Faculty Bibliography

BACKGROUND:Frail kidney transplant (KT) candidates, characterized by low physical activity/function, have decreased chances of listing and increased risk of waitlist mortality. Impairments in these physical domains contribute to perceived physical burden and may exacerbate one another. Further, understanding the association of each domain individually with adverse outcomes may improve pre-KT risk stratification. METHODS:We leveraged 2708 KT candidates (age ≥ 18) from a two-center prospective cohort study (2014-2024). We assessed physical activity (Minnesota Leisure Time Physical Activity Questionnaire), physical function (gait speed), and physical burden (10 questions from the Kidney Disease Quality of Life Short Form) at evaluation. We quantified the association of these three physical domains with listing (Cox proportional hazards) and waitlist mortality (competing risks, Harrell's C-statistic). RESULTS:Among 2708 candidates, 40% had low physical activity, 16% had low physical function, and 54% had high physical burden. Candidates with impairment in these three physical domains were less likely to be listed (activity: adjusted hazard ratio [aHR] = 0.86, 95% confidence interval [CI]: 0.75-0.99; function: aHR = 0.54, 95%CI: 0.45-0.64; burden: aHR = 0.75, 95%CI: 0.67-0.83) and had a higher risk of waitlist mortality (activity: adjusted sub-hazard ratio [aSHR] = 1.51, 95%CI: 1.11-2.04; function: aSHR = 1.83, 95%CI: 1.30-2.58; burden: aSHR = 1.40, 95%CI: 1.09-1.82). Physical burden showed the best discrimination in predicting mortality after adjustment (Harrell's C-statistic = 0.6899). CONCLUSION/CONCLUSIONS:Although impairment in physical activity, function, and burden was all associated with KT listing and waitlist mortality, physical burden was the strongest predictor of waitlist mortality. KT centers should consider measuring physical burden - a simple, low-cost tool to help identify high-risk candidates for prehabilitation.

Given the unique risk profile of kidney transplant recipients (KTRs), characterizing their cardiovascular disease (CVD) risk after COVID-19 remains critical for targeted management. We performed a retrospective analysis of 809 clinically diagnosed symptomatic COVID-19 events among 778 KTRs from one Maryland health system (3/2020-1/2024) to characterize incidence and risk factors of post-COVID-19 CVD. We followed KTRs until composite CVD (acute coronary syndrome (ACS), stroke, heart failure (HF), CVD death), non-CVD death, or one year after COVID-19 and identified risk factors using LASSO-based sub-distribution hazards regression. Incidence of post-COVID CVD was 8.7% at one-year (2.7% ACS, 1.4% stroke, 3.6% HF, and 1.0% CVD death). KTRs with CVD history had higher incidence than those without (19.1% vs 5.0%). Older age, Black race, Hispanic ethnicity, prior CVD, and COVID-19 hospitalization increased post-COVID CVD risk; BMI>30 and treatment with remdesivir decreased post-COVID CVD risk. COVID-19 hospitalization conferred equivalent risk to prior CVD: incidence was 11.2% among KTRs with prior CVD but no hospitalization, 12.0% among KTRs with hospitalization but no prior CVD, 25.2% among KTRs with both, and 1.8% among KTRs with neither. Post-COVID-19 CVD risk was high among KTRs and hospitalization for COVID-19 was as important as having had a prior cardiovascular event.

BACKGROUND:on dementia may be more severe in this population. METHODS:and dementia risk factors using a Wald test. Models were adjusted for confounders, including social determinants of health. RESULTS:was associated with 1.90-fold higher odds of global cognitive impairment (95% CI: 1.48-2.46), and 3.29-fold higher risk of dementia (95% CI: 1.14-9.55). CONCLUSION/CONCLUSIONS:neighborhoods should discuss cognitive assessments and ways to increase physical activity with providers.

Older (aged ≥55 years) kidney transplant (KT) recipients diagnosed with a sleep disorder after transplantation may be at increased risk for developing dementia. Using the United States Renal Data System/Medicare claims (2010-2020), we identified 16 573 older KT recipients with a functioning graft 1-year post-KT. First-time sleep disorders and newly prescribed sleep medications were ascertained within the first year post-KT. We used cause-specific hazard models to estimate the adjusted hazard ratio of diagnosed dementia with inverse probability of treatment weights. Overall, 3615 (21.8%) KT recipients were newly diagnosed with sleep disorders. Recipients diagnosed with a sleep disorder had a 1.32-fold increased risk for dementia (95% CI:1.15-1.51); those with insomnia had a 1.56-fold increased risk (95% CI:1.20-2.03). Of those diagnosed with insomnia, only 7.5% underwent cognitive behavioral therapy for insomnia. Of the recipients, 12.9% with a sleep disorder were prescribed sleep medications. Recipients prescribed sleep medication had a 1.44-fold increased risk for dementia (95% CI:1.16-1.77). Those prescribed zolpidem, the most commonly prescribed medication (80.1%), had a 1.41-fold increased risk (95% CI:1.12-1.78) for dementia; those prescribed other sleep medications had 3.13-fold (95% CI:1.41-6.98) increased risk for dementia. Post-KT sleep disorders are modifiable dementia risk factors; medication-associated dementia risk should be weighed against other therapies such as cognitive behavioral therapy for insomnia during management.

