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

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.

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.

Evolving Trends in Kidney Transplant Outcomes Among Older Adults: A Comparative Analysis Before and During the COVID-19 Pandemic.

Background: Advancements in medical technology, healthcare delivery, and organ allocation resulted in improved patient/graft survival for older (age ≥65) kidney transplant (KT) recipients. However, the recent trends in these post-KT outcomes are uncertain in light of the mounting burden of cardiovascular disease, changing kidney allocation policies, heterogeneity in candidates' risk profile, and the coronavirus disease 2019 pandemic. Thus, we examined secular trends in post-KT outcomes among older and younger KT recipients over the last 3 decades. Methods: We identified 73 078 older and 378 800 younger adult (aged 18-64) recipients using Scientific Registry of Transplant Recipients (1990-2022). KTs were grouped into 6 prepandemic eras and 1 postpandemic-onset era. Kaplan-Meier and Cox proportional hazards models were used to examine temporal trends in post-KT mortality and death-censored graft failure. Results: From 1990 to 2022, a 19-fold increase in the proportion of older KT recipients was observed compared to a 2-fold increase in younger adults despite a slight decline in the absolute number of older recipients in 2020. The mortality risk for older recipients between 2015 and March 14, 2020, was 39% (adjusted hazard ratio [aHR] = 0.61, 95% confidence interval [CI], 0.50-0.75) lower compared to 1990-1994, whereas that for younger adults was 47% lower (aHR = 0.53, 95% CI, 0.48-0.59). However, mortality risk during the pandemic was 25% lower (aHR = 0.75, 95% CI, 0.61-0.93) in older adults and 37% lower in younger adults (aHR = 0.63, 95% CI, 0.56-0.70) relative to 1990-1994. For both populations, the risk of graft failure declined over time and was unaffected during the pandemic relative to the preceding period. Conclusions: The steady improvements in 5-y mortality and graft survival were disrupted during the pandemic, particularly among older adults. Specifically, mortality among older adults reflected rates seen 20 y prior.

Antibody Kinetics after Three Doses of SARS-CoV-2 mRNA Vaccination in Patients with Inflammatory Bowel Disease.

Background: The emergence of new SARS-CoV-2 variants calls for more data on SARS-CoV-2 mRNA vaccine response. Aims: We aimed to assess the response to a third mRNA vaccine dose against SARS-CoV-2 in inflammatory bowel disease (IBD) patients. Methods: This was a single-center, observational prospective study of IBD patients who received a third mRNA vaccine dose against SARS-CoV-2. Antibody titers were taken post-third-dose at one and three months using the Roche Elecsys anti-SARS-CoV-2-S enzyme immunoassay. Titers less than 0.8 units/mL were considered negative according to the manufactures. Titers between 0.8 units/mL and 250 units/mL were considered non-neutralizing. Titers greater than 250 units/mL were considered neutralizing. Results: Eighty-three patients were included, all of whom had detectable antibodies at 3 months post-third dose. A total of 89% showed neutralizing and 11% non-neutralizing titers. Participants with non-neutralizing titers were more likely to be on systemic corticosteroids (p = 0.04). Two participants seroconverted from negative to positive, whereas 86% with non-neutralizing titers boosted to neutralizing levels. Only one participant with neutralizing titers after a third dose had a decrease to a non-neutralizing level within 3 months. Conclusions: Our findings support the ongoing recommendations for additional doses in immunocompromised individuals. However, longitudinal studies with a greater-sized patient population are needed.

The unfinished journey toward transplant equity: an analysis of racial/ethnic disparities for children after the implementation of the Kidney Allocation System in 2014.

BACKGROUND: Disparities in pediatric kidney transplantation (KT) result in reduced access and worse outcomes for minority children. We assessed the impact of recent systems changes on these disparities. METHODS: This is a retrospective cohort study of pediatric patients utilizing data from the US Renal Data System (n = 7547) and Scientific Registry of Transplant Recipients (n = 6567 waitlisted and n = 6848 transplanted patients). We compared access to transplantation, time to deceased donor kidney transplant (DDKT), and allograft failure (ACGF) in the 5 years preceding implementation of the Kidney Allocation System (KAS) to the 5 years post-KAS implementation 2010-2014 vs. 2015-2019, respectively. RESULTS: Compared to the pre-KAS era, post-KAS candidates were more likely to be pre-emptively listed (26.8% vs. 38.1%, p < 0.001), pre-emptively transplanted (23.8% vs. 28.0%, p < 0.001), and less likely to have private insurance (35.6% vs. 32.3%, p = 0.01), but these were not uniform across racial groups. Compared to white children, Black and Hispanic children had a lower likelihood of transplant listing within 2 years of first dialysis service (aHR 0.590.670.76 and 0.730.820.92, respectively) in the post-KAS era. Time to DDKT was comparable across all racial groups in the post-KAS era. Compared to white children, Black DDKT recipients have more 5-year ACGF (aHR 1.001.432.06 p = 0.05) while there was no difference in 3- or 5-year ACGF among LDKT recipients. CONCLUSIONS: After KAS implementation, there is equity in time to DDKT. Pre-KAS increased hazard of ACGF among Black children has decreased in the post-KAS era; however, persistent disparities exist in time to transplant listing among Black and Hispanic children when compared to white children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Transplantation Amid a Pandemic: The Fall and Rise of Kidney Transplantation in the United States.

