Individual-level social determinants of health and disparities in access to kidney transplant and waitlist mortality.

BACKGROUND: Comprehensive, individual-level social determinants of health (SDOH) are not collected in national transplant registries, limiting research aimed at understanding the relationship between SDOH and waitlist outcomes among kidney transplant candidates. METHODS: We merged Organ Procurement and Transplantation Network data with individual-level SDOH data from LexisNexis, a commercial data vendor, and conducted a competing risk analysis to determine the association between individual-level SDOH and the cumulative incidence of living donor kidney transplant (LDKT), deceased donor kidney transplant (DDKT), and waitlist mortality. We included adult kidney transplant candidates placed on the waiting list in 2020, followed through December 2023. RESULTS: In multivariable analysis, having public insurance (Medicare or Medicaid), less than a college degree, and any type of derogatory record (liens, history of eviction, bankruptcy and/ felonies) were associated with lower likelihood of LDKT. Compared with patients with estimated individual annual incomes ≤ $30,000, patients with incomes ≥ $120,000 were more likely to receive a LDKT (sub distribution hazard ratio (sHR), 2.52; 95% confidence interval (CI), 2.03-3.12). Being on Medicare (sHR, 1.49; 95% CI, 1.42-1.57), having some college or technical school, or at most a high school diploma were associated with a higher likelihood of DDKT. Compared with patients with incomes ≤ $30,000, patients with incomes ≥ $120,000 were less likely to receive a DDKT (sHR, 0.60; 95% CI, 0.51-0.71). Lower individual annual income, having public insurance, at most a high school diploma, and a record of liens or eviction were associated with higher waitlist mortality. CONCLUSIONS: Patients with adverse individual-level SDOH were less likely to receive LDKT, more likely to receive DDKT, and had higher risk of waitlist mortality. Differential relationships between SDOH, access to LDKT, DDKT, and waitlist mortality suggest the need for targeted interventions aimed at decreasing waitlist mortality and increasing access to LDKT among patients with adverse SDOH.

Contemporary Prevalence and Practice Patterns of Out-of-Sequence Kidney Allocation.

Since 2021, the OPTN has reported a nearly 10-fold rise in out-of-sequence (OOS) kidney allocation, generating concern and halting development of continuous distribution policies. We report contemporary (2022-2023) practice patterns in OOS allocation using OPTN data. We examined in sequence vs. OOS donors with multivariable logistic regression and skipped vs. OOS-accepting recipients with conditional logistic regression. Nearly 20% of kidney placements were OOS, varying from 0% to 43% across OPOs; the 5 highest-OOS OPOs accounted for 29% of all OOS. Of OOS kidneys, 33% were declined >100 times in the standard allocation sequence and 51% were declined by >10 centers before OOS allocation began; 4.5% were made without any in-sequence declines. Nearly all OOS offers were open offers. OOS kidneys were more likely to be from female, Black, older, DCD, hypertensive, diabetic, and elevated creatinine donors. Candidates receiving OOS kidneys were more likely female, Asian, and older than skipped candidates. Higher-volume centers and centers with more White, fewer Hispanic, and more educated waiting list patients transplanted disproportionately more OOS kidneys. These findings suggest that the current, highly variable, discretionary use of OOS might exacerbate disparities, yet the impact of OOS on organ utilization cannot be determined with data now collected.

National Attitudes Toward Living Kidney Donation in the United States: Results of a Public Opinion Survey.

