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Impact of recipient age on mortality among Cytomegalovirus (CMV)-seronegative lung transplant recipients with CMV-seropositive donors

Belga, Sara; Hussain, Sarah; Avery, Robin K; Nauroz, Zeba; Durand, Christine M; King, Elizabeth A; Massie, Allan; Segev, Dorry L; Connor, Avonne E; Bush, Errol L; Levy, Robert D; Shah, Pali; Werbel, William A
BACKGROUND:Cytomegalovirus (CMV)-seronegative lung transplant recipients (LTRs) with seropositive donors (CMV D+/R-) have the highest mortality of all CMV serostatuses. Due to immunosenescence and other factors, we hypothesized CMV D+/R- status might disproportionately impact older LTRs. Thus, we investigated whether recipient age modified the relationship between donor CMV status and mortality among CMV-seronegative LTRs. METHODS:Adult, CMV-seronegative first-time lung-only recipients were identified through the Scientific Registry of Transplant Recipients between May 2005 and December 2019. We used adjusted multivariable Cox regression to assess the relationship of donor CMV status and death. Interaction between recipient age and donor CMV was assessed via likelihood ratio testing of nested Cox models and by the relative excess risk due to interaction (RERI) and attributable proportion (AP) of joint effects. RESULTS:We identified 11,136 CMV-seronegative LTRs. The median age was 59 years; 65.2% were male, with leading transplant indication of idiopathic pulmonary fibrosis (35.6%); and 60.8% were CMV D+/R-. In multivariable modeling, CMV D+/R- status was associated with 27% increased hazard of death (adjusted hazard ratio: 1.27, 95% confidence interval: 1.21-1.34) compared to CMV D-/R-. Recipient age ≥60 years significantly modified the relationship between donor CMV-seropositive status and mortality on the additive scale, including RERI 0.24 and AP 11.4% (p = 0.001), that is, the interaction increased hazard of death by 0.24 and explained 11.4% of mortality in older CMV D+ recipients. CONCLUSIONS:Among CMV-seronegative LTRs, donor CMV-seropositive status confers higher risk of posttransplant mortality, which is amplified in older recipients. Future studies should define optimal strategies for CMV prevention and management in older D+/R- LTRs.
PMID: 38061469
ISSN: 1557-3117
CID: 5591372

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act

Motter, Jennifer D; Hussain, Sarah; Brown, Diane M; Florman, Sander; Rana, Meenakshi M; Friedman-Moraco, Rachel; Gilbert, Alexander J; Stock, Peter; Mehta, Shikha; Mehta, Sapna A; Stosor, Valentina; Elias, Nahel; Pereira, Marcus R; Haidar, Ghady; Malinis, Maricar; Morris, Michele I; Hand, Jonathan; Aslam, Saima; Schaenman, Joanna M; Baddley, John; Small, Catherine B; Wojciechowski, David; Santos, Carlos A Q; Blumberg, Emily A; Odim, Jonah; Apewokin, Senu K; Giorgakis, Emmanouil; Bowring, Mary Grace; Werbel, William A; Desai, Niraj M; Tobian, Aaron A R; Segev, Dorry L; Massie, Allan B; Durand, Christine M; ,
BACKGROUND:Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D+), it is crucial to understand whether this has impacted transplant rates for this population. METHODS:Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D+ kidneys (HOPE) compared with 46 025 candidates not listed for D+ kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D+, false-positive [FP; donor with false-positive HIV testing], D- [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS:HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D+, 34% D-, 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D-, 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates (P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS:Listing for D+ kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.
PMID: 38012862
ISSN: 1534-6080
CID: 5617332

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

Florissi, Isabella; Chidi, Alexis P; Liu, Yi; Ruck, Jessica M; Mauney, Carrinton; McAdams-DeMarco, Mara; Merlo, Christian A; Shah, Pali; Stewart, Darren E; Segev, Dorry L; Bush, Errol L
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.
PMID: 37673311
ISSN: 1552-6259
CID: 5633682

