Faculty Bibliography

BACKGROUND:Brazil has a large public transplant program, but it remains unclear if the kidney waitlist criteria effectively allocate organs. This study aimed to investigate whether gender, ethnicity, clinical characteristics, and Brazilian regions affect the chance of deceased donor kidney transplant (DDKT). METHODS:We conducted a retrospective cohort study using the National Transplant System/Brazil database, which included all patients on the kidney transplant waitlist from January 2012 to December 2022, followed until May 2023. The primary outcome assessed was the chance of DDKT, measured using subdistribution hazard and cause-specific hazard models (subdistribution hazard ratio [sHR]). RESULTS:We analyzed 118 617 waitlisted patients over a 10-year study period. Male patients had an sHR of 1.07 ([95% CI: 1.05-1.10], p < 0.001), indicating a higher chance of DDTK. Patients of mixed race and Yellow/Indigenous ethnicity had lower rates of receiving a transplant compared to Caucasian patients, with sHR of 0.97 (95% CI: 0.95-1) and 0.89 (95% CI: 0.95-1), respectively. Patients from the South region had the highest chance of DDKT, followed by those from the Midwest and Northeast, compared to patients from the Southeast, with sHR of 2.53 (95% CI: 2.47-2.61), 1.21 (95% CI: 1.16-1.27), and 1.10 (95% CI: 1.07-1.13), respectively. The North region had the lowest chance of DDTK, sHR of 0.29 (95% CI: 0.27-0.31). CONCLUSION/CONCLUSIONS:We found that women and racial minorities faced disadvantages in kidney transplantation. Additionally, we observed regional disparities, with the North region having the lowest chance of DDKT and longer times on dialysis before being waitlisted. In contrast, patients in the South regions had a chance of DDKT and shorter times on dialysis before being waitlisted. It is urgent to implement approaches to enhance transplant capacity in the North region and address race and gender disparities in transplantation.

BACKGROUND:The prevalence and outcomes of COVID-19-associated invasive fungal infections (CAIFIs) in solid organ transplant recipients (SOTRs) remain poorly understood. METHODS:A retrospective cohort study of SOTRs with COVID-19 admitted to 5 hospitals within Johns Hopkins Medicine was performed between March 2020 and March 2022. Cox regression multilevel mixed-effects ordinal logistic regression was used. RESULTS:In the cohort of 276 SOTRs, 22 (8%) developed IFIs. The prevalence of CAIFIs was highest in lung transplant recipients (20%), followed by recipients of heart (2/28; 7.1%), liver (3/46; 6.5%), and kidney (7/149; 4.7%) transplants. In the overall cohort, only 42 of 276 SOTRs (15.2%) required mechanical ventilation; these included 11 of 22 SOTRs (50%) of the CAIFI group and 31 of 254 SOTRs (12.2%) of the no-CAIFI group. Compared with those without IFIs, SOTs with IFIs had worse outcomes and required more advanced life support (high-flow oxygen, vasopressor, and dialysis). SOTRs with CAIFIs had higher 1-y death-censored allograft failure (hazard ratio 1.6 5.1 16.4 , P  = 0.006) and 1-y mortality adjusting for oxygen requirement (adjusted hazard ratio 1.1 2.4 5.1 , P  < 0.001), compared with SOTRs without CAIFIs. CONCLUSIONS:The prevalence of CAIFIs in inpatient SOTRs with COVID-19 is substantial. Clinicians should be alert to the possibility of CAIFIs in SOTRs with COVID-19, particularly those requiring supplemental oxygen, regardless of their intubation status.

