &#x0D; Materials and Methods: The authors created a summary of available publications on pancreatic islet transplantation, based on databases such as PubMed and Google Scholar. Using the terms listed in the "key words" section, the authors searched for relevant information in other scientific papers to create the following review. &#x0D; &#x0D; &#x0D; Conclusions: Reducing the number of donors and developing alternative sources of pancreatic islet cells for transplantation is an active area of research, that promises to expand access and indications for pancreatic islet transplantation in future diabetes treatment.&#x0D;

Increased volume of organ offers and decreased efficiency of kidney placement under circle-based kidney allocation

The newest kidney allocation policy kidney allocation system 250 (KAS250) broadened geographic distribution while increasing allocation system complexity. We studied the volume of kidney offers received by transplant centers and the efficiency of kidney placement since KAS250. We identified deceased-donor kidney offers (N = 907,848; N = 36,226 donors) to 185 US transplant centers from January 1, 2019, to December 31, 2021 (policy implemented March 15, 2021). Each unique donor offered to a center was considered a single offer. We compared the monthly volume of offers received by centers and the number of centers offered before the first acceptance using an interrupted time series approach (pre-/post-KAS250). Post-KAS250, transplant centers received more kidney offers (level change: 32.5 offers/center/mo, P < .001; slope change: 3.9 offers/center/mo, P = .003). The median monthly offer volume post-/pre-KAS250 was 195 (interquartile range 137-253) vs. 115 (76-151). There was no significant increase in deceased-donor transplant volume at the center level after KAS250, and center-specific changes in offer volume did not correlate with changes in transplant volume (r = −0.001). Post-KAS250, the number of centers to whom a kidney was offered before acceptance increased significantly (level change: 1.7 centers/donor, P < .001; slope change: 0.1 centers/donor/mo, P = .014). These findings demonstrate the logistical burden of broader organ sharing, and future allocation policy changes will need to balance equity in transplant access with the operational efficiency of the allocation system.

Impact of newly diagnosed prostate cancer at time of evaluation for renal transplantation.

Systematic screening for prostate cancer is widely recommended in candidates for renal transplant at the time of listing. There are concerns that overdiagnosis of low-risk prostate cancer may result in reducing access to transplant without demonstrated oncological benefits. The objective of the study was to assess the outcome of newly diagnosed prostate cancer in candidates for transplant at the time of listing, and its impact on transplant access and transplant outcomes according to treatment options. This retrospective study was conducted over 10 years in 12 French transplant centers. Patients included were candidates for renal transplant at the time of prostate cancer diagnosis. Demographical and clinical data regarding renal disease, prostate cancer, and transplant surgery were collected. The primary outcome of the study was the interval between prostate cancer diagnosis and active listing according to treatment options. Overall median time from prostate cancer diagnosis to active listing was 25.0 months [16.4-40.2], with statistically significant differences in median time between the radiotherapy and the active surveillance groups (p=.03). Prostate cancer treatment modalities had limited impact on access and outcome of renal transplantation. Active surveillance in low-risk patients does not seem to compromise access to renal transplantation, nor does it impact oncological outcomes.

The Transplantation Ecosystem: A New Concept to Improve Access and Outcomes for Older Allogeneic Hematopoietic Cell Transplantation Patients

Allogeneic hematopoietic cell transplantation (HCT) is increasingly offered to older adults with hematologic malignancies, even though nonrelapse mortality remains a major concern in older patients owing to more comorbidities and greater frailty compared with their younger counterparts. The importance of patient fitness, a well-matched donor, and disease control to the success of allogeneic HCT have been well documented; however, these factors fail to account for the impact of the complex transplantation ecosystem (TE) that older adult HCT candidates must navigate. We propose a definition of the TE modeled after the social determinants of health. Furthermore, we outline a research agenda aimed at increasing understanding of the roles of individual social determinants of transplantation health in the larger ecosystem and how they may benefit or harm older adult HCT candidates. Herein we define the TE and its individual tenets, the social determinants of transplantation health. We review the available literature while incorporating the expertise of the membership of the American Society for Transplantation and Cellular Therapy (ASTCT) Special Interest Group for Aging. The membership of the ASTCT Special Interest Group for Aging identify knowledge gaps and strategies to address them for each of the described social determinants of transplantation health. The ecosystem is an essential but underappreciated pillar for transplant access and success. We put forth this novel research agenda seeking to gain a better understanding of the complexity of HCT in older adults and develop strategies to improve access to HCT, survival, and quality of life.

