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A Metabolomics Approach to Identify Metabolites Associated With Mortality in Patients Receiving Maintenance Hemodialysis

Al Awadhi, Solaf; Myint, Leslie; Guallar, Eliseo; Clish, Clary B; Wulczyn, Kendra E; Kalim, Sahir; Thadhani, Ravi; Segev, Dorry L; McAdams DeMarco, Mara; Moe, Sharon M; Moorthi, Ranjani N; Hostetter, Thomas H; Himmelfarb, Jonathan; Meyer, Timothy W; Powe, Neil R; Tonelli, Marcello; Rhee, Eugene P; Shafi, Tariq
INTRODUCTION/UNASSIGNED:Uremic toxins contributing to increased risk of death remain largely unknown. We used untargeted metabolomics to identify plasma metabolites associated with mortality in patients receiving maintenance hemodialysis. METHODS/UNASSIGNED:We measured metabolites in serum samples from 522 Longitudinal US/Canada Incident Dialysis (LUCID) study participants. We assessed the association between metabolites and 1-year mortality, adjusting for age, sex, race, cardiovascular disease, diabetes, body mass index, serum albumin, Kt/Vurea, dialysis duration, and country. We modeled these associations using limma, a metabolite-wise linear model with empirical Bayesian inference, and 2 machine learning (ML) models: Least absolute shrinkage and selection operator (LASSO) and random forest (RF). We accounted for multiple testing using a false discovery rate (pFDR) adjustment. We defined significant mortality-metabolite associations as pFDR < 0.1 in the limma model and metabolites of at least medium importance in both ML models. RESULTS/UNASSIGNED:limma. CONCLUSION/UNASSIGNED:Quinolinate and mesaconate were significantly associated with a 1-year risk of death in incident patients receiving maintenance hemodialysis. External validation of our findings is needed.
PMCID:11403082
PMID: 39291216
ISSN: 2468-0249
CID: 5720942

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

Kaplow, Katya; Ruck, Jessica M; Levan, Macey L; Thomas, Alvin G; Stewart, Darren; Massie, Allan B; Sung, Hannah C; Pisano, Sarah F; Sidoti, Carolyn; Segev, Dorry L; Sinacore, Joseph; Waterman, Amy D
RATIONALE & OBJECTIVE/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:We surveyed 802 US adults (aged 25-65 years) in June 2021, randomly selected from an online platform with diverse representation. ANALYTICAL APPROACH/UNASSIGNED:and Fisher exact tests. We inductively evaluated free-text responses to identify additional barriers and facilitators to living kidney donation. RESULTS/UNASSIGNED: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/UNASSIGNED:Potential for selection bias resulting from the use of survey panels and varied incentive amounts, and measurement error related to respondents' attention level. CONCLUSIONS/UNASSIGNED: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.
PMCID:10906424
PMID: 38435064
ISSN: 2590-0595
CID: 5723042

A Delphi Panel Study for Public Education about Vascularized Composite Allograft Donation in the United States

Downey, Max C; Sidoti, Carolyn N; Ferzola, Alexander; Anderson, Naomi; Sung, Hannah C; Van Pilsum Rasmussen, Sarah E; Vanterpool, Karen B; Segev, Dorry L; Cooney, Carisa M; Kimberly, Laura L; Warren, Daniel S; Johnson, Ieesha D; Brandacher, Gerald; Gordon, Elisa J; Levan, Macey L
PMID: 39095046
ISSN: 2164-6708
CID: 5713992

Rapid Wane and Recovery of XBB Sublineage Neutralization After Sequential Omicron-based Vaccination in Solid Organ Transplant Recipients

Johnston, Trevor S; Hage, Camille; Abedon, Aura T; Panda, Snigdha; Alejo, Jennifer L; Eby, Yolanda; Segev, Dorry L; Tobian, Aaron A R; Cox, Andrea L; Werbel, William A; Karaba, Andrew H
Durability of variant neutralization in solid organ transplant recipients following Omicron-containing boosters is unknown. We report wane in XBB.1.5 neutralization by 3 months following a first bivalent booster, improved by a second booster; hybrid immunity improved peak, and duration of neutralization. Boosting at 3 to 6 months appears necessary to maintain neutralization.
PMCID:11426267
PMID: 38953683
ISSN: 1537-6591
CID: 5713902

