Impact of Centers for Medicare and Medicaid Services Final Rule on Organ Procurement Organization Metrics and Procedural Trends in the Procurement of Pancreata for Research.

OBJECTIVE: Pancreata recovered for research are included as a success (or positive) in the Centers for Medicare and Medicaid Services' (CMS) donation and organ transplantation rate metrics for recertification of organ procurement organizations (OPOs). MATERIALS AND METHODS: Given these metrics directly incentivize recovery of pancreata for research, this study tracks trends in recovery of pancreata for research across the implementation of the CMS metrics. RESULTS: In the 26 months before the December 2, 2020, publication of the CMS metrics, research pancreata as a percent of organs transplanted, including research pancreata, was 1.7% nationally, including as much as 10.8% of organs transplanted within any OPO. In the 26 months after the CMS metrics were published, research pancreata increased to 5.1% of organs counted as transplants nationally, including as much as 20.3% within any OPO. If research pancreata were excluded from the CMS metrics, 6 OPOs would change their CMS evaluation status for recertification purposes: 2 would move up a tier and 4 would move down a tier. CONCLUSIONS: Procurement of research pancreata has increased since the publication of the CMS performance metrics, OPOs vary in their recovery of pancreata for research, and recovery of pancreata for research can affect recertification of OPOs.

Sociodemographic Drivers of Donor and Recipient Gender Disparities in Living Kidney Donation in Australia.

Background: Females account for 60% of all living kidney donors worldwide. We defined the proportion of female to male donors for living donor kidney transplantation stratified by recipient gender, and explored the factors associated with female kidney donation. Methods: Data from the ANZDATA (Australian and New Zealand Dialysis and Transplantation) and ANZOD (Australian and New Zealand Organ Donor) registries (2002-2019) were used to identify the sociodemographic characteristics and their interactions associated with living donation from female donors. We derived the predicted probabilities from adjusted logistic models using marginal means. Results: Of 3523 living donor pairs, 2203 (63%) recipients were male, and 2012 (57%) donors were female. Male recipients were more likely to receive kidneys from female donors than male donors. Donor and recipient sex association was modified by donor-recipient relationship (P < 0.01), with sensitivity analysis suggesting that spousal donor-recipient pairs drive this interaction. Older recipients residing in regional or remote areas were more likely to receive kidneys from female donors compared with those from major cities (aged ≥60 years: 0.67 [0.63-0.71] vs. aged <60 years: 0.57 [0.53-0.60]). Conclusions: Factors associated with female donation include recipient sex, with spousal donors contributing to the interaction between recipient gender and donor-recipient relationship. Recipient age and location of residence have interactive effects on the likelihood of living donor transplantation from female donors.

Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report.

The Sensitization in Transplantation: Assessment of Risk workgroup is a collaborative effort of the American Society of Transplantation and the American Society of Histocompatibility and Immunogenetics that aims at providing recommendations for clinical testing, highlights gaps in current knowledge, and proposes areas for further research to enhance histocompatibility testing in support of solid organ transplantation. This report provides updates on topics discussed by the previous Sensitization in Transplantation: Assessment of Risk working groups and introduces 2 areas of exploration: non-human leukocyte antigen antibodies and utilization of human leukocyte antigen antibody testing measurement to evaluate the efficacy of antibody-removal therapies.

Impact of CYP3A5 Status on the Clinical and Financial Outcomes Among African American Kidney Transplant Recipients.

