Genetically Modified Porcine Kidneys Have Sufficient Tissue Integrity for Use in Pig-to-Human Xenotransplantation.

OBJECTIVE: We sought to determine if genetically modified porcine kidneys used for xenotransplantation had sufficient tissue integrity to support long term function in a human recipient. BACKGROUND: Kidney transplantation remains the best available treatment for patients with end-stage kidney disease. However, a shortage of available donor human kidneys prevents many patients from achieving the benefits of transplantation. Xenotransplantation is a potential solution to this shortage. Recent pre-clinical human studies have demonstrated kidneys from genetically modified pig donors can be transplanted without hyperacute rejection and capable of providing creatinine and other solute clearance. It is unknown whether the porcine kidneys would tolerate the relatively higher resting blood pressure in an adult human recipient compared to the pig donor or non-human primate (NHP) recipients used in translational studies. Furthermore, previous experience in NHPs raised concerns about the tissue integrity of the porcine ureter and post-xenotransplant growth of the porcine kidney. METHODS: Kidneys recovered from porcine donors with 10 gene edits were transplanted into decedent brain dead recipients who were not eligible for organ donation. Decedents underwent bilateral native nephrectomy prior to transplant and were followed for 3-7 days. Standard induction and maintenance immunosuppression was used as previously reported. Vital signs including blood pressure were recorded frequently. Kidney xenografts were assessed daily, serially biopsied, and were measured at implantation and study completion. RESULTS: Three decedents underwent successful xenotransplantation. Subcapsular hematomas developed requiring incision of the xenograft capsules to prevent Page kidney. Blood pressures were maintained in a physiologic range for adult humans (median arterial pressures (MAP) 108.5mmHg (Interquartile Range (IQR): 97-114mmHg), 74mmHg (IQR: 71-78mmHg), and 95mmHg (IQR: 88-99mmHg. respectively) and no bleeding complications or aneurysm formation was observed. Serial biopsies were taken from the xenografts without apparent loss of tissue integrity, despite the lack of a capsule. Ureteroneocystotomies remained intact without evidence of urine leak. Xenograft growth was observed, but plateaued, in 1 decedent with increased volume of the left and right xenografts by 25% and 26%, respectively, and in the context of human growth hormone levels consistently less <0.1 ng/ml and insulin-like growth factor 1 levels ranging from 34-50 ng/ml. CONCLUSIONS: The findings of this study suggest kidneys from 10-gene edited porcine donors have sufficient tissue integrity to tolerate xenotransplantation into a living human recipient. There was no evidence of anastomotic complications and the xenografts tolerated needle biopsy without issue. Xenograft growth occurred but plateaued by study end; further observation and investigation will be required to confirm this finding and elucidate underlying mechanisms.

Liver Transplant Costs and Activity After United Network for Organ Sharing Allocation Policy Changes.

Importance: A new liver allocation policy was implemented by United Network for Organ Sharing (UNOS) in February 2020 with the stated intent of improving access to liver transplant (LT). There are growing concerns nationally regarding the implications this new system may have on LT costs, as well as access to a chance for LT, which have not been captured at a multicenter level. Objective: To characterize LT volume and cost changes across the US and within specific center groups and demographics after the policy implementation. Design, Setting, and Participants: This cross-sectional study collected and reviewed LT volume from multiple centers across the US and cost data with attention to 8 specific center demographics. Two separate 12-month eras were compared, before and after the new UNOS allocation policy: March 4, 2019, to March 4, 2020, and March 5, 2020, to March 5, 2021. Data analysis was performed from May to December 2022. Main Outcomes and Measures: Center volume, changes in cost. Results: A total of 22 of 68 centers responded comparing 1948 LTs before the policy change and 1837 LTs postpolicy, resulting in a 6% volume decrease. Transplants using local donations after brain death decreased 54% (P < .001) while imported donations after brain death increased 133% (P = .003). Imported fly-outs and dry runs increased 163% (median, 19; range, 1-75, vs 50, range, 2-91; P = .009) and 33% (median, 3; range, 0-16, vs 7, range, 0-24; P = .02). Overall hospital costs increased 10.9% to a total of $46 360 176 (P = .94) for participating centers. There was a 77% fly-out cost increase postpolicy ($10 600 234; P = .03). On subanalysis, centers with decreased LT volume postpolicy observed higher overall hospital costs ($41 720 365; P = .048), and specifically, a 122% cost increase for liver imports ($6 508 480; P = .002). Transplant centers from low-income states showed a significant increase in hospital (12%) and import (94%) costs. Centers serving populations with larger proportions of racial and ethnic minority candidates and specifically Black candidates significantly increased costs by more than 90% for imported livers, fly-outs, and dry runs despite lower LT volume. Similarly, costs increased significantly (>100%) for fly-outs and dry runs in centers from worse-performing health systems. Conclusions and Relevance: Based on this large multicenter effort and contrary to current assumptions, the new liver distribution system appears to place a disproportionate burden on populations of the current LT community who already experience disparities in health care. The continuous allocation policies being promoted by UNOS could make the situation even worse.