ChatGPT Solving Complex Kidney Transplant Cases: A Comparative Study With Human Respondents

Mankowski, Michal A; Jaffe, Ian S; Xu, Jingzhi; Bae, Sunjae; Oermann, Eric K; Aphinyanaphongs, Yindalon; McAdams-DeMarco, Mara A; Lonze, Bonnie E; Orandi, Babak J; Stewart, Darren; Levan, Macey; Massie, Allan; Gentry, Sommer; Segev, Dorry L
INTRODUCTION/BACKGROUND:ChatGPT has shown the ability to answer clinical questions in general medicine but may be constrained by the specialized nature of kidney transplantation. Thus, it is important to explore how ChatGPT can be used in kidney transplantation and how its knowledge compares to human respondents. METHODS:We prompted ChatGPT versions 3.5, 4, and 4 Visual (4 V) with 12 multiple-choice questions related to six kidney transplant cases from 2013 to 2015 American Society of Nephrology (ASN) fellowship program quizzes. We compared the performance of ChatGPT with US nephrology fellowship program directors, nephrology fellows, and the audience of the ASN's annual Kidney Week meeting. RESULTS:Overall, ChatGPT 4 V correctly answered 10 out of 12 questions, showing a performance level comparable to nephrology fellows (group majority correctly answered 9 of 12 questions) and training program directors (11 of 12). This surpassed ChatGPT 4 (7 of 12 correct) and 3.5 (5 of 12). All three ChatGPT versions failed to correctly answer questions where the consensus among human respondents was low. CONCLUSION/CONCLUSIONS:Each iterative version of ChatGPT performed better than the prior version, with version 4 V achieving performance on par with nephrology fellows and training program directors. While it shows promise in understanding and answering kidney transplantation questions, ChatGPT should be seen as a complementary tool to human expertise rather than a replacement.
PMCID:11441623
PMID: 39329220
ISSN: 1399-0012
CID: 5714092

Safety of Kidney Transplantation from Donors with HIV

Durand, Christine M; Massie, Allan; Florman, Sander; Liang, Tao; Rana, Meenakshi M; Friedman-Moraco, Rachel; Gilbert, Alexander; Stock, Peter; Mehta, Sapna A; Mehta, Shikha; Stosor, Valentina; Pereira, Marcus R; Morris, Michele I; Hand, Jonathan; Aslam, Saima; Malinis, Maricar; Haidar, Ghady; Small, Catherine B; Santos, Carlos A Q; Schaenman, Joanna; Baddley, John; Wojciechowski, David; Blumberg, Emily A; Ranganna, Karthik; Adebiyi, Oluwafisayo; Elias, Nahel; Castillo-Lugo, Jose A; Giorgakis, Emmanouil; Apewokin, Senu; Brown, Diane; Ostrander, Darin; Eby, Yolanda; Desai, Niraj; Naqvi, Fizza; Bagnasco, Serena; Watson, Natasha; Brittain, Erica; Odim, Jonah; Redd, Andrew D; Tobian, Aaron A R; Segev, Dorry L; ,
BACKGROUND:Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. METHODS:In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. RESULTS:We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. CONCLUSIONS:In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.).
PMID: 39413376
ISSN: 1533-4406
CID: 5711682

Thirty-Year Trends in Perioperative Mortality Risk for Living Kidney Donors

Massie, Allan B; Motter, Jennifer D; Snyder, Jon J; Levan, Macey L; Segev, Dorry L
PMID: 39196582
ISSN: 1538-3598
CID: 5711412

Patient Perspectives on the Use of Aging Metrics for Kidney Transplant Decision-Making