Pharmacogenetic profiling of transplant recipients demonstrates that the marked variation in the metabolism of immunosuppressive medications, particularly tacrolimus, is related to genetic variants. Patients of African ancestry are less likely to carry loss-of-function (LoF) variants in the CYP3A5 gene and therefore retain a rapid metabolism phenotype and higher clearance of tacrolimus. Patients with this rapid metabolism typically require higher dosing to achieve therapeutic trough concentrations. This study aims to further characterize the impact of CYP3A5 genotype on clinical outcomes and financial expenditure. Methods: The CYP3A5 phenotype status was identified in 438 adult kidney transplant (KTx) recipients (96% were African American) using 3 LoF alleles (CYP3A5*3, *6 or *7). Individuals were categorized as rapid metabolism phenotype without LoF alleles' intermediate phenotype for 1 LoF allele' and slow phenotype for 2 LoF alleles. KTx outcomes (patient/kidney survival and Medicare spending) were determined using linked transplant registry and claims data. Results: Among the cohort, 23% had a rapid, 47% intermediate, and 30% a slow metabolism phenotype based on genotype. At 3 y, the rate of death censored graft failure and all cause graft failure was highest in the rapid metabolism phenotype and lowest in the intermediate metabolism phenotype group. First-year Medicare reimbursement differed significantly by genotype (rapid: $79 535, intermediate: $72 796, slow: $79 346, P = 0.03). After adjustment for donor and recipient characteristics, care for patients with intermediate metabolism was $4790 less expensive (P = 0.003). Conclusions: Pharmacogenomic assessment of African American KTx recipients may be useful to guide therapy when as CYP3A5 functional variants appear to be associated with differential outcome and spending after transplant.

A multi-faceted approach to sex and gender equity in solid organ transplantation: The Women in Transplantation Initiative of The Transplantation Society.

The advancement of women's careers in transplantation continues to be challenging. Academic careers in both basic and clinical disciplines in transplantation, such as surgery and management of end organ failure in medical specialties, have been underrepresented by diverse genders and ethnicities. Over the last decade, the Women in Transplantation Initiative (WIT) has solidified to becoming an internationally recognized organization with activities focused on diversity and inclusion in terms of the sexes. The WIT organization is divided into 3 pillars that address career advancement and networking (Pillar 1), scientific investigation and presentations on sex and gender in transplantation (Pillar 2) and investigating and facilitating equitable access to transplantation for women throughout the world (Pillar 3). By taking this multipronged approach of collaborating across continents, leveraging virtual platforms for information dissemination and discussion, and providing financial support for research, WIT has become a highly visible grass roots organization that aims to improve the experience of women as transplant professionals as well as transplant donors and recipients.

Disparities in Deceased Organ Donor Research Authorization: Experience at One Organ Procurement Organization and Call for National Conversations.

INTRODUCTION: Research with deceased donor organs can provide an important platform for studying interventions to improve organ use and outcomes after authorization from the next-of-kin (NOK) or before death by the decedent (i.e., first-person authorization [FPA]). To date, information on authorization rates across donor subgroups is lacking. METHODS: We performed a retrospective chart review of all 690 deceased organ donors from January 2017 to December 2019 at a midsized Midwestern organ procurement organization (OPO). Multivariable logistic regression was used to assess associations between donor factors and research decline (adjusted odds ratio [aOR], 95% confidence interval [CI]). RESULTS: Electronic records for all 690 deceased donors were reviewed. Of these, 659 (95.5%) yielded at least one transplanted organ. Overall, research was declined in 10.8% of donations. Compared to White donors, research decline was higher for Black (16.0% vs. 8.9%; aOR, 1.87; 95% CI, 1.03-3.40; P = 0.04) and other non-White donors (24.0% vs. 8.9%; aOR, 4.21; 95% CI, 1.02-17.39; P = 0.05). Unadjusted research decline trended higher for Hispanic donors versus non-Hispanic donors (23.1% vs. 10.5%; P = 0.14). Compared to donors age <40 years, research decline trended higher for donors age ≥65 years (16.7% vs. 11.8%; aOR, 4.87; 95% CI, 1.12-21.05; P = 0.03), whereas research decline was 55% lower when donors provided FPA (7.3% vs 15.0%; aOR, 0.45; 95% CI, 0.27-0.76; P = 0.003). CONCLUSIONS: Deceased donor research authorization decline is higher for Black, other non-White, and older donors, but lower when the descendent provides FPA. Identification of disparities in research authorization may stimulate educational strategies to reduce barriers to scientific investigations directed at optimizing the outcomes of organ donation.