Procurement biopsies are routinely obtained in the United States to evaluate kidneys considered for transplantation, but some argue that they may contribute to kidney nonutilization. Historically, biopsy decisions have been left solely to the discretion of organ procurement organizations (OPOs) and transplant centers. In September 2022, an organ procurement and transplantation network (OPTN) policy designating donors meeting specific clinical criteria as "biopsy-required" went into effect. Using OPTN data from 1 year before and after policy implementation, we used causal inference methods to estimate the policy's impacts on biopsy practices and kidney utilization. The overall biopsy rate remained stable at 62%, rising from 90.6% to 95.8% (P < .001) among biopsy-required kidneys while falling from 49.1% to 43.4% (P < .001) among biopsy-optional kidneys. After adjusting for changing donor characteristics, the policy was associated with a 5% decline in the biopsy rate (adjusted risk ratio = 0.95; P = .007). The overall kidney nonuse rate rose from 27.2% to 28.7%. After accounting for changes in donor characteristics, the policy was not associated with elevated nonuse (adjusted risk ratio = 0.96, P = .06). Although most OPOs are now biopsying nearly all required kidneys, practices still vary widely regarding biopsy-optional kidneys. No correlation was found between OPO-level changes in adjusted biopsy and nonuse rates (ρ = 0.05, P = .70). The OPTN policy has partially standardized biopsy practices without harming kidney utilization.

BACKGROUND:The HIV (human immunodeficiency virus) Organ Policy Equity (HOPE) Act legalized transplantation from both living and deceased donors with HIV to recipients with HIV (HIV D+/R+). Since its enactment, only a few living organ donations from people with HIV (PWH) have occurred compared to more deceased donations. The study aims to understand the perspectives of infectious disease providers and their awareness of HIV-positive donors with a reactive status (HIV D+/R+) to inform the practice, as kidney and liver transplants from these donors can now be conducted outside of research protocols. METHODS:Semi-structured interviews were conducted with infectious disease providers (n = 18) from October 2023 to March 2024 to assess their perceptions and knowledge of HIV D+/R+ living organ donation. Inductive thematic analysis was conducted to identify major themes. RESULTS:Most providers had a positive view of HIV D+/R+ living donation, noting its potential to expand the donor pool, reduce wait times, and reduce stigma surrounding organ transplantation for PWH. However, they expressed concerns about the long-term outcomes of donors and emphasized the importance of thorough evaluations, including assessments of the disease stage and comorbidities. Additionally, providers mentioned that they had limited knowledge of the HIV D+/R+ donation process and highlighted the need for educational resources and establishing formal relationships with transplant programs. CONCLUSIONS:The study findings highlight the need for evidence-based information resources for healthcare providers on HIV D+/R+ living donations.

BACKGROUND:Under the HOPE Act, transplants from donors with HIV to recipients with HIV (HIV D+/R+) have been largely limited to kidney and liver. However, recent modifications to HOPE research guidelines allow broader participation of cardiothoracic programs. METHODS:To quantify potential cardiothoracic HOPE donors, we used SRTR data (3/2016-12/2024) to identify 101,200 donors without HIV and 273 HOPE donors (with true and false positive HIV tests). Using logistic regression, we predicted the probability of having a heart or lung(s) used for transplant among donors without HIV that had a kidney or liver used. We then applied model parameters to HOPE donors that had a kidney or liver used to estimate the number of HOPE donors that might have been cardiothoracic donors if the practice were expanded. RESULTS:Among donors without HIV, cardiothoracic donation was associated with age, cause of death, hepatitis C, hypertension, diabetes, smoking, cardiovascular disease, blood gas, and circulatory death. Applying our model, an estimated 41.0% (N=111), 18.7% (N=51), and 15.2% (N=41) of HOPE donors were potential heart, any lung (single or double), or double-lung donors, as compared to 32.3%, 21.8%, and 18.2% of abdominal organ donors without HIV, respectively. This translated to an annual 13-18 potential heart and 5-8 potential lung transplants (of which 4-6 would be double-lung transplants) from HOPE donors. CONCLUSIONS:If HIV D+/R+ is more widely expanded to cardiothoracic transplantation, 41% of HOPE kidney and liver donors have potential to donate a heart and almost 20% to donate a lung to candidates with HIV.

BACKGROUND:Sarcopenia and myosteatosis are indicators of abnormal body composition (BC). Computed tomography (CT) imaging has proven to be an accurate modality for BC quantification in kidney transplantation (KT). We tested whether pre-KT CT-based BC was associated with both all-cause graft loss (ACGL) and mortality among adult recipients from two centers (Johns Hopkins Hospital [JHH] and University Medical Center Groningen [UMCG]). METHODS:Patients who underwent a KT between 2003 and 2020 were followed for a median (interquartile range) follow-up of 6.4 (4.6-8.5) years at JHH and 6.3 (5.1-7.5) years at UMCG. Cox proportional hazard models were used to estimate the associations of BC with ACGL/ mortality. Fine and Gray regression analysis was performed to assess the association between BC and death-censored graft loss. Prior to KT, 49% of recipients had sarcopenia and 66% had myosteatosis. RESULTS:In total 608 patients were included from JHH (N= 294) and UMCG (N=314). Sarcopenia was not associated with post-KT outcomes. Myosteatosis was associated with a higher risk of ACGL (adjusted hazard ratio 1.78, 95%CI:1.08 - 2.93) and mortality (adjusted hazard ratio 2.35, 95%CI: 1.27 - 4.33) at JHH, but showed no significant association at UMCG after adjusting for confounders. Myosteatosis did not show a significant association with death-censored graft loss at both centers. CONCLUSION/CONCLUSIONS:Myosteatosis ascertained from existing CT scans could help identify recipients at higher risk for ACGL who may benefit most from prehabilitation.