Rationale & Objective: Understanding national attitudes about living kidney donation will enable us to identify and address existing disincentives to living kidney donation. We performed a national survey to describe living kidney donation perceptions, perceived factors that affect the willingness to donate, and analyzed differences by demographic subgroups. Study Design: The survey items captured living kidney donation awareness, living kidney donation knowledge, willingness to donate, and barriers and facilitators to living kidney donation. Setting & Population: We surveyed 802 US adults (aged 25-65 years) in June 2021, randomly selected from an online platform with diverse representation. Analytical Approach: We developed summed, scaled indices to assess the association between the living kidney donation knowledge (9 items) and the willingness to donate (8 items) to self-reported demographic characteristics and other variables of interest using analysis of variance. All other associations for categorical questions were calculated using Pearson's χ2 and Fisher exact tests. We inductively evaluated free-text responses to identify additional barriers and facilitators to living kidney donation. Results: Most (86.6%) of the respondents reported that they might or would definitely consider donating a kidney while they were still living. Barriers to living kidney donation included concerns about the risk of the surgery, paying for medical expenses, and potential health effects. Facilitators to living kidney donation included having information on the donation surgery's safety, knowing that the donor would not have to pay for medical expenses related to the donation, and hearing living kidney donation success stories. Awareness of the ability to participate in kidney-paired donation was associated with a higher willingness to donate. Limitations: Potential for selection bias resulting from the use of survey panels and varied incentive amounts, and measurement error related to respondents' attention level. Conclusions: Most people would consider becoming a living kidney donor. Increased rates of living kidney donation may be possible with investment in culturally competent educational interventions that address risks associated with donating, policies that reduce financial disincentives, and communication campaigns that raise awareness of kidney-paired donation and living kidney donation.

Understanding what the general public thinks about living kidney donation will help to develop better education and increase the number of living kidney donors. We surveyed the public to find out: (1) how aware they are about the opportunity to donate a kidney while alive; (2) how much they know about living kidney donation; (3) whether they would be willing to donate; and (4) what would affect their willingness to donate. We found that teaching people about the risks of donating, decreasing costs related to donation, and raising awareness about it could increase the number of people willing to donate.

Organ Nonutilization Following Revision to the Public Health Service Donor Risk Criteria for HIV, HCV, or HBV Transmission.

BACKGROUND: Organs from Public Health Service criteria (PHSC) donors, previously referred to as PHS infectious-risk donors, have historically been recovered but not used, traditionally referred to as "discard," at higher rates despite negligible risk to recipients. On March 1, 2021, the definition of PHSC donors narrowed to include only the subset of donors deemed to have meaningfully elevated risk in the current era of improved infectious disease testing. METHODS: Using Scientific Registry of Transplant Recipients data from May 1, 2019, to December 31, 2022, we compared rates of PHSC classification and nonutilization of PHSC organs before versus after the March 1, 2021, policy change among recovered decedents using the χ 2 tests. We performed an adjusted interrupted time series analysis to examine kidney and liver recovery/nonuse (traditionally termed "discard") and kidney, liver, lung, and heart nonutilization (nonrecovery or recovery/nonuse) prepolicy versus postpolicy. RESULTS: PHSC classification dropped sharply from 24.5% prepolicy to 15.4% postpolicy ( P  < 0.001). Before the policy change, PHSC kidney recovery/nonuse, liver nonuse, lung nonuse, and heart nonuse were comparable to non-PHSC estimates (adjusted odds ratio: kidney =  0.98 1.06 1.14 , P  = 0.14; liver =  0.85 0.92 1.01 , P  = 0.07; lung =  0.91 0.99 1.08 , P  = 0.83; heart =  0.89 0.97 1.05 , P  = 0.47); following the policy change, PHSC kidney recovery/nonuse, liver nonuse, lung nonuse, and heart nonuse were lower than non-PHSC estimates (adjusted odds ratio: kidney =  0.77 0.84 0.91 , P  < 0.001; liver =  0.77 0.84 0.92 , P  < 0.001; lung =  0.74 0.81 0.90 , P  < 0.001; heart =  0.61 0.67 0.73 , P  < 0.001). CONCLUSIONS: Even though PHSC donors under the new definition are a narrower and theoretically riskier subpopulation than under the previous classification, PHSC status appears to be associated with a reduced risk of kidney and liver recovery/nonuse and nonutilization of all organs. Although historically PHSC organs have been underused, our findings demonstrate a notable shift toward increased PHSC organ utilization.