Sensitization in transplantation: Assessment of risk (STAR) 2019 Working Group Meeting Report.

The purpose of the STAR 2019 Working Group was to build on findings from the initial STAR report to further clarify the expectations, limitations, perceptions, and utility of alloimmune assays that are currently in use or in development for risk assessment in the setting of organ transplantation. The goal was to determine the precision and clinical feasibility/utility of such assays in evaluating both memory and primary alloimmune risks. The process included a critical review of biologically driven, state-of-the-art, clinical diagnostics literature by experts in the field and an open public forum in a face-to-face meeting to promote broader engagement of the American Society of Transplantation and American Society of Histocompatibility and Immunogenetics membership. This report summarizes the literature review and the workshop discussions. Specifically, it highlights (1) available assays to evaluate the attributes of HLA antibodies and their utility both as clinical diagnostics and as research tools to evaluate the effector mechanisms driving rejection; (2) potential assays to assess the presence of alloimmune T and B cell memory; and (3) progress in the development of HLA molecular mismatch computational scores as a potential prognostic biomarker for primary alloimmunity and its application in research trial design.

Meeting report of the STAR-Sensitization in Transplantation Assessment of Risk: Naïve Abdominal Transplant Organ subgroup focus on kidney transplantation.

The development of de novo donor-specific HLA antibody (dnDSA) is a critical feature contributing to late allograft failure. The complexity of the issue is further complicated by organ-specific differences, detection techniques, reliance of tissue histopathology and changing diagnostic criteria, ineffective therapies, and lack of consensus. To tackle these issues, the Sensitization in Transplantation Assessment of Risk (STAR) 2017 was initiated as a collaboration of the American Society of Transplantation and American Society of Histocompatibility and Immunogenetics consisting of 8 working groups with the goal to provide guidelines on how to assess risk and risk stratify patients based on their potential alloimmune and DSA status. Herein is a summary of discussions by the Naïve Abdominal Working Group, highlighting currently available data and identifying gaps in our knowledge on the development and impact of dnDSA following kidney transplantation.

Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report.

The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA vary markedly between centers. A collaborative effort between the American Society for Histocompatibility and Immunogenetics and the American Society of Transplantation provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as kidney, liver, heart, and lung transplantation. The goals were to perform a critical review of biologically driven, state-of-the-art, clinical diagnostics literature and to provide clinical practice recommendations based on expert assessment of quality and strength of evidence. The results of the Sensitization in Transplantation: Assessment of Risk (STAR) meeting are summarized here, providing recommendations on the definition and utilization of HLA diagnostic testing, and a framework for clinical assessment of risk for a memory or a primary alloimmune response. The definitions, recommendations, risk framework, and highlighted gaps in knowledge are intended to spur research that will inform the next STAR Working Group meeting in 2019.

Effect of a Mobile Web App on Kidney Transplant Candidates' Knowledge About Increased Risk Donor Kidneys: A Randomized Controlled Trial.

BACKGROUND: Kidney transplant candidates (KTCs) must provide informed consent to accept kidneys from increased risk donors (IRD), but poorly understand them. We conducted a multisite, randomized controlled trial to evaluate the efficacy of a mobile Web application, Inform Me, for increasing knowledge about IRDs. METHODS: Kidney transplant candidates undergoing transplant evaluation at 2 transplant centers were randomized to use Inform Me after routine transplant education (intervention) or routine transplant education alone (control). Computer adaptive learning method reinforced learning by embedding educational material, and initial (test 1) and additional test questions (test 2) into each chapter. Knowledge (primary outcome) was assessed in person after education (tests 1 and 2), and 1 week later by telephone (test 3). Controls did not receive test 2. Willingness to accept an IRD kidney (secondary outcome) was assessed after tests 1 and 3. Linear regression test 1 knowledge scores were used to test the significance of Inform Me exposure after controlling for covariates. Multiple imputation was used for intention-to-treat analysis. RESULTS: Two hundred eighty-eight KTCs participated. Intervention participants had higher test 1 knowledge scores (mean difference, 6.61; 95% confidence interval [95% CI], 5.37-7.86) than control participants, representing a 44% higher score than control participants' scores. Intervention participants' knowledge scores increased with educational reinforcement (test 2) compared with control arm test 1 scores (mean difference, 9.50; 95% CI, 8.27-10.73). After 1 week, intervention participants' knowledge remained greater than controls' knowledge (mean difference, 3.63; 95% CI, 2.49-4.78) (test 3). Willingness to accept an IRD kidney did not differ between study arms at tests 1 and 3. CONCLUSIONS: Inform Me use was associated with greater KTC knowledge about IRD kidneys above routine transplant education alone.