Inhibition of NFAT promotes loss of tissue resident uterine natural killer cells and attendant pregnancy complications in humans.

Uterine natural killer cells (uNKs) are a tissue resident lymphocyte population that are critical for pregnancy success. Although mouse models have demonstrated that NK deficiency results in abnormal placentation and poor pregnancy outcomes, the generalizability of this knowledge to humans remains unclear. Here we identify uterus transplant (UTx) recipients as a human population with reduced endometrial NK cells and altered pregnancy phenotypes. We further show that the NK reduction in UTx is due to impaired transcriptional programming of NK tissue residency due to blockade of the transcription factor nuclear factor of activated T cells (NFAT). NFAT-dependent genes played a role in multiple molecular circuits governing tissue residency in uNKs, including early residency programs involving AP-1 transcription factors as well as TGFß-mediated upregulation of surface integrins. Collectively, our data identify a previously undescribed role for NFAT in uterine NK tissue residency and provide novel mechanistic insights into the biologic basis of pregnancy complications due to alteration of tissue resident NK subsets in humans. One Sentence Summary: Role of NFAT in uterine NK cell tissue residency.

Spatiotemporal immune atlas of a clinical-grade gene-edited pig-to-human kidney xenotransplant.

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. Here, we transplant a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and study the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells are uncommon in the porcine kidney cortex early after xenotransplantation and consist of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages express genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft is detectable. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression may be able to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

Physiologic homeostasis after pig-to-human kidney xenotransplantation.

Demand for kidney grafts outpaces supply, limiting kidney transplantation as a treatment for kidney failure. Xenotransplantation has the potential to make kidney transplantation available to many more patients with kidney failure, but the ability of xenografts to support human physiologic homeostasis has not been established. A brain-dead adult decedent underwent bilateral native nephrectomies followed by 10 gene-edited (four gene knockouts, six human transgenes) pig-to-human xenotransplantation. Physiologic parameters and laboratory values were measured for seven days in a critical care setting. Data collection aimed to assess homeostasis by measuring components of the renin-angiotensin-aldosterone system, parathyroid hormone signaling, glomerular filtration rate, and markers of salt and water balance. Mean arterial blood pressure was maintained above 60 mmHg throughout. Pig kidneys secreted renin (post-operative day three to seven mean and standard deviation: 47.3 ± 9 pg/mL). Aldosterone and angiotensin II levels were present (post-operative day three to seven, 57.0 ± 8 pg/mL and 5.4 ± 4.3 pg/mL, respectively) despite plasma renin activity under 0.6 ng/mL/hr. Parathyroid hormone levels followed ionized calcium. Urine output down trended from 37 L to 6 L per day with 4.5 L of electrolyte free water loss on post-operative day six. Aquaporin 2 channels were detected in the apical surface of principal cells, supporting pig kidney response to human vasopressin. Serum creatinine down trended to 0.9 mg/dL by day seven. Glomerular filtration rate ranged 90-240 mL/min by creatinine clearance and single-dose inulin clearance. Thus, in a human decedent model, xenotransplantation of 10 gene-edited pig kidneys provided physiologic balance for seven days. Hence, our in-human study paves the way for future clinical study of pig-to-human kidney xenotransplantation in living persons.

Health Inequity in Likelihood and Time to Renal Recovery after Living Kidney Donation: Implications for Kidney Health in Black Americans.