Advance Care Planning and Palliative Care Consultation in Kidney Transplantation

Fisher, Marlena C; Chen, Xiaomeng; Crews, Deidra C; DeGroot, Lyndsay; Eneanya, Nwamaka D; Ghildayal, Nidhi; Gold, Marshall; Liu, Yi; Sanders, Justin J; Scherer, Jennifer S; Segev, Dorry L; McAdams-DeMarco, Mara A
RATIONALE & OBJECTIVE/OBJECTIVE:Because of the high risk of waitlist mortality and posttransplant complications, kidney transplant (KT) patients may benefit from advance care planning (ACP) and palliative care consultation (PCC). We quantified the prevalence and racial disparities in ACP and PCC among KT candidates and recipients. STUDY DESIGN/METHODS:Prospective cohort study. SETTING & PARTICIPANTS/METHODS:2,575 adult KT candidates and 1,233 adult recipients (2008-2020). EXPOSURE/METHODS:Race and ethnicity. OUTCOMES/RESULTS:All reports of ACP and PCC were abstracted from chart review. ACP was defined as patient self-report of an advance directive, presence of an advance directive in the medical record, or a documented goals-of-care conversation with a provider. PCC was defined as an ordered referral or a documented palliative care note in the medical record. ANALYTICAL APPROACH/METHODS:Racial/ethnic disparities in ACP/PCC were estimated using adjusted logistic regression. RESULTS:21.4% of KT candidates and 34.9% of recipients engaged in ACP. There were racial/ethnic disparities in ACP among KT candidates (White, 24.4%; Black, 19.1%; Hispanic, 15%; other race and ethnicity, 21.1%; P=0.008) and recipients (White, 39.5%; Black, 31.2%; Hispanic, 26.3%; other race and ethnicity, 26.6%; P=0.007). After adjustment, Black KT recipients had a 29% lower likelihood of engaging in ACP (OR, 0.71; 95% CI, 0.55-0.91) than White KT recipients. Among older (aged≥65 years) recipients, those who were Black had a lower likelihood of engaging in ACP, but there was no racial disparity among younger recipients (P=0.020 for interaction). 4.2% of KT candidates and 5.1% of KT recipients engaged in PCC; there were no racial disparities in PCC among KT candidates (White, 5.3%; Black, 3.6%; Hispanic, 2.5%; other race and ethnicity, 2.1%; P=0.13) or recipients (White, 5.5%; Black, 5.6%; Hispanic, 0.0%; other race and ethnicity, 1.3%; P = 0.21). LIMITATIONS/CONCLUSIONS:Generalizability may be limited to academic transplant centers. CONCLUSIONS:ACP is not common among KT patients, and minoritized transplant patients are least likely to engage in ACP; PCC is less common. Future efforts should aim to integrate ACP and PCC into the KT process. PLAIN-LANGUAGE SUMMARY/UNASSIGNED:Kidney transplant (KT) candidates and recipients are at elevated risk of morbidity and mortality. They may benefit from completing a document or conversation with their palliative care provider that outlines their future health care wishes, known as advance care planning (ACP), which is a component of palliative care consultation (PCC). We wanted to determine how many KT candidates and recipients have engaged in ACP or PCC and identify potential racial disparities. We found that 21.4% of candidates and 34.9% of recipients engaged in ACP. After adjustment, Black recipients had a 29% lower likelihood of engaging in ACP. We found that 4.2% of KT candidates and 5.1% of KT recipients engaged in PCC, with no racial disparities found in PCC.
PMID: 37734687
ISSN: 1523-6838
CID: 5620472

Anti-Obesity Pharmacotherapy to Facilitate Living Kidney Donation

Orandi, Babak J; Lofton, Holly; Montgomery, Robert A; Segev, Dorry L
Obesity is a chronic, relapsing disease that increases the risks of living kidney donation; at the same time, transplant centers have liberalized body mass index constraints for donors. With the increasing number of anti-obesity medications available, the treatment of obesity with anti-obesity medications may increase the pool of potential donors and enhance donor safety. Anti-obesity medications are intended for long-term use given the chronic nature of obesity. Cessation of treatment can be expected to lead to weight regain and increases the risk of comorbidity rebound/development. In addition, anti-obesity medications are meant to be used in conjunction with-rather than in replacement of-diet and physical activity optimization. Anti-obesity medication management includes selecting medications that may ameliorate any co-existing medical conditions, avoiding those that are contraindicated in such conditions, and being sensitive to any out-of-pocket expenses that may be incurred by the potential donor. A number of questions remain regarding who will and should shoulder the costs of long-term obesity treatment for donors. In addition, future studies are needed to quantify the degree of weight loss and duration of weight loss maintenance needed to normalize the risk of adverse kidney outcomes relative to comparable non-donors and lower weight donors.
PMID: 38072121
ISSN: 1600-6143
CID: 5589452