The Cost of Transplant Immunosuppressant Therapy: Is This Sustainable?

A solid organ transplant is life-saving therapy that engenders the use of immunosuppressive medications for the lifetime of the transplanted organ and its recipient. Conventional therapy includes both induction therapy (a biologic that is infused peri-operatively) followed by maintenance therapy. The cost of these medications is a constant concern and the advent of generics has brought this cost down modestly. For those lacking long term insurance coverage, this may be a significant out of pocket expense that is not affordable. Moreover, transplant Centers are managing higher risk transplant recipients that require more complex induction regimens and longer term use of such biologic agents in the context of desensitization or abrogation of de novo antibody mediated injury. While in kidney transplantation, Medicare part B covers three years of medication, there is frequent non-adherence due to cost after that time-point. The impact of the Affordable Care Act remains uncertain at this time. Finally the pipeline of new therapies is limited due to the cost of development of a drug, the inherent cost of clinical studies, and lack of defined endpoints for newer therapies in high risk patients. These new therapies are of high value to the community but will contribute additional burden to current drug costs.

Identification of strategies to facilitate organ donation among African Americans using the nominal group technique.

BACKGROUND AND OBJECTIVES: African Americans are disproportionately affected by ESRD, but few receive a living donor kidney transplant. Surveys assessing attitudes toward donation have shown that African Americans are less likely to express a willingness to donate their own organs. Studies aimed at understanding factors that may facilitate the willingness of African Americans to become organ donors are needed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A novel formative research method was used (the nominal group technique) to identify and prioritize strategies for facilitating increases in organ donation among church-attending African Americans. Four nominal group technique panel interviews were convened (three community and one clergy). Each community panel represented a distinct local church; the clergy panel represented five distinct faith-based denominations. Before nominal group technique interviews, participants completed a questionnaire that assessed willingness to become a donor; 28 African-American adults (≥19 years old) participated in the study. RESULTS: In total, 66.7% of participants identified knowledge- or education-related strategies as most important strategies in facilitating willingness to become an organ donor, a view that was even more pronounced among clergy. Three of four nominal group technique panels rated a knowledge-based strategy as the most important and included strategies, such as information on donor involvement and donation-related risks; 29.6% of participants indicated that they disagreed with deceased donation, and 37% of participants disagreed with living donation. Community participants' reservations about becoming an organ donor were similar for living (38.1%) and deceased (33.4%) donation; in contrast, clergy participants were more likely to express reservations about living donation (33.3% versus 16.7%). CONCLUSIONS: These data indicate a greater opposition to living donation compared with donation after one's death among African Americans and suggest that improving knowledge about organ donation, particularly with regard to donor involvement and donation-related risks, may facilitate increases in organ donation. Existing educational campaigns may fall short of meeting information needs of African Americans.

Solid organ transplantation at the National Institutes of Health: development of a research-based transplantation practice.

The National Institutes of Health has established a clinical transplant research program focusing on translational research in kidney transplantation. The program has been developed with a multidisciplinary approach under a common administrative structure that integrates transplant physicians and surgeons with clinical laboratory and data analysis support personnel. The program has achieved excellent clinical outcomes despite focusing exclusively on investigational methods and serving a diverse and medically complex patient population. Novel approaches toward consenting, computer integration, and tissue acquisition have been layered over interventional and observational studies to serve the scientific mission while delivering quality transplant care.