BACKGROUND: Live donor kidney transplantation has been popularized to help mitigate the organ shortage crisis. At the time of living donor nephrectomy, living donors lose 50% of their kidney function or glomerular filtration rate (GFR). Studies have shown that in healthy living donors, the remaining kidney is able to adapt and recover 10% to 25% of postdonation lost GFR. GFR recovery is critical to long-term kidney health, particularly for Black Americans who disproportionately suffer from kidney disease with an incidence 2.5 times White Americans. To date, no study has examined whether health inequities in renal recovery postdonation exist. STUDY DESIGN: We retrospectively analyzed 100,121 living kidney donors reported to the Scientific Registry of Transplant Recipients between 1999 and 2021. We estimated GFR (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration 2021 equation and predicted the likelihood (logistic regression) and time (Cox regression) to recovery of 60% and 75% predonation eGFR. Models adjusted for age, sex, race, BMI, and predonation eGFR. RESULTS: Black patients were 47% (adjusted odds ratio 0.53, 95% CI 0.50 to 0.56, p < 0.001) and 43% (adjusted odds ratio 0.57, 95% CI 0.54 to 0.60, p < 0.001) less likely to recover 60% and 75% of predonation eGFR, respectively, compared with their White counterparts. The hazard ratio for time to renal recovery of 60% and 75% of predonation eGFR was 22% (adjusted hazard ratio 0.78, 95% CI 0.76 to 0.80, p < 0.001) and 38% (adjusted hazard ratio 0.62, 95% CI 0.60 to 0.65, p < 0.001) lower, respectively, than White patients. CONCLUSIONS: Black living kidney donors were less likely to recover predonation eGFR, and time to renal recovery was significantly longer than their White counterparts. These data highlight the need for enhanced living kidney donor follow-up, particularly for Black living kidney donors who are at greatest future risk of end-stage kidney disease.

Treatment of Hypercalcemic Hyperparathyroidism After Kidney Transplantation Is Associated With Improved Allograft Survival.

BACKGROUND: Hyperparathyroidism (HPT) and malignancy are the most common causes of hypercalcemia. Among kidney transplant (KT) recipients, hypercalcemia is mostly caused by tertiary HPT. Persistent tertiary HPT after KT is associated with allograft failure. Previous studies on managing tHPT were subjected to survivor treatment selection bias; as such, the impact of tertiary HPT treatment on allograft function remained unclear. We aim to assess the association between hypercalcemic tertiary HPT treatment and kidney allograft survival. MATERIALS AND METHODS: We identified 280 KT recipients (2015-2019) with elevated post-KT adjusted serum calcium and parathyroid hormone (PTH). KT recipients were characterized by treatment: cinacalcet, parathyroidectomy, or no treatment. Time-varying Cox regression with delayed entry at the time of first elevated post-KT calcium was conducted, and death-censored and all-cause allograft failure were compared by treatment groups. RESULTS: Of the 280 recipients with tHPT, 49 underwent PTx, and 98 received cinacalcet. The median time from KT to first elevated calcium was 1 month (IQR: 0-4). The median time from first elevated calcium to receiving cinacalcet and parathyroidectomy was 0(IQR: 0-3) and 13(IQR: 8-23) months, respectively. KT recipients with no treatment had shorter dialysis vintage (P = .017) and lower PTH at KT (P = .002), later onset of hypercalcemia post-KT (P < .001). Treatment with PTx (adjusted hazard ratio (aHR) = 0.18, 95%CI 0.04-0.76, P = .02) or cinacalcet (aHR = 0.14, 95%CI 0.004-0.47, P = .002) was associated with lower risk of death-censored allograft failure. Moreover, receipt of PTx (aHR = 0.28, 95%CI 0.12-0.66, P < .001) or cinacalcet (aHR = 0.38, 95%CI 0.22-0.66, P < .001) was associated with lower risk of all-cause allograft failure. CONCLUSIONS: This study demonstrates that treatment of hypercalcemic tertiary HPT post-KT is associated with improved allograft survival. Although these findings are not specific to hypercalcemia of malignancy, they do demonstrate the negative impact of hypercalcemic tertiary HPT on kidney function. Hypercalcemic HPT should be screened and aggressively treated post-KT.

Regional Social Vulnerability is Associated With Geographic Disparity in Waitlist Outcomes for Patients With Non-Hepatocellular Carcinoma Model for End-stage Liver Disease Exceptions in the United States.