Augmenting the Unites States transplant registry with external mortality data: A moving target ripe for further improvement.

The Organ Procurement and Transplantation Network conducts a robust death verification process when augmenting the United States transplant registry with external sources of data. Process enhancements added over 35,000 externally verified deaths across waitlist candidates and transplant recipients for all organs beginning in April 2022. Ninety-four percent of added posttransplant deaths occurred beyond 5 years posttransplant, and over 74% occurred beyond 10 years. Deceased donor solid organ recipients transplanted from January 1, 2010, through October 31, 2020, were analyzed from January and July 2022 Organ Procurement and Transplantation Network Standard Transplant Analysis and Research and the Scientific Registry of Transplant Recipients Standard Analysis Files to quantify the impact of including vs excluding unverified deaths (not releasable to researchers) on posttransplant patient survival estimates. Across all organs, 1- and 5-year posttransplant survival rates were not substantially impacted; meaningful differences were observed in 10-year survival among kidney recipients. These findings bear important implications for anyone who utilized transplant registry data to examine long-term outcomes prior to the updated verification process. Users of transplant surveillance data should interpret results of long-term outcomes cautiously, particularly differences across subpopulations, and the transplant community should identify ways to improve data quality and minimize the reporting burden on transplant institutions.

Racial Disparities in Waiting List Outcomes of Patients Listed for Lung Transplantation.

BACKGROUND: The Lung Allocation Score, implemented in 2005, prioritized lung transplant candidates by medical urgency rather than waiting list time and was expected to improve racial disparities in transplant allocation. We evaluated whether racial disparities in lung transplant persisted after 2005. METHODS: We identified all wait-listed adult lung transplant candidates in the United States from 2005 through 2021 using the Scientific Registry of Transplant Recipients. We evaluated the association between race and receipt of a transplant by using a multivariable competing risk regression model adjusted for demographics, socioeconomic status, Lung Allocation Score, clinical measures, and time. We evaluated interactions between race and age, sex, socioeconomic status, and Lung Allocation Score. RESULTS: We identified 33,158 candidates on the lung transplant waiting list between 2005 and 2021: 27,074 White (82%), 3350 African American (10%), and 2734 Hispanic (8%). White candidates were older, had higher education levels, and had lower Lung Allocation Scores (P < .001). After multivariable adjustment, African American and Hispanic candidates were less likely to receive lung transplants than White candidates (African American: adjusted subhazard ratio, 0.86; 95% CI, 0.82-0.91; Hispanic: adjusted subhazard ratio, 0.82; 95% CI, 0.78-0.87). Lung transplant was significantly less common among Hispanic candidates aged >65 years (P = .003) and non-White candidates from higher-poverty communities (African-American: P = .013; Hispanic: P =.0036). CONCLUSIONS: Despite implementation of the Lung Allocation Score, racial disparities persisted for wait-listed African American and Hispanic lung transplant candidates and differed by age and poverty status. Targeted interventions are needed to ensure equitable access to this life-saving intervention.

Applying propensity methods to the United States transplant registry for external real-world evidence control arms for 5-year survival in the BENEFIT study.

To address the challenges of assessing the impact of a reasonably likely surrogate endpoint on long-term graft survival in prospective kidney transplant clinical trials, the Transplant Therapeutics Consortium established a real-world evidence workgroup evaluating the scientific value of using transplant registry data as an external control to supplement the internal control group. The United Network for Organ Sharing retrospectively simulated the use of several distinct contemporaneous external control groups, applied multiple cause inference methods, and compared treatment effects to those observed in the BENEFIT study. Applying BENEFIT study enrollment criteria produced a smaller historical cyclosporine control arm (n = 153) and a larger, alternative (tacrolimus) historical control arm (n = 1069). Following covariate-balanced propensity scoring, Kaplan-Meier 5-year all-cause graft survivals were 81.3% and 81.7% in the Organ Procurement and Transplantation Network (OPTN) tacrolimus and cyclosporine external control arms, similar to 80.3% observed in the BENEFIT cyclosporine treatment arm. Five-year graft survival in the belatacept-less intensive arm was significantly higher than the OPTN controls using propensity scoring for comparing cyclosporine and tacrolimus. Propensity weighting using OPTN controls closely mirrored the BENEFIT study's long-term control (cyclosporine) arm's survival rate and the less intensive arm's treatment effect (significantly higher survival vs control). This study supports the feasibility and validity of using supplemental external registry controls for long-term survival in kidney transplant clinical trials.