Nalatwad, Akanksha; Quint, Evelien E; Fazal, Maria; Thompson, Valerie; Chen, Xiaomeng; Shrestha, Prakriti; Van Pilsum Rasmussen, Sarah E; Li, Yiting; Segev, Dorry L; Humbyrd, Casey Jo; McAdams-DeMarco, Mara
INTRODUCTION/BACKGROUND:Frailty and cognitive function are often measured during kidney transplant evaluation. However, patient perspectives on the ethical considerations of this practice are unclear. RESEARCH QUESTION/OBJECTIVE:What are patient perspectives on the use of aging metrics in kidney transplant decision-making? DESIGN/METHODS:One hundred participants who were evaluated for kidney transplantation and were enrolled in an ongoing prospective cohort study (response rate = 61.3%) were surveyed. Participants were informed of the definitions of frailty and cognitive impairment and then asked survey questions regarding the use of these measures of aging to determine kidney transplant candidacy. RESULTS:Participants (75.6%) thought it was unfair to prevent older adults from receiving a kidney transplant based on age, but there was less agreement on whether it was fair to deny frail (46.5%) and cognitively impaired (45.9%) patients from accessing kidney transplantation. Compared to older participants, younger participants had 5.36-times (95%CI:1.94-14.81) the odds of choosing a hypothetical younger, frail patient to list for kidney transplantation than an older, non-frail patient; they also had 3.56-times (95%CI:1.33-9.56) the odds of choosing the hypothetical frail patient with social support rather than a non-frail patient without social support. Participants disagreed on the use of patient age as a listing criterion; 19.5% ranked it as the fairest and 28.7% as the least fair. CONCLUSION/CONCLUSIONS:The patient views highlighted in this study are an important step toward developing ethical guidelines to ensure fair use of frailty, cognitive function, and chronological age for kidney transplant decision-making.
PMCID:11449634
PMID: 39105243
ISSN: 2164-6708
CID: 5706732

Center and Individual Willingness to Consider Heart and Lung Offers From Donors With Hepatitis C

Ruck, Jessica M; Bowring, Mary G; Zeiser, Laura B; Durand, Christine M; Massie, Allan B; Segev, Dorry L; Kilic, Ahmet; King, Elizabeth A; Bush, Errol L
INTRODUCTION/BACKGROUND:Transplants with hearts and lungs from donors with hepatitis C virus (HCV D+) have been proven safe and effective since development of direct-acting antivirals, yet the presence of HCV + persists as a reason to decline organs. METHODS:We identified adult candidates listed January 1, 2015-March 8, 2023 for heart or lung transplant using the Scientific Registry of Transplant Recipients. We identified individual-level and center-level characteristics associated with listing to consider HCV D+ offers using multilevel logistic regression in a multivariable framework. RESULTS:Over the study period, the annual percentage of candidates willing to consider HCV D+ offers increased for both heart (9.5%-74.3%) and lung (7.8%-59.5%), as did the percentage of centers listing candidates for HCV D+ heart (52.9%-91.1%) and lung (32.8%-82.8%) offers. Candidates at centers with more experience with HCV D+ transplants were more likely to consider HCV D+ organ offers. After adjustment, listing center explained 70% and 78% of the residual variance in willingness to consider HCV D+ hearts and lungs, respectively. CONCLUSIONS:Although listing for consideration of HCV D+ offers has increased, it varies by transplant center. Center-level barriers to consideration of HCV D+ organs reduce recipients' transplant access.
PMID: 39098116
ISSN: 1095-8673
CID: 5696692

OPTN/SRTR 2022 Annual Data Report: COVID-19

Miller, Jonathan M; Ahn, Yoon Son; Hart, Allyson; Segev, Dorry L; Schladt, David P; Livelli, Kathryn T; Lindblad, Kelsi A; Israni, Ajay K; Snyder, Jon J
This chapter updates the COVID-19 chapter from the 2021 Annual Data Report with trends through November 12, 2022, and introduces trends in recovery and use of organs from donors with a positive COVID-19 test. Posttransplant mortality and graft failure, which remained a concern in all organs at the last report due to the Omicron variant wave, have returned to lower levels in the most recent available data through November 2022. Use of organs from donors with a positive COVID-19 test has grown, particularly after the first year of the pandemic. Mortality due to COVID-19 should continue to be monitored, but most other measures have sustained their recovery and may now be responding more to changes in policy than to ongoing concerns with COVID-19.
PMID: 38431365
ISSN: 1600-6143
CID: 5691732