OBJECTIVE: This study was undertaken to evaluate the role of regional social vulnerability in geographic disparity for patients listed for liver transplantation with non-hepatocellular carcinoma (HCC) model for end-stage liver disease (MELD) exceptions. SUMMARY AND BACKGROUND: Prior work has demonstrated regional variability in the appropriateness of MELD exceptions for diagnoses other than HCC. METHODS: Adults listed at a single center for first-time liver-only transplantation without HCC after June 18, 2013 in the Scientific Registry of Transplant Recipients database as of March 2021 were examined. Candidates were mapped to hospital referral regions (HRRs). Adjusted likelihood of mortality and liver transplantation were modeled. Advantaged HRRs were defined as those where exception patients were more likely to be transplanted, yet no more likely to die in adjusted analysis. The Centers for Disease Control's Social Vulnerability Index (SVI) was used as the measure for community health. Higher SVIs indicate poorer community health. RESULTS: There were 49,494 candidates in the cohort, of whom 4337 (8.8%) had MELD exceptions. Among continental US HRRs, 27.3% (n = 78) were identified as advantaged. The mean SVI of advantaged HRRs was 0.42 versus 0.53 in nonadvantaged HRRs ( P = 0.002), indicating better community health in these areas. Only 25.3% of advantaged HRRs were in spatial clusters of high SVI versus 40.7% of nonadvantaged HRRs, whereas 44.6% of advantaged HRRs were in spatial clusters of low SVI versus 38.0% of nonadvantaged HRRs ( P = 0.037). CONCLUSIONS: An advantage for non-HCC MELD exception patients is associated with lower social vulnerability on a population level. These findings suggest assigning similar waitlist priority to all non-HCC exception candidates without considering geographic differences in social determinants of health may actually exacerbate rather than ameliorate disparity.

Treatment Location Variation for Chronic Limb-Threatening Ischemia in Patients With Kidney Failure.

INTRODUCTION: End-stage kidney disease (ESKD) is an established risk factor for chronic limb-threatening ischemia (CLTI). Procedural location for ESKD patients has not been well described. This study aims to examine variation in index procedural location in ESKD versus non-ESKD patients undergoing peripheral vascular intervention for CLTI and identify preoperative risk factors for tibial interventions. METHODS: Chronic limb-threatening ischemia (CLTI) patients were identified in the Vascular Quality Initiative (VQI) peripheral vascular intervention dataset. Patient demographics and comorbidities were compared between patients with and without ESKD and those undergoing index tibial versus nontibial interventions. A multivariable logistic regression evaluating risk factors for tibial intervention was conducted. RESULTS: A total of 23,480 procedures were performed on CLTI patients with 13.6% (n = 3154) with ESKD. End-stage kidney disease (ESKD) patients were younger (66.56 ± 11.68 versus 71.66 ± 12.09 y old, P = 0.019), more often Black (40.6 versus 18.6%, P < 0.001), male (61.2 versus 56.5%, P < 0.001), and diabetic (81.8 versus 60.0%, P < 0.001) than non-ESKD patients. Patients undergoing index tibial interventions had higher rates of ESKD (19.4 versus 10.6%, P < 0.001) and diabetes (73.4 versus 57.5%, P < 0.001) and lower rates of smoking (49.9 versus 73.0%, P < 0.001) than patients with nontibial interventions. ESKD (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.52-1.86, P < 0.001), Black race (OR 1.19, 95% CI 1.09-1.30, P < 0.001), and diabetes (OR 1.82, 95% CI 1.71-2.00, P < 0.001) were risk factors for tibial intervention. CONCLUSIONS: Patients with ESKD and CLTI have higher rates of diabetes and tibial disease and lower rates of smoking than non-ESKD patients. Tibial disease was associated with ESKD, diabetes, and Black race.

Mitigating Health Disparities in Transplantation Requires Equity, Not Equality.

Despite decades of research and evidence-based mitigation strategies, disparities in access to transplantation persist for all organ types and in all stages of the transplant process. Although some strategies have shown promise for alleviating disparities, others have fallen short of the equity goal by providing the same tools and resources to all rather than tailoring the tools and resources to one's circumstances. Innovative solutions that engage all stakeholders are needed to achieve equity regardless of race, sex, age, socioeconomic status, or geography. Mitigation of disparities is paramount to ensure fair and equitable access for those with end-stage disease and to preserve the trust of the public, upon whom we rely for their willingness to donate organs. In this overview, we present a summary of recent literature demonstrating persistent disparities by stage in the transplant process, along with policies and interventions that have been implemented to combat these disparities and hypotheses for why some strategies have been more effective than others. We conclude with future directions that have been proposed by experts in the field and how these suggested strategies may help us finally arrive at equity in transplantation.

Quantifying the association of individual-level characteristics with disparities in kidney transplant waitlist addition among people with HIV.