INTRODUCTION:Thoracoabdominal normothermic regional perfusion (TA-NRP) following cardiac death is an emerging multivisceral organ procurement technique. Recent national studies on outcomes of presumptive TA-NRP-procured organs are limited by potential misclassification since TA-NRP is not differentiated from donation after cardiac death (DCD) in registry data. METHODS:We studied 22 donors whose designees consented to TA-NRP and organ procurement performed at our institution between January 20, 2020 and July 3, 2022. We identified these donors in SRTR to describe organ utilization and recipient outcomes and compared them to recipients of traditional DCD (tDCD) and donation after brain death (DBD) organs during the same timeframe. RESULTS:All 22 donors progressed to cardiac arrest and underwent TA-NRP followed by heart, lung, kidney, and/or liver procurement. Median donor age was 41 years, 55% had anoxic brain injury, 45% were hypertensive, 0% were diabetic, and median kidney donor profile index was 40%. TA-NRP utilization was high across all organ types (88%-100%), with a higher percentage of kidneys procured via TA-NRP compared to tDCD (88% vs. 72%, p = .02). Recipient and graft survival ranged from 89% to 100% and were comparable to tDCD and DBD recipients (p ≥ .2). Delayed graft function was lower for kidneys procured from TA-NRP compared to tDCD donors (27% vs. 44%, p = .045). CONCLUSION:Procurement from TA-NRP donors yielded high organ utilization, with outcomes comparable to tDCD and DBD recipients across organ types. Further large-scale study of TA-NRP donors, facilitated by its capture in the national registry, will be critical to fully understand its impact as an organ procurement technique.

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.

BACKGROUND:Medical distrust may hinder kidney transplantation (KT) access. Among KT candidates evaluated for waitlisting, we identified factors associated with high distrust levels and quantified their association with waitlisting. METHODS:Among 812 candidates (2018-2023), we assessed distrust using the Revised Health Care System Distrust Scale across composite, competence, and values subscales. We used linear regression to quantify the associations between candidate and neighborhood-level factors and distrust scores. We used Cox models to quantify the associations between distrust scores and waitlisting. RESULTS:At KT evaluation, candidates who were aged 35-49 years (difference = 1.97, 95% CI: 0.78-3.16), female (difference = 1.10, 95% CI: 0.23-1.97), and Black (difference = 1.47, 95% CI: 0.47-2.47) were more likely to report higher composite distrust score. For subscales, candidates aged 35-49 were more likely to have higher competence distrust score (difference = 1.14, 95% CI: 0.59-1.68) and values distrust score (difference = 0.83, 95% CI: 0.05-1.61). Race/ethnicity (Black, difference = 1.42, 95% CI: 0.76-2.07; Hispanic, difference = 1.52, 95% CI: 0.35-2.69) was only associated with higher values distrust scores. Female candidates reporting higher rescaled values distrust scores (each one point) had a lower chance of waitlisting (aHR = 0.78, 95% CI: 0.63-0.98), whereas this association was not observed among males. Similarly, among non-White candidates, each 1-point increase in both rescaled composite (aHR = 0.87, 95% CI: 0.77-0.99) and values (aHR = 0.82, 95% CI: 0.68-0.99) distrust scores was associated with a lower chance of waitlisting, while there was no association among White candidates. CONCLUSION/CONCLUSIONS:Female, younger, and non-White candidates reported higher distrust scores. Values distrust may contribute to the long-standing racial/ethnic and gender disparities in access to KT. Implementing tailored strategies to reduce distrust in transplant care may improve KT access for groups that experience persistent disparities.

KEY POINTS:Regardless of race and ethnicity, older adults with kidney failure residing in or receiving care at dialysis facilities located in high-segregation neighborhoods were at a 1.63-fold and 1.53-fold higher risk of dementia diagnosis, respectively. Older adults with kidney failure residing in minority-predominant high-segregation neighborhoods had a 2.19-fold higher risk of dementia diagnosis compared with White individuals in White-predominant neighborhoods. BACKGROUND:a form of structural racism recently identified as a mechanism in numerous other health disparities. METHODS:We identified 901,065 older adults (aged ≥55 years) with kidney failure from 2003 to 2019 using the United States Renal Data System. We quantified dementia risk across tertiles of residential neighborhood segregation score using cause-specific hazard models, adjusting for individual- and neighborhood-level factors. We included an interaction term to quantify the differential effect of segregation on dementia diagnosis by race and ethnicity. RESULTS: CONCLUSIONS:Residing in or receiving care at dialysis facilities located in high-segregation neighborhoods was associated with a higher risk of dementia diagnosis among older individuals with kidney failure, particularly minoritized individuals.