A2/A2B to B deceased donor kidney transplantation in the Kidney Allocation System era.

Kidney transplantation from blood type A2/A2B donors to type B recipients (A2→B) has increased dramatically under the current Kidney Allocation System (KAS). Among living donor transplant recipients, A2-incompatible transplants are associated with an increased risk of all-cause and death-censored graft failure. In light of this, we used data from the Scientific Registry of Transplant Recipients from December 2014 until June 2022 to evaluate the association between A2→B listing and time to deceased donor kidney transplantation (DDKT) and post-DDKT outcomes for A2→B recipients. Among 53 409 type B waitlist registrants, only 12.6% were listed as eligible to accept A2→B offers ("A2-eligible"). The rates of DDKT at 1-, 3-, and 5-years were 32.1%, 61.4%, and 72.1% among A2-eligible candidates and 14.1%, 29.9%, and 44.1% among A2-ineligible candidates, with the former experiencing a 133% higher rate of DDKT (Cox weighted hazard ratio (wHR) = 2.192.332.47; P < .001). The 7-year adjusted mortality was comparable between A2→B and B-ABOc (type B/O donors to B recipients) recipients (wHR 0.780.941.13, P = .5). Moreover, there was no difference between A2→B vs B-ABOc DDKT recipients with regards to death-censored graft failure (wHR 0.771.001.29, P > .9) or all-cause graft loss (wHR 0.820.961.12, P = .6). Following its broader adoption since the implementation of the kidney allocation system, A2→B DDKT appears to be a safe and effective transplant modality for eligible candidates. As such, A2→B listing for eligible type B candidates should be expanded.

The Independent Effects of Kidney Length and Vascular Plaque on Ten-Year Outcomes of Extended Criteria Donor Kidney Transplants.

The independent effects of deceased donor kidney length and vascular plaque on long-term graft survival are not established. Utilizing DonorNet attachments from 4,480 expanded criteria donors (ECD) recovered between 2008 and 2012 in the United States with at least one kidney biopsied and transplanted, we analyzed the relationship between kidney length and vascular plaques and 10-year hazard of all-cause graft failure (ACGF) using causal inference methods in a Cox regression framework. The composite plaque score (range 0-4) and the presence of any plaque (yes, no) was also analyzed. Kidney length was modeled both categorically (<10, 10-12, >12 cm) as well as numerically, using a restricted cubic spline to capture nonlinearity. Effects of a novel composite plaque score 4 vs. 0 (HR 1.08; 95% CI: 0.96, 1.23) and the presence of any vascular plaque (HR 1.08; 95% CI: 0.98, 1.20) were attenuated after adjustment. Likewise, we identified a potential nonlinear relationship between kidney length and the 10-year hazard of ACGF, however the strength of the relationship was attenuated after adjusting for other donor factors. The independent effects of vascular plaque and kidney length on long-term ECD graft survival were found to be minimal and should not play a significant role in utilization.

The association of donor hepatitis C virus infection with 3-year kidney transplant outcomes in the era of direct-acting antiviral medications.