Liver transplantation for alcohol-associated liver disease: A call for national standards of best practices to monitor and bridge disparities in access and outcomes

Early (ie, without a mandated abstinence period) liver transplantation for alcohol-associated liver disease is the fastest-growing indication for liver transplantation in the United States. Despite widespread adoption, there is no standardization of practice or policies across transplant centers, nor are there any quality metrics from regulatory organizations specific to alcohol, all of which have likely contributed to confirmed disparities in transplant access and patient outcomes. In this article, we propose new mandates and best practices that could be put forth by the organ procurement and transplantation network regarding processes related to candidate selection, monitoring of alcohol use, and services to prevent and treat harmful alcohol use among early transplant candidates and recipients. We hope that this article stimulates discussion and leads to policy changes to maximize equity and quality of transplant care.

Evaluating the Potential for ABO-incompatible Islet Transplantation: Expression of ABH Antigens on Human Pancreata, Isolated Islets, and Embryonic Stem Cell-derived Islets.

ABO-incompatible transplantation has improved accessibility of kidney, heart, and liver transplantation. Pancreatic islet transplantation continues to be ABO-matched, yet ABH antigen expression within isolated human islets or novel human embryonic stem cell (hESC)-derived islets remain uncharacterized. We evaluated ABH glycans within human pancreata, isolated islets, hESC-derived pancreatic progenitors, and the ensuing in vivo mature islets following kidney subcapsular transplantation in rats. Analyses include fluorescence immunohistochemistry and single-cell analysis using flow cytometry. Within the pancreas, endocrine and ductal cells do not express ABH antigens. Conversely, pancreatic acinar tissues strongly express these antigens. Acinar tissues are present in a substantial portion of cells within islet preparations obtained for clinical transplantation. The hESC-derived pancreatic progenitors and their ensuing in vivo-matured islet-like clusters do not express ABH antigens. Clinical pancreatic islet transplantation should remain ABO-matched because of contaminant acinar tissue within islet preparations that express ABH glycans. Alternatively, hESC-derived pancreatic progenitors and the resulting in vivo-matured hESC-derived islets do not express ABH antigens. These findings introduce the potential for ABO-incompatible cell replacement treatment and offer evidence to support scalability of hESC-derived cell therapies in type 1 diabetes.

Contextual Vulnerability Should Guide Fair Subject Selection in Xenotransplantation Clinical Trials

Contextual Vulnerability Should Guide Fair Subject Selection in Xenotransplantation Clinical Trials

Changes in socioeconomic status and patient outcomes in kidney transplantation recipients in South Korea.

Socioeconomic status is an important factor affecting the accessibility and prognosis of kidney transplantation. We aimed to investigate changes in kidney transplant recipients' socioeconomic status in South Korea and whether such changes were associated with patient prognosis. This retrospective nationwide observational cohort study in South Korea included kidney transplant recipients between 2007 and 2016. South Korea provides a single-insurer health insurance service, and information on the socioeconomic status of the recipients is identifiable through the claims database. First, a generalized linear mixed model was used to investigate changes in recipients' socioeconomic status as an outcome. Second, the risk of graft failure was analyzed using Cox regression as another outcome to investigate whether changes in socioeconomic status were associated with patient prognosis. Among the 15,215 kidney transplant recipients included in the study, economic levels (defined based on insurance fee percentiles) and employment rates declined within the first 2 years after transplantation. Beyond 2 years, the employment rate increased significantly, while no significant changes were observed in economic status. Patients whose economic status did not improve 3 years after kidney transplantation showed a higher risk of death than those whose status improved. When compared to those who remained employed after kidney transplantation, unemployment was associated with a significantly higher risk of death-censored graft failure. The socioeconomic status of kidney transplant recipients changed dynamically after kidney transplantation, and these changes were associated with patient prognosis.

Current and emerging therapeutic strategies in adult T-cell leukemia-lymphoma.

Adult T-cell leukemia-lymphoma (ATL) is classified into four clinical subtypes: acute, lymphoma, chronic, and smoldering. Chronic ATL is further divided into unfavorable and favorable chronic types according to serum lactate dehydrogenase, blood urea nitrogen, and serum albumin values. Acute, lymphoma, and unfavorable chronic types are categorized as aggressive ATL, whereas favorable chronic and smoldering types are categorized as indolent ATL. Intensive chemotherapy alone is not sufficient to prevent relapse of aggressive ATL. Allogeneic hematopoietic stem cell transplantation is a potential therapeutic option to cure aggressive ATL in younger patients. Reduced-intensity conditioning regimens have decreased transplantation-related mortality, and increased donor availability has dramatically improved transplant access. New agents, including mogamulizumab, brentuximab vedotin, tucidinostat, and valemetostat, have recently become available for patients with aggressive ATL in Japan. Here, I provide an overview of recent advances in therapeutic strategies for ATL.

Living donor liver transplant: A strategy to increase transplant access

Living donor liver transplant: A strategy to increase transplant access