Omicron Infections in Vaccinated Pediatric Solid Organ Transplant Recipients

McAteer, John; Kalluri, Divya D; Abedon, Rivka R; Qin, Caroline X; Auerbach, Scott R; Charnaya, Olga; Danziger-Isakov, Lara A; Ebel, Noelle H; Feldman, Amy G; Hsu, Evelyn K; Mohammad, Saeed; Perito, Emily R; Thomas, Ashley M; Chiang, Teresa P Y; Garonzik-Wang, Jacqueline M; Segev, Dorry L; Werbel, William A; Mogul, Douglas B
PMID: 38035755
ISSN: 2048-7207
CID: 5616982

Using Photovoice to Explore the Lived Environment and Experience of Older Adults with Frailty on their Kidney Transplant Journey

Hladek, Melissa deCardi; Wilson, Deborah; Krasnansky, Katie; McDaniel, Kennedy; Shanbhag, Meera; McAdams-DeMarco, Mara; Crews, Deidra C; Brennan, Daniel C; Taylor, Janiece; Segev, Dorry; Walston, Jeremy; Xue, Qian-Li; Szanton, Sarah L
BACKGROUND:Older adults with frailty and kidney failure face higher waitlist mortality and are more likely to be listed as inactive on the kidney transplant (KT) wait list. Photovoice is a qualitative participatory research method where participants use photographs to represent their environment, needs and experiences. It offers unique insight into the lived environment and experience of patients and may offer direction in how to improve functional independence, symptom burden, and kidney transplant outcomes in adults with frailty. METHODS:This photovoice study was embedded within a larger intervention adaptation project. Participants with pre-frailty or frailty awaiting a KT or recently post-transplant took photos with Polaroid cameras and wrote short descriptions for 11 prompts. Each participant completed a semi-structured interview wherein their photos were discussed. The team coded and discussed photos and interviews to determine overarching themes and implications. Focus groups were used to triangulate visual data findings. RESULTS:Sixteen participants completed both the photovoice and interview. Participants were a mean age of 60.5 years, 31.2% female, 43.4% self-identifying as Black, and 69% were frail. Outcomes were categorized into seven themes: functional space, home safety, medication management, adaptive coping, life changing nature of dialysis, support and communication. Visual data clarified and sometimes changed the interpretations of the text alone. Especially within the themes of home safety and functional space, safety hazards not previously recognized in the literature, like dialysis fluid storage, were identified. CONCLUSIONS:Photovoice contextualizes the living conditions and experiences of adults with frailty on the kidney transplant journey and could be a useful tool in geriatric nephrology and transplant. Addressing issues of home storage, organization, and accessibility should be explored as potential intervention targets. Incorporating participant values and goals into care decisions and interventional design should be further explored.
PMID: 38379153
ISSN: 2641-7650
CID: 5634252