BACKGROUND: Over 45% of people with HIV (PWH) in the United States at least 50 years old and are at heightened risk of aging-related comorbidities including end-stage kidney disease (ESKD), for which kidney transplant is the optimal treatment. Among ESKD patients, PWH have lower likelihood of waitlisting, a requisite step in the transplant process, than individuals without HIV. It is unknown what proportion of the inequity by HIV status can be explained by demographics, medical characteristics, substance use history, and geography. METHODS: The United States Renal Data System, a national database of all individuals ESKD, was used to create a cohort of people with and without HIV through Medicare claims linkage (2007-2017). The primary outcome was waitlisting. Inverse odds ratio weighting was conducted to assess what proportion of the disparity by HIV status could be explained by individual characteristics. RESULTS: Six thousand two hundred and fifty PWH were significantly younger at ESKD diagnosis and more commonly Black with fewer comorbidities. PWH were more frequently characterized as using tobacco, alcohol and drugs. Positive HIV-status was associated with 57% lower likelihood of waitlisting [adjusted hazard ratio (aHR): 0.43, 95% confidence interval (CI): 0.46-0.48, P  < 0.001]. Controlling for demographics, medical characteristics, substance use and geography explained 39.8% of this observed disparity (aHR: 0.69, 95% CI: 0.59-0.79, P  < 0.001). CONCLUSION: PWH were significantly less likely to be waitlisted, and 60.2% of that disparity remained unexplained. HIV characteristics such as CD4 + counts, viral loads, antiretroviral therapy adherence, as well as patient preferences and provider decision-making warrant further study.

Interpersonal Connections Are Important for Virtual Kidney Transplant Educational Program Development.

Introduction: The Living Donor Navigator program is designed to mitigate disparities in living donor kidney transplantation, although geographic disparities in program participation were observed in the initial years of implementation. The purpose of this study was to understand participant perspectives regarding the use of a virtual option/alternative to expand program participation. Methods: Previous participants of the in-person navigator program were purposively sampled. Using the nominal group technique, a well-structured formative methodology to elicit participant perspectives, 2 meetings were conducted among transplant recipients and advocates (N = 13) to identify and prioritize responses to the question "What things would concern you about participating in a virtual and remote Living Donor Navigator program?" Findings: Mean participant age was 59.3 (9.3) years, and participants were 54% male and 62% white. Education levels varied from less than high school to master's degrees. Participants generated 70 unique responses, of which 36 (51.4%) received prioritization. The top 5 ranked responses of each nominal group technique meeting received approximately 50 percent (47.6% vs. 66.7%, respectively) of the total votes and described the potentially limited interpersonal connections, time conflicts, and differing content in a virtual navigator program compared to the in-person model. Discussion: These data suggest that previous participants were concerned with upholding the original design of the program, thus, virtual living donor kidney transplantation programs should aim to maintain interpersonal connections and consistency of content to ensure adequate programmatic engagement. Future research will focus on program fidelity independent of delivery modality.

HRSA's Patient-Centric Approach to Modernizing the US Transplant System.

This Viewpoint discusses the benefits of modernization efforts for the US transplant system.

African American/Black race, apolipoprotein L1 , and serum creatinine among persons with HIV.

OBJECTIVE: Accurate estimation of kidney function is critical among persons with HIV (PWH) to avoid under-dosing of antiretroviral therapies and ensure timely referral for kidney transplantation. Existing estimation equations for kidney function include race, the appropriateness of which has been debated. Given advancements in understanding of race and the necessity of accuracy in kidney function estimation, this study aimed to examine whether race, or genetic factors, improved prediction of serum creatinine among PWH. DESIGN: This cross-sectional study utilized data from the Center for AIDS Research Network of Integrated Clinical Systems cohort (2008-2018). The outcome was baseline serum creatinine. METHODS: Ordinary least squares regression was used to examine whether inclusion of race or genetic factors [ apolipoprotein-L1 ( APOL1 ) variants and genetic African ancestry] improved serum creatinine prediction. A reduction in root mean squared error (RMSE) greater than 2% was a clinically relevant improvement in predictive ability. RESULTS: There were 4183 PWH included. Among PWH whose serum creatinine was less than 1.7 mg/dl, race was significantly associated with serum creatinine ( ß â€Š= 0.06, SE = 0.01, P  < 0.001) but did not improve predictive ability. African ancestry and APOL1 variants similarly failed to improve predictive ability. Whereas, when serum creatinine was at least 1.7 mg/dl, inclusion of race reduced the RMSE by 2.1%, indicating improvement in predictive ability. APOL1 variants further improved predictive ability by reducing the RMSE by 2.9%. CONCLUSION: These data suggest that, among PWH, inclusion of race or genetic factors may only be warranted at higher serum creatinine levels. Work eliminating existing healthcare disparities while preserving the utility of estimating equations is needed.

