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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

Uptake and 1-year outcomes of lung transplantation for COVID-19

Ruck, Jessica M; Zhou, Alice L; Florissi, Isabella; Ha, Jinny S; Shah, Pali D; Massie, Allan B; Segev, Dorry L; Merlo, Christian A; Bush, Errol L
OBJECTIVE:End-stage lung disease from severe COVID-19 infection is an increasingly common indication for lung transplantation (LT), but there are limited data on outcomes. We evaluated 1-year COVID-19 LT outcomes. METHODS:We identified all adult US LT recipients January 2020 to October 2022 in the Scientific Registry for Transplant Recipients, using diagnosis codes to identify recipients transplanted for COVID-19. We used multivariable regression to compare in-hospital acute rejection, prolonged ventilator support, tracheostomy, dialysis, and 1-year mortality between COVID-19 and non-COVID-19 recipients, adjusting for donor, recipient, and transplant characteristics. RESULTS:LT for COVID-19 increased from 0.8% to 10.7% of total LT volume during 2020 to 2021. The number of centers performing LT for COVID-19 increased from 12 to 50. Recipients transplanted for COVID-19 were younger; were more likely to be male and Hispanic; were more likely to be on a ventilator, extracorporeal membrane oxygenation support, and dialysis pre-LT; were more likely to receive bilateral LT; and had higher lung allocation score and shorter waitlist time than other recipients (all P values < .001). COVID-19 LT had higher risk of prolonged ventilator support (adjusted odds ratio, 2.28; P < .001), tracheostomy (adjusted odds ratio 5.3; P < .001), and longer length of stay (median, 27 vs 19 days; P < .001). Risk of in-hospital acute rejection (adjusted odds ratio, 0.99; P = .95) and 1-year mortality (adjusted hazard ratio, 0.73; P = .12) were similar for COVID-19 LTs and LTs for other indications, even accounting for center-level differences. CONCLUSIONS:COVID-19 LT is associated with higher risk of immediate postoperative complications but similar risk of 1-year mortality despite more severe pre-LT illness. These encouraging results support the ongoing use of LT for COVID-19-related lung disease.
PMID: 37286074
ISSN: 1097-685x
CID: 5626312

COVID-19 and Access to Kidney Transplantation for Older Candidates in the United States: A National Registry Study

Menon, Gayathri; Li, Yiting; Musunuru, Amrusha; Zeiser, Laura B.; Massie, Allan B.; Segev, Dorry L.; McAdams-DeMarco, Mara A.
Rationale & Objective: Coronavirus disease (COVID)-19 has likely impacted accessibility to transplantation services among older adults (age ≥65 years). We quantified the impact of COVID-19 on kidney transplantation access for older kidney-only candidates registered on the United States (US) kidney waitlist. Study Design: Retrospective analysis of registry data. Setting & Participants: 57,222 older adults who were part of or added to the US kidney waitlist between January 1, 2016 and February 28, 2022, identified using the Scientific Registry of Transplant Recipients (SRTR). Exposures: Four COVID-19 waves and one nonwave period based on the national incidence of COVID-19 in the US (initial: March 15-May 30, 2020; winter 2020-2021: December 1, 2020-January 31, 2021; delta: August 1, 2021-September 30, 2021; omicron: December 1, 2021-February 28, 2022; nonwave: inter-wave periods). Outcomes: Waitlist registrations, deceased-donor kidney transplants, living-donor kidney transplants, waitlist mortality, and waitlist removals due to deteriorating condition (hereafter referred to as removals). Analytical Approach: Poisson regression for the adjusted incidence rate ratio (aIRR) of each outcome during the COVID-19 waves and the nonwave period relative to reference (January 1, 2016-December 31, 2019), adjusted for seasonality and secular trends. Results: Waitlist registrations initially declined and increased henceforth. Deceased-donor kidney transplants and living-donor kidney transplants remained below-expected levels during all waves. Waitlist mortality peaked during the winter 2020-2021 wave (aIRR: 1.701.982.30) and has declined since; mortality rates were 139%, 107%, and 251% above expected for Black candidates, men, and candidates aged ≥75 years, respectively, during the winter 2020-2021 wave. Removals increased from 22% below expected levels (initial wave) to 26% above expected levels (omicron wave); removals were nonsignificantly higher than expected during the omicron wave for older Black and Hispanic candidates. Limitations: The findings are not generalizable to those listed at earlier ages with prolonged waitlist times. Additionally, using national COVID-19 incidence does not consider local policy and health care variations. Lastly, aIRRs must be interpreted cautiously due to smaller daily event counts. Conclusions: COVID-19 was associated with fewer transplants and increased mortality and removals in older kidney transplant candidates. Transplant providers should consider this impact and implement policies and practices to ensure the continuity of care. Plain-Language Summary: The proportion of older adults on the kidney transplant waitlist is increasing, but the impact of COVID-19 on this population is not well characterized. In this study, we looked at incident waitlist registrations, deceased- and living-donor kidney transplants, and waitlist mortality and removals due to deteriorating condition over 4 waves of COVID-19. We found that transplantation services did not fully recover to prepandemic levels as of March 2022. Notably, racial/ethnic minorities and older men experienced lower rates of kidney transplants and higher rates of waitlist mortality, respectively, relative to White candidates and older women. Identifying vulnerable subpopulations affected by COVID-19 and its long-term impact is crucial for creating strategies to ensure the continuity of care in this population during public health emergencies.
ISSN: 2590-0595
CID: 5630412