Following the outbreak of coronavirus disease 2019 (COVID-19) in the United States, the number of kidney waitlist additions and living-donor and deceased-donor kidney transplants (LDKT/DDKT) decreased substantially but began recovering within a few months. Since then, there have been several additional waves of infection, most notably, the Delta and Omicron surges beginning in August and December 2021, respectively. Methods: Using SRTR data, we compared observed waitlist registrations, waitlist mortality, waitlist removal due to deteriorating condition, LDKT, and DDKT over 5 distinct pandemic periods to expected events based on calculations from preepidemic data while accounting for seasonality and secular trends. Results: Although the number of daily waitlist additions has been increasing since May 2020, the size of the active waitlist has consistently declined, reaching a minimum of 52 556 on February 27, 2022. The recent Omicron surge knocked LDKT from 25% below baseline (incidence rate ratio [IRR] = 0.690.750.81) during the Delta wave to 38% below baseline (IRR = 0.580.620.67). DDKT, however, was less affected by the Omicron wave (IRR = 0.850.890.93 and 0.880.920.96 during the Delta and Omicron waves, respectively). Waitlist death decreased from 56% above baseline (IRR = 1.431.561.70) during Delta to 41% above baseline during Omicron, whereas waitlist removal due to deteriorating condition remained at baseline/expected levels during the Delta wave (IRR = 0.931.021.12) and the Omicron wave (IRR = 0.991.071.16). Conclusions: Despite exceptionally high COVID-19 incidence during the Omicron wave, the transplant system responded similarly to prior waves that imposed a lesser disease burden, demonstrating the transplant system's growing adaptations and resilience to this now endemic disease.

Trends in use and three-year outcomes of hepatitis C virus-viremic donor lung transplants for hepatitis C virus-seronegative recipients.

OBJECTIVE: The feasibility and 6-month outcome safety of lung transplants (LTs) from hepatitis C virus (HCV)-viremic donors for HCV-seronegative recipients (R-) were established in 2019, but longer-term safety and uptake of this practice nationally remain unknown. METHODS: We identified HCV-seronegative LT recipients (R-) 2015-2020 using the Scientific Registry of Transplant Recipients. We classified donors as seronegative (D-) or viremic (D+). We used χ2 testing, rank-sum testing, and Cox regression to compare posttransplant outcomes between HCV D+/R- and D-/R- LT recipients. RESULTS: HCV D+/R- LT increased from 2 to 97/year; centers performing HCV D+/R- LT increased from 1 to 25. HCV D+/R- versus HCV D-/R- LT recipients had more obstructive disease (35.7% vs 23.3%, P < .001), lower lung allocation score (36.5 vs 41.1, P < .001), and longer waitlist time (P = .002). HCV D+/R- LT had similar risk of acute rejection (adjusted odds ratio [aOR], 0.87; P = .58), extracorporeal membranous oxygenation (aOR, 1.94; P = .10), and tracheostomy (aOR, 0.42; P = .16); similar median hospital stay (P = .07); and lower risk of ventilator > 48 hours (aOR, 0.68; P = .006). Adjusting for donor, recipient, and transplant characteristics, risk of all-cause graft failure and mortality were similar at 30 days, 1 year, and 3 years for HCV D+/R- versus HCV D-/R- LT (all P > .1), as well as for high- (≥20/year) versus low-volume LT centers and high- (≥5/year) versus low-volume HCV D+/R- LT centers (all P > .5). CONCLUSIONS: HCV D+/R- and HCV D-/R- LT have similar outcomes at 3 years posttransplant. These results underscore the safety of HCV D+/R- LT and the potential benefit of expanding this practice further.

Patient and Graft Survival After A1/A2-incompatible Living Donor Kidney Transplantation.