Normal Graft Function After Pig-to-Human Kidney Xenotransplant.

This case series examines the ability of a pig-to-human xenograft to provide life-sustaining kidney function.

Non-invasive evaluation of hepatic macrosteatosis in deceased donors.

INTRODUCTION: Liver allocation changes have led to increased travel and expenditures, highlighting the need to efficiently identify marginal livers suitable for transplant. We evaluated the validity of existing non-invasive liver quality tests and a novel machine learning-based model at predicting deceased donor macrosteatosis >30%. METHODS: We compared previously-validated non-invasive tests and a novel machine learning-based model to biopsies in predicting macrosteatosis >30%. We also tested them in populations enriched for macrosteatosis. RESULTS: The Hepatic Steatosis Index area-under-the-curve (AUC) was 0.56. At the threshold identified by Youden's J statistic, sensitivity, specificity, positive, and negative predictive values were 49.6%, 58.9%, 14.0%, and 89.7%. Other tests demonstrated comparable results. Machine learning produced the highest AUC (0.71). Even in populations enriched for macrosteatosis, no test was sufficiently predictive. CONCLUSION: Commonly used clinical scoring systems and a novel machine learning-based model were not clinically useful, highlighting the importance of pre-procurement biopsies to facilitate allocation.

Racial Disparities in Access to the Kidney Transplant Waitlist Among People with Human Immunodeficiency Virus.

The epidemiology of human immunodeficiency virus (HIV) has shifted such that Black individuals disproportionately represent incident HIV diagnoses. While risk of end-stage kidney disease (ESKD) among people with HIV (PWH) has declined with effective antiretroviral therapies, a substantial racial disparity in ESKD burden exists with the greatest prevalence among Black PWH. Disparities in waitlisting for kidney transplantation, the optimal treatment for ESKD, exist for both PWH and Black individuals without HIV, but it is unknown whether these characteristics together exacerbate such disparities. Six hundred two thousand six ESKD patients were identified from the United States Renal Data System (January 1, 2007 to December 31, 2017), and HIV-status was determined through Medicare claims. Cox proportional hazards regression was used to determine waitlisting rates. Multiplicative interaction terms between HIV-status and race were examined. The 6250 PWH were significantly younger, more commonly Black, and less commonly female than those without HIV. HIV-status and race were independently associated with 50% and 12% lower likelihood of waitlisting, respectively [adjusted hazard ratio (aHR): 0.50, 95% confidence interval (CI): 0.36-0.69, p < 0.001; aHR: 0.88, 95% CI: 0.87-0.90, p < 0.001]. There was also a significant interaction present between HIV-status and Black race (aHR: 0.80, 95% CI: 0.66-0.98, p < 0.001) such that, while HIV-status and Black race were independently associated with decreased waitlisting, the interaction of Black race and HIV-status exacerbated those disparities. While limited by lack of HIV-specific data that may impact inferences with respect to race, additional studies are urgently needed to understand the interplay between HIV risk factors, HIV-stigma, and racism, and how intersectionality may exacerbate disparities in transplantation among PWH.

Social network interventions to reduce race disparities in living kidney donation: Design and rationale of the friends and family of kidney transplant patients study (FFKTPS).

INTRODUCTION: Racial/ethnic disparities in living donor kidney transplantation (LDKT) are a persistent challenge. Although nearly all directed donations are from members of patients' social networks, little is known about which social network members take steps toward living kidney donation, which do not, and what mechanisms contribute to racial/ethnic LDKT disparities. METHODS: We describe the design and rationale of the Friends and Family of Kidney Transplant Patients Study, a factorial experimental fielding two interventions designed to promote LKD discussions. Participants are kidney transplant candidates at two centers who are interviewed and delivered an intervention by trained center research coordinators. The search intervention advises patients on which social network members are most likely to be LKD contraindication-free; the script intervention advises patients on how to initiate effective LKD discussions. Participants are randomized into four conditions: no intervention, search only, script only, or both search and script. Patients also complete a survey and optionally provide social network member contact information so they can be surveyed directly. This study will seek to enroll 200 transplant candidates. The primary outcome is LDKT receipt. Secondary outcomes include live donor screening and medical evaluations and outcomes. Tertiary outcomes include LDKT self-efficacy, concerns, knowledge, and willingness, measured before and after the interventions. CONCLUSION: This study will assess the effectiveness of two interventions to promote LKD and ameliorate Black-White disparities. It will also collect unprecedented information on transplant candidates' social network members, enabling future work to address network member structural barriers to LKD.