Neighborhood Segregation and Access to Live Donor Kidney Transplantation

Li, Yiting; Menon, Gayathri; Kim, Byoungjun; Bae, Sunjae; Quint, Evelien E; Clark-Cutaia, Maya N; Wu, Wenbo; Thompson, Valerie L; Crews, Deidra C; Purnell, Tanjala S; Thorpe, Roland J; Szanton, Sarah L; Segev, Dorry L; McAdams DeMarco, Mara A
IMPORTANCE/UNASSIGNED:Identifying the mechanisms of structural racism, such as racial and ethnic segregation, is a crucial first step in addressing the persistent disparities in access to live donor kidney transplantation (LDKT). OBJECTIVE/UNASSIGNED:To assess whether segregation at the candidate's residential neighborhood and transplant center neighborhood is associated with access to LDKT. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:In this cohort study spanning January 1995 to December 2021, participants included non-Hispanic Black or White adult candidates for first-time LDKT reported in the US national transplant registry. The median (IQR) follow-up time for each participant was 1.9 (0.6-3.0) years. MAIN OUTCOME AND MEASURES/UNASSIGNED:Segregation, measured using the Theil H method to calculate segregation tertiles in zip code tabulation areas based on the American Community Survey 5-year estimates, reflects the heterogeneity in neighborhood racial and ethnic composition. To quantify the likelihood of LDKT by neighborhood segregation, cause-specific hazard models were adjusted for individual-level and neighborhood-level factors and included an interaction between segregation tertiles and race. RESULTS/UNASSIGNED:Among 162 587 candidates for kidney transplant, the mean (SD) age was 51.6 (13.2) years, 65 141 (40.1%) were female, 80 023 (49.2%) were Black, and 82 564 (50.8%) were White. Among Black candidates, living in a high-segregation neighborhood was associated with 10% (adjusted hazard ratio [AHR], 0.90 [95% CI, 0.84-0.97]) lower access to LDKT relative to residence in low-segregation neighborhoods; no such association was observed among White candidates (P for interaction = .01). Both Black candidates (AHR, 0.94 [95% CI, 0.89-1.00]) and White candidates (AHR, 0.92 [95% CI, 0.88-0.97]) listed at transplant centers in high-segregation neighborhoods had lower access to LDKT relative to their counterparts listed at centers in low-segregation neighborhoods (P for interaction = .64). Within high-segregation transplant center neighborhoods, candidates listed at predominantly minority neighborhoods had 17% lower access to LDKT relative to candidates listed at predominantly White neighborhoods (AHR, 0.83 [95% CI, 0.75-0.92]). Black candidates residing in or listed at transplant centers in predominantly minority neighborhoods had significantly lower likelihood of LDKT relative to White candidates residing in or listed at transplant centers located in predominantly White neighborhoods (65% and 64%, respectively). CONCLUSIONS/UNASSIGNED:Segregated residential and transplant center neighborhoods likely serve as a mechanism of structural racism, contributing to persistent racial disparities in access to LDKT. To promote equitable access, studies should assess targeted interventions (eg, community outreach clinics) to improve support for potential candidates and donors and ultimately mitigate the effects of segregation.
PMCID:10877505
PMID: 38372985
ISSN: 2168-6114
CID: 5634032

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

Patel, Suhani S; Kim, Jacqueline I; Stewart, Darren E; Segev, Dorry L; Massie, Allan B
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 χ2 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 = 0.981.061.14, P = 0.14; liver = 0.850.921.01, P = 0.07; lung = 0.910.991.08, P = 0.83; heart = 0.890.971.05, 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 = 0.770.840.91, P < 0.001; liver = 0.770.840.92, P < 0.001; lung = 0.740.810.90, P < 0.001; heart = 0.610.670.73, 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.
PMID: 38361232
ISSN: 1534-6080
CID: 5635942

The decedent model: A new paradigm for de-risking high stakes clinical trials like xenotransplantation

Montgomery, Robert A; Griesemer, Adam D; Segev, Dorry L; Sommer, Philip
The first 2 living recipients of pig hearts died unexpectedly within 2 months, despite both recipients receiving what over 30 years of nonhuman primate (NHP) research would suggest were the optimal gene edits and immunosuppression to ensure success. These results prompt us to question how faithfully data from the NHP model translate into human outcomes. Before attempting any further heart xenotransplants in living humans, it is highly advisable to gain a more comprehensive understanding of why the promising preclinical NHP data did not accurately predict outcomes in humans. It is also unlikely that additional NHP data will provide more information that would de-risk a xenoheart clinical trial because these cases were based on the best practices from the most successful NHP results to date. Although imperfect, the decedent model offers a complementary avenue to determine appropriate treatment regimens to control the human immune response to xenografts and better understand the biologic differences between humans and NHP that could lead to such starkly contrasting outcomes. Herein, we explore the potential benefits and drawbacks of the decedent model and contrast it to the advantages and disadvantages of the extensive body of data generated in the NHP xenoheart transplantation model.
PMID: 38341026
ISSN: 1600-6143
CID: 5635522