ABO type B and O kidney transplant candidates have increased difficulty identifying a compatible donor for living donor kidney transplantation (LDKT) and are harder to match in kidney paired donation registries. A2-incompatible (A2i) LDKT increases access to LDKT for these patients. To better inform living donor selection, we evaluated the association between A2i LDKT and patient and graft survival. Methods: We used weighted Cox regression to compare mortality, death-censored graft failure, and all-cause graft loss in A2i versus ABO-compatible (ABOc) recipients. Results: Using Scientific Registry of Transplant Recipients data 2000-2019, we identified 345 A2i LDKT recipients. Mortality was comparable among A2i and ABOc recipients; weighted 1-/5-/10-y mortality was 0.9%/6.5%/24.2%, respectively, among A2i LDKT recipients versus 1.4%/7.7%/22.2%, respectively, among ABOc LDKT recipients (weighted hazard ratio [wHR], 0.811.041.33; P = 0.8). However, A2i recipients faced higher risk of death-censored graft failure; weighted 1-/5-/10-y graft failure was 5.7%/11.6%/22.4% for A2i versus 1.7%/7.5%/17.2% for ABOc recipients (wHR in year 1 = 2.243.565.66; through year 5 = 1.251.782.53; through year 10 = 1.151.552.07). By comparison, 1-/5-/10-y wHRs for A1-incompatible recipients were 0.631.966.08/0.390.942.27/0.390.831.74. Conclusions: A2i LDKT is generally safe, but A2i donor/recipient pairs should be counseled about the increased risk of graft failure and be monitored as closely as their A1-incompatible counterparts posttransplant.

Predicting a Positive Antibody Response After 2 SARS-CoV-2 mRNA Vaccines in Transplant Recipients: A Machine Learning Approach With External Validation.

BACKGROUND: Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations. METHODS: Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines. External validation of the model was performed using a cohort of 512 SOTRs at Houston Methodist Hospital. RESULTS: Mycophenolate mofetil use, a shorter time since transplant, and older age were the strongest predictors of a negative antibody response, collectively contributing to 76% of the model's prediction performance. Other clinical factors, including transplanted organ, vaccine type (mRNA-1273 versus BNT162b2), sex, race, and other immunosuppressants, showed comparatively weaker associations with an antibody response. This model showed moderate prediction performance, with an area under the receiver operating characteristic curve of 0.79 in our cohort and 0.67 in the external validation cohort. An online calculator based on our prediction model is available at http://transplantmodels.com/covidvaccine/ . CONCLUSIONS: Our machine learning model helps understand which transplant patients need closer follow-up and additional doses of vaccine to achieve protective immunity. The online calculator based on this model can be incorporated into transplant providers' practice to facilitate patient-centric, precision risk stratification and inform vaccination strategies among SOTRs.

The Landscape of Nondirected Living Liver Donation in the United States.

BACKGROUND: Living donor liver transplants (LDLTs) including those from nondirected donors (NDDs) have increased during the past decade, and center-level variations in LDLTs have not yet been described. We sought to quantify changes in the volume of NDD transplants over time and variation in NDD volume between transplant centers. We further examined characteristics of living liver donors and identified factors potentially associated with receiving an NDD liver transplant. METHODS: Using Scientific Registry of Transplant Recipients data between March 01, 2002, and December 31, 2020, we compared 173 NDDs with 5704 DLDs and 167 NDD recipients with 1153 waitlist candidates. RESULTS: NDDs increased from 1 (0.4% of LDLTs) in 2002 to 58 (12% of LDLTs) in 2020. Of 150 transplant centers, 35 performed at least 1 NDD transplant. Compared with waitlist candidates, adult NDD recipients were less frequently males (39% versus 62%, P < 0.001), had a lower model for end-stage liver disease (16 versus 18, P = 0.01), and spent fewer days on the waitlist (173 versus 246, P = 0.02). Compared with waitlist candidates, pediatric NDD recipients were younger (50% versus 12% age <2 y, P < 0.001) and more often diagnosed with biliary atresia (66% versus 41%, P < 0.001). Compared with DLDs, NDDs were older (40 versus 35 y, P < 0.001), college educated (83% versus 64%, P < 0.001), White (92% versus 78%, P < 0.001), and more frequently donated left-lateral segment grafts (32.0% versus 14%, P < 0.001). CONCLUSIONS: Liver NDD transplants continue to expand but remain concentrated at a few centers. Graft distribution favors female adults and pediatric patients with biliary atresia. Racial inequities in adult or pediatric center-level NDD graft distribution were not observed.

Examination of Racial and Socioeconomic Disparity in Use of Nondirected Kidney Donation in the US.