To determine the effect of donor hepatitis C virus (HCV) infection on kidney transplant (KT) outcomes in the era of direct-acting antiviral (DAA) medications, we examined 68,087 HCV-negative KT recipients from a deceased donor between March 2015 and May 2021. A Cox regression analysis was used to estimate adjusted hazard ratios (aHRs) of KT failure, incorporating inverse probability of treatment weighting to control for patient selection to receive an HCV-positive kidney (either nucleic acid amplification test positive [NAT+, n = 2331] or antibody positive (Ab+)/NAT- [n = 1826]) based on recipient characteristics. Compared with kidney from HCV-negative donors, those from Ab+/NAT- (aHR = 0.91; 95% confidence interval [CI], 0.75-1.10) and HCV NAT+ (aHR = 0.89; 95% CI, 0.73-1.08) donors were not associated with an increased risk of KT failure over 3 years after transplant. Moreover, HCV NAT+ kidneys were associated with a higher 1-year estimated glomerular filtration (63.0 vs 61.0 mL/min/1.73 m2, P = .007) and lower risk of delayed graft function (aOR = 0.76; 95% CI, 0.68-0.84) compared with HCV-negative kidneys. Our findings suggest that donor HCV positivity is not associated with an elevated risk of graft failure. The inclusion of donor HCV status in the Kidney Donor Risk Index may no longer be appropriate in contemporary practice.

Beyond donation to organ utilization in the USA.

PURPOSE OF REVIEW: The deceased donor organ pool has broadened beyond young, otherwise healthy head trauma victims. But an abundance of donated organs only benefits patients if they are accepted, expeditiously transported and actually transplanted. This review focuses on postdonation challenges and opportunities to increase the number of transplants through improved organ utilization. RECENT FINDINGS: We build upon recently proposed changes in terminology for measuring organ utilization. Among organs recovered for transplant, the nonuse rate (NUR REC ) has risen above 25% for kidneys and pancreata. Among donors, the nonuse rate (NUR DON ) has risen to 40% for livers and exceeds 70% for thoracic organs. Programme-level variation in offer acceptance rates vastly exceeds variation in the traditional, 1-year survival benchmark. Key opportunities to boost utilization include donation after circulatory death and hepatitis C virus (HCV)+ organs; acute kidney injury and suboptimal biopsy kidneys; older and steatotic livers. SUMMARY: Underutilization of less-than-ideal, yet transplant-worthy organs remains an obstacle to maximizing the impact of the U.S. transplant system. The increased risk of inferior posttransplant outcomes must always be weighed against the risks of remaining on the waitlist. Advanced perfusion technologies; tuning allocation systems for placement efficiency; and data-driven clinical decision support have the potential to increase utilization of medically complex organs.

An experiment on the impact of predictive analytics on kidney offers acceptance decisions.

Because of the breadth of factors that might affect kidney transplant decisions to accept an organ or wait for another, presumably "better" offer, a high degree of heterogeneity in decision making exists among transplant surgeons and hospitals. These decisions do not typically include objective predictions regarding the future availability of equivalent or better-quality organs or the likelihood of patient death while waiting for another organ. To investigate the impact of displaying such predictions on organ donation decision making, we conducted a statistically designed experiment involving 53 kidney transplant professionals, in which kidney offers were presented via an online application and systematically altered to observe the effects on decision making. We found that providing predictive analytics for time-to-better offers and patient mortality improved decision consensus and decision-maker confidence in their decisions. Providing a visual display of the patient's mortality slope under accept/reject conditions shortened the time-to-decide but did not have an impact on the decision itself. Presenting the risk of death in a loss frame as opposed to a gain frame improved decision consensus and decision confidence. Patient-specific predictions surrounding future organ offers and mortality may improve decision quality, confidence, and expediency while improving organ utilization and patient outcomes.

Stakeholders' perspectives on transplant metrics: the 2022 Scientific Registry of Transplant Recipients' consensus conference.