Letter to the editor: Poor sensitivity of anti-nucleocapsid antibody in detecting prior COVID-19 in vaccinated solid organ transplant recipients [Letter]

Alejo, Jennifer L; Chang, Teresa Py; Frey, Sarah; Nair, Goutham A; Abedon, Aura T; Nauroz, Zeba; Karaba, Andrew H; Avery, Robin K; Tobian, Aaron A R; Clarke, William A; Garonzik-Wang, Jacqueline M; Segev, Dorry L; Massie, Allan B; Werbel, William A
PMID: 38289891
ISSN: 1399-0012
CID: 5627522

A2/A2B to B Deceased Donor Kidney Transplantation in the KAS Era

Bisen, Shivani S; Zeiser, Laura B; Getsin, Samantha N; Chiang, Po-Yu; Stewart, Darren E; Herrick-Reynolds, Kayleigh; Yu, Sile; Desai, Niraj M; Al Ammary, Fawaz; Jackson, Kyle R; Segev, Dorry L; Lonze, Bonnie E; Massie, Allan B
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 SRTR data from 12/2014-6/2022 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"). 1-/3-/5-year DDKT rates were 32.1%/61.4%/72.1% among A2-eligible candidates and 14.1%/29.9%/44.1% among A2-ineligible candidates, with the former experiencing a 133% higher rate of DDKT (Cox weighted HR = 2.192.332.47; p<0.001). 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=0.5). 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>0.9) or all-cause graft loss (wHR 0.820.961.12, p=0.6). Following its broader adoption since the implementation of KAS, 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.
PMID: 38142955
ISSN: 1600-6143
CID: 5623432

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

Transplant Candidate Outcomes After Declining a DCD Liver in the United States

Ishaque, Tanveen; Eagleson, Mackenzie A; Bowring, Mary G; Motter, Jennifer D; Yu, Sile; Luo, Xun; Kernodle, Amber B; Gentry, Sommer; Garonzik-Wang, Jacqueline M; King, Elizabeth A; Segev, Dorry L; Massie, Allan B
BACKGROUND:In the context of the organ shortage, donation after circulatory death (DCD) provides an opportunity to expand the donor pool. Although deceased-donor liver transplantation from DCD donors has expanded, DCD livers continue to be discarded at elevated rates; the use of DCD livers from older donors, or donors with comorbidities, is controversial. METHODS:Using US registry data from 2009 to 2020, we identified 1564 candidates on whose behalf a DCD liver offer was accepted ("acceptors") and 16 981 candidates on whose behalf the same DCD offers were declined ("decliners"). We characterized outcomes of decliners using a competing risk framework and estimated the survival benefit (adjusted hazard ratio [95% confidence interval]) of accepting DCD livers using Cox regression. RESULTS:Within 10 y of DCD offer decline, 50.9% of candidates died or were removed from the waitlist before transplantation with any type of allograft. DCD acceptors had lower mortality compared with decliners at 10 y postoffer (35.4% versus 48.9%, P < 0.001). After adjustment for candidate covariates, DCD offer acceptance was associated with a 46% reduction in mortality (0.54 [0.49-0.61]). Acceptors of older (age ≥50), obese (body mass index ≥30), hypertensive, nonlocal, diabetic, and increased risk DCD livers had 44% (0.56 [0.42-0.73]), 40% (0.60 [0.49-0.74]), 48% (0.52 [0.41-0.66]), 46% (0.54 [0.45-0.65]), 32% (0.68 [0.43-1.05]), and 45% (0.55 [0.42-0.72]) lower mortality risk compared with DCD decliners, respectively. CONCLUSIONS:DCD offer acceptance is associated with considerable long-term survival benefits for liver transplant candidates, even with older DCD donors or donors with comorbidities. Increased recovery and utilization of DCD livers should be encouraged.
PMID: 37726882
ISSN: 1534-6080
CID: 5611472