BACKGROUND: Nondirected donor (NDD) kidney transplant (NDDKT) continues to improve organ access for waitlisted candidates. Although NDDs are becoming increasingly common, there has been no contemporary evaluation of NDD allograft use, and it is vital to understand sociodemographic, as well as center-level, use across the US. STUDY DESIGN: Using national data from the Scientific Registry for Transplant Recipients, this study characterized NDDs, NDDKT recipients, and center-level distribution of NDDKT. Directed donor and NDD characteristics were compared using Fisher's exact and Wilcoxon rank-sum tests for categorical and continuous variables, respectively. Multivariable logistic regression was used to identify characteristics associated with receiving NDDKT, and center distribution of NDDKT was assessed using the Gini coefficient. RESULTS: NDDKT increased from 1.4% (n = 154) of all living donor kidney transplants in 2010 to 6.5% (n = 338) in 2020. Compared with directed living donors, NDDs were older (median [IQR], 44 [33 to 54] vs 43 [33 to 52], p < 0.01), more often male (40.2% vs 36.7%, p < 0.001), and White (91.4% vs 69.5%, p < 0.001). White adult candidates were more likely to receive NDDKT compared with Black (adjusted odds ratio [aOR], 0.300.340.39, p < 0.001), Hispanic/Latino (aOR, 0.360.420.48, p < 0.001), and Other (aOR, 0.410.470.55, p < 0.001) candidates. Black pediatric candidates had lower odds of receiving NDDKT (aOR, 0.090.220.54, p = 0.02). The proportion of centers performing NDDKT has increased from 2010 to 2020 (Gini = 0.77 vs 0.68). CONCLUSIONS: Although more centers are performing NDDKT, racial disparities persist among NDDs and NDDKT recipients. Continued effort is needed to recruit living kidney donors and improve access to living donation for minority groups in the US. (J Am Coll Surg 2022;234:000-00. © 2022 by the American College of Surgeons).

Trends and three-year outcomes of hepatitis C virus-viremic donor heart transplant for hepatitis C virus-seronegative recipients.

Objective: Heart transplants (HTs) from hepatitis C virus (HCV)-viremic donors to HCV-seronegative recipients (HCV D+/R-) have good 6-month outcomes, but practice uptake and long-term outcomes overall and among candidates on mechanical circulatory support (MCS) have yet to be established. Methods: Using the Scientific Registry of Transplant Recipients, we identified US adult HCV-seronegative HT recipients (R-) from 2015 to 2021. We classified donors as HCV-seronegative (D-) or HCV-viremic (D+). We used multivariable regression to compare post-HT extracorporeal membranous oxygenation, dialysis, pacemaker, acute rejection, and risk of post-HT mortality between HCV D+/R- and HCV D-/R-. Models were adjusted for donor, recipient, and transplant characteristics and center HT volume. We performed subgroup analyses of recipients bridged with MCS. Results: From 2015 to 2021, the number of HCV D+/R- HT increased from 1 to 181 and the number of centers performing HCV D+/R- HT increased from 1 to 60. Compared with HCV D-/R- recipients, HCV D+/R- versus D-/R- recipients overall and among patients bridged with MCS had similar odds of post-HT extracorporeal membranous oxygenation, dialysis, pacemaker, and acute rejection; and mortality risk at 30 days, 1 year, and 3 years (all P > .05). High center HT volume but not HCV D+/R- volume (<5 vs >5 in any year) was associated with lower mortality for HCV D+/R- HT. Conclusions: HCV D+/R- and D-/R- HT have similar outcomes at 3 years' posttransplant. These results underscore the opportunity provided by HCV D+/R- HT, including among the growing population bridged with MCS, and the potential benefit of further expanding use of HCV+ allografts.

Kidney Transplant Recipient Attitudes Toward a SARS-CoV-2 Vaccine.

A widely accepted severe acute respiratory syndrome 2 (SARS-CoV-2) vaccine could protect vulnerable populations, but the willingness of solid organ transplant recipients (SOTRs) to accept a potential vaccine remains unknown. METHODS: We conducted a national survey of 1308 SOTRs and 1617 non-SOTRs between November 11 and December 2, 2020 through the network of the National Kidney Foundation. RESULTS: Respondents were largely White (73.2%), female (61.1%), and college graduates (56.2%). Among SOTRs, half (49.5%) were unsure or would be unwilling to receive a SARS-CoV-2 vaccine once available. Major concerns included potential side effects (85.2%), lack of rigor in the testing and development process (69.7%), and fear of incompatibility with organ transplants (75.4%). Even after the announcement of the high efficacy of the mRNA-1273 vaccine (Moderna Inc.) at the time of survey distribution, likeliness to receive a vaccine only slightly increased (53.5% before announcement versus 57.8% after the announcement). However, 86.8% of SOTRs would accept a vaccine if recommended by a transplant provider. CONCLUSIONS: SOTRs reported skepticism in receiving a potential SARS-CoV-2 vaccine, even after announcements of high vaccine efficacy. Reassuringly, transplant providers may be the defining influence in vaccine acceptance and will likely have a critical role to play in promoting vaccine adherence.