In July 2022, the Scientific Registry of Transplant Recipients (SRTR) hosted an innovative, multistakeholder consensus conference to identify information and metrics desired by stakeholders in the transplantation system, including patients, living donors, caregivers, deceased donor family members, transplant professionals, organ procurement organization professionals, payers, and regulators. Crucially, patients, caregivers, living donors, and deceased donor family members were included in all aspects of this conference, including serving on the planning committee, participating in preconference focus groups and learning sessions, speaking at the conference, moderating conference sessions and breakout groups, and shaping the conclusions. Patients constituted 24% of the meeting participants. In this report, we document the proceedings and enumerate 160 recommendations, 10 of which have been highly prioritized. SRTR will use the recommendations to develop new presentations of information and metrics requested by stakeholders to support informed decision-making.

Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

Current opinions on DGF management practices: A survey of the United States and Canada.

INTRODUCTION: Significant center-to-center variation in attitudes and management of delayed graft function (DGF) remains common. METHODS: A survey to describe current DGF practices was developed by workgroup members sponsored by the National Kidney Foundation (NKF) and was distributed to both the NKF DGF workgroup members, kidney transplant program directors and the transplant community within the United States and Canada. Seventy-one percent of NKF workgroup members completed the survey along with 70 unique the United States and three Canadian kidney transplant programs. All Organ Procurement and Transplantation Network (OPTN) regions were represented. RESULTS: DGF was reported to occur at rate of 20%-40% for most centers with 3.9% indicating their incidence to be >60%. Most centers reported longer hospital lengths of stay and more frequent outpatient visits. Despite the commonality of DGF, only half of centers reported having an established protocol to manage DGF. Kidney allograft biopsies were the only consistent DGF management strategy observed, although use of machine perfusion was also heavily favored. Other DGF management strategies voiced by a minority included having established outpatient practices to care for DGF patients and administering outpatient community-based hemodialysis. CONCLUSION: Although approximately a third of survey responders indicated that risk of DGF played a role in their willingness to accept organs, most did not feel that increased cost or clinical impact on outcomes was a deterrent. Future strategies, including broader sharing of best practices, redefining terminology specific to DGF, the establishment of DGF dialysis guidelines and improving access to machine perfusion across OPOs may help reduce discard and improve utilization of kidneys at risk for DGF.

The real unmet need: A multifactorial approach for identifying sensitized kidney candidates with low access to transplant.

BACKGROUND: At the start of 2020, the kidney waiting list consisted of 2526 candidates with a calculated panel reactive antibody (CPRA) of 99.9% or greater, a cohort demonstrated in published research to have meaningfully lower than average access to transplantation even under the revised kidney allocation system (KAS). METHODS: This was a retrospective analysis of US kidney registrations using data from the OPTN [Reference (https://optn.transplant.hrsa.gov/data/about-data/)]. The period-prevalent study cohort consisted of US kidney-alone registrations who waited at least 1 day between April 1, 2016, when HLA DQ-Alpha and DP-Beta unacceptable antigen data became available in OPTN data collection, to December 31, 2019. Poisson rate regression was used to model deceased donor kidney transplant rates per active year waiting and using an offset term to account for differential at-risk periods. Median time to transplant was estimated for each IRR group using the Kaplan-Meier method. Sensitivity analyses were included to address geographic variation in supply-to-demand ratios and differences in dialysis time or waiting time. RESULTS: In this study, we found 1597 additional sensitized (CPRA 50-<99.9%) candidates with meaningfully lower than average access to transplant when simultaneously taking into account CPRA and other factors. In combination with CPRA, candidate blood type, Estimated Post-Transplant Survival Score (EPTS), and presence of other antibody specificities beyond those in the current, 5-locus CPRA were found to influence the likelihood of transplant. CONCLUSION: In total, this suggests approximately 4100 sensitized candidates are on the waiting list who represent a community of disadvantaged patients who may benefit from progressive therapies and interventions to facilitate incompatible transplantation. Though associated with higher risks, such interventions may nevertheless be more attractive than remaining on dialysis with the associated accumulation of mortality risk over time.