Evaluating Cost-Effectiveness in Using High-Kidney Donor Profile Index Organs

Ellison, Trevor A; Bae, Sunjae; Chow, Eric K H; Massie, Allan B; Kucirka, Lauren M; Van Arendonk, Kyle J; Segev, Dorry L
A more granular donor kidney grading scale, the kidney donor profile index (KDPI), has recently emerged in contradistinction to the standard criteria donor/expanded criteria donor framework. In this paper, we built a Markov decision process model to evaluate the survival, quality-adjusted life years (QALY), and cost advantages of using high-KDPI kidneys based on multiple KDPI strata over a 60-month time horizon as opposed to remaining on the waiting list waiting for a lower-KDPI kidney. Data for the model were gathered from the Scientific Registry of Transplant Recipients and the United States Renal Data System Medicare parts A, B, and D databases. Of the 129,024 phenotypes delineated in this model, 65% of them would experience a survival benefit, 81% would experience an increase in QALYs, 87% would see cost-savings, and 76% would experience cost-savings per QALY from accepting a high-KDPI kidney rather than remaining on the waiting list waiting for a kidney of lower-KDPI. Classification and regression tree analysis (CART) revealed the main drivers of increased survival in accepting high-KDPI kidneys were wait time ≥30 months, panel reactive antibody (PRA) <90, age ≥45 to 65, diagnosis leading to renal failure, and prior transplantation. The CART analysis showed the main drivers of increased QALYs in accepting high-kidneys were wait time ≥30 months, PRA <90, and age ≥55 to 65.
PMID: 37925233
ISSN: 1873-2623
CID: 5607262

Characterizing the risk of human leukocyte antigen-incompatible living donor kidney transplantation in older recipients

Long, Jane J; Motter, Jennifer D; Jackson, Kyle R; Chen, Jennifer; Orandi, Babak J; Montgomery, Robert A; Stegall, Mark D; Jordan, Stanley C; Benedetti, Enrico; Dunn, Ty B; Ratner, Lloyd E; Kapur, Sandip; Pelletier, Ronald P; Roberts, John P; Melcher, Marc L; Singh, Pooja; Sudan, Debra L; Posner, Marc P; El-Amm, Jose M; Shapiro, Ron; Cooper, Matthew; Verbesey, Jennifer E; Lipkowitz, George S; Rees, Michael A; Marsh, Christopher L; Sankari, Bashir R; Gerber, David A; Wellen, Jason R; Bozorgzadeh, Adel; Gaber, A Osama; Heher, Eliot C; Weng, Francis L; Djamali, Arjang; Helderman, J Harold; Concepcion, Beatrice P; Brayman, Kenneth L; Oberholzer, Jose; Kozlowski, Tomasz; Covarrubias, Karina; Massie, Allan B; McAdams-DeMarco, Mara A; Segev, Dorry L; Garonzik-Wang, Jacqueline M
Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.
PMID: 37748554
ISSN: 1600-6143
CID: 5590142

HIV-positive liver transplant does not alter the latent viral reservoir in recipients with ART-suppressed HIV

Benner, Sarah E; Zhu, Xianming; Hussain, Sarah; Florman, Sander; Eby, Yolanda; Fernandez, Reinaldo E; Ostrander, Darin; Rana, Meenakshi; Ottmann, Shane; Hand, Jonathan; Price, Jennifer C; Pereira, Marcus R; Wojciechowski, David; Simkins, Jacques; Stosor, Valentina; Mehta, Sapna A; Aslam, Saima; Malinis, Maricar; Haidar, Ghady; Massie, Allan; Smith, Melissa L; Odim, Jonah; Morsheimer, Megan; Quinn, Thomas C; Laird, Gregory M; Siliciano, Robert; Balagopal, Ashwin; Segev, Dorry L; Durand, Christine M; Redd, Andrew D; Tobian, Aaron A R
The latent viral reservoir(LVR) remains a major barrier to HIV-1 curative strategies. It is unknown whether receiving a liver transplant from a donor with HIV might lead to an increase in the LVR since the liver is a large lymphoid organ. We found no differences in intact provirus, defective provirus, or the ratio of intact to defective provirus between recipients with ART-supporesed HIV who received a liver from a donor with(n = 19) or without HIV(n = 10). All measures remained stable from baseline by one-year post transplant. These data demonstrate that the LVR is stable after liver transplantation in people living with HIV.
PMID: 37379584
ISSN: 1537-6613
CID: 5540322