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.

BACKGROUND:The number of living kidney donors in the United States has declined since 2005, with variations based on the donor-recipient relationship. The reasons for this decline are unclear, and strategies to mitigate declined donations remain elusive. We examined the change in donor number monthly (within-year) versus annually (between-years) to inform potentially modifiable factors for future interventions. METHODS:In this registry-based cohort analysis of 141 759 living kidney donors between 1995 and 2019, we used linear mixed-effects models for donor number per month and year to analyze between-year and within-year variation in donation. We used Poisson regression to quantify the change in the number of donors per season before and after 2005, stratified by donor-recipient relationship and zip-code household income tertile. RESULTS:We observed a consistent summer surge in donations during June, July, and August. This surge was statistically significant for related donors (incidence rate ratio [IRR] range: 1.12-1.33) and unrelated donors (IRR range: 1.06-1.16) across donor income tertiles. CONCLUSION/CONCLUSIONS:Our findings indicate lower rates of living kidney donation in non-summer months across income tertiles. Interventions are needed to address barriers to donation in non-summer seasons and facilitate donations throughout the year. Since the Organ Donor Leave Law provides a solid foundation for supporting year-round donation, extending the law's provisions beyond federal employees may mitigate identified seasonal barriers.

OBJECTIVE:Incidence and manifestations of postacute sequelae of coronavirus disease 2019 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases. METHODS:Persons aged ≥ 18 years with systemic autoimmune diseases were recruited into a national, prospective observational cohort of SARS-CoV-2 vaccination and infection between December 2020 and April 2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QOL) effect; PASC was defined as ≥ 1 symptom persisting for > 12 weeks. PASC syndromes were mapped by overlapping symptom domains. Characteristics were compared between participants who did vs did not report PASC. RESULTS:= 0.004). CONCLUSION/CONCLUSIONS:In a large, real-world cohort, 29.8% of persons with systemic autoimmune disease reported PASC, often affecting QOL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections.

OBJECTIVES/OBJECTIVE:Obesogenic medications are a putative contributor to the obesity epidemic. While 20% of adults take ≥1 obesogenic medication, the proportion in the end-stage kidney disease (ESKD) population-a group enriched for cardiometabolic complications-is unknown. Obesogenic medications may contribute to obesity and hamper weight loss efforts to achieve transplant listing. METHODS:Using 2017-2020 USRDS and Medicare claims, patients were identified as taking obesogenic medications if prescribed anticonvulsants, antidepressants, antidiabetics, anti-inflammatories, antipsychotics, and/or antihypertensives known to cause weight gain for ≥30 days in their first hemodialysis year. Ordinal logistic and Cox regression with inverse probability of treatment weighting were used to quantify obesogenic medications' association with body mass index (BMI) and listing, respectively. RESULTS:Among 271 401 hemodialysis initiates, 63.5% took ≥1 obesogenic medication. For those in underweight, normal weight, overweight, and class I, II, and III categories, 54.3%, 58.4%, 63.1%, 66.5%, 68.6%, and 68.8% took ≥1, respectively. Number of obesogenic medications was associated with increased BMI; use of one was associated with 13% increased odds of higher BMI (aOR [adjusted odds ratio] 1.14; 95%CI: 1.13-1.16; p < 0.001), use of three was associated with a 55% increase (aOR 1.55; 95%CI: 1.53-1.57; p < 0.001). Any use was associated with 6% lower odds of transplant listing (aHR [adjusted hazard ratio] 0.94; 95%CI: 0.92-0.96; p < 0.001). Within each BMI category, obesogenic medication use was associated with lower listing likelihood. CONCLUSIONS:Obesogenic medication use is common in ESKD patients-particularly those with obesity-and is associated with lower listing likelihood. Whenever possible, non-obesogenic alternatives should be chosen for ESKD patients attempting weight loss to achieve transplant listing.