Faculty Bibliography

INTRODUCTION/BACKGROUND:The United States Organ Procurement and Transplantation Network mandates collection of 6-month, 1-year, and 2-year post-donation follow-up data on living kidney donors (LKDs), but many centers struggle to meet these requirements. This study investigated whether providing a financial incentive (mailed gift card) could increase patient compliance with LKD follow-up. METHODS:A parallel, non-blinded, 1:1 superiority randomized control trial of LKDs was conducted at two centers from March 2017 to February 2021. The control arm received standard of care (SOC): instructions to complete the mandated LKD follow-up consisting of a health questionnaire and laboratory measurements at 6 months, 1 year, and 2 years post-donation. The intervention arm received SOC and was mailed a $25 gift card for each timely completed follow-up. Compliance rates were compared at each timepoint using Poisson regression. RESULTS:at 2 years). Similarly, no differences were observed in compliance with clinical follow-up, laboratory follow-up, or individual questions or lab values. CONCLUSION/CONCLUSIONS:Mailed gift cards did not improve patient compliance with LKD follow-up requirements; such interventions may be counterproductive among LKDs. Further research is needed to investigate and address barriers to completing LKD follow-up. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT03090646.

BACKGROUND/UNASSIGNED:; environmental injustice) by racial/ethnic segregation (social injustice) on dementia diagnosis in ESKD. METHODS/UNASSIGNED:concentrations (annualized and matched to older adults' residential ZIP code at dialysis initiation) and by segregation scores (Theil's H method). FINDINGS/UNASSIGNED:and segregation. INTERPRETATION/UNASSIGNED:experienced an increased risk of dementia; this risk was particularly pronounced among individuals in high segregation and predominantly minority neighborhoods. Environmental and social injustices likely drive racial and ethnic disparities in dementia for older adults with ESKD, underscoring the need for interventions and policies to mitigate these injustices. FUNDING/UNASSIGNED:National Institutes of Health.

OBJECTIVE:Given frailty and comorbidities that occur with both aging and end-stage kidney disease (ESKD), it is unclear if older patients with ESKD derive the improved survival and kidney transplant (KT) access associated with Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). METHODS:Using 2006-2021 USRDS data, we identified 876 patients with RYGB and 1508 patients with SG and compared 5-year mortality by age-group (18-29/30-39/40-49/50-59/60-69/≥ 70 years) to nonsurgical matched controls using 1:3 Mahalanobis distance matching, Kaplan-Meier, and Cox regression. We also compared age-stratified KT incidence between waitlisted patients and controls. RESULTS:) for patients with SG versus controls. CONCLUSIONS:RYGB in older patients with ESKD is associated with increased mortality and lower KT likelihood, whereas SG is associated with decreased mortality and higher KT likelihood compared to nonsurgical matched controls. Choice of bariatric surgery type may play a role in improving survival for older patients with ESKD.

Xenotransplantation of genetically-modified pig kidneys offers a solution to the scarcity of organs for end-stage renal disease patients.¹ We performed a 61-day alpha-Gal knock-out pig kidney and thymic autograft transplant into a nephrectomized brain-dead human using clinically approved immunosuppression, without CD40 blockade or additional genetic modification. Hemodynamic and electrolyte stability and dialysis independence were achieved. Post-operative day (POD) 10 biopsies revealed glomerular IgM and IgA deposition, activation of early complement components and mesangiolysis with stable renal function without proteinuria, a phenotype not seen in allotransplantation. On POD 33, an abrupt increase in serum creatinine was associated with antibody-mediated rejection and increased donor-specific IgG. Plasma exchange, C3/C3b inhibition and rabbit anti-thymocyte globulin (rATG), completely reversed xenograft rejection. Pre-existing donor-reactive T cell clones expanded progressively in the circulation post-transplant, acquired an effector transcriptional profile and were detected in the POD 33 rejecting xenograft prior to rATG treatment. This study provides the first long-term physiologic, immunologic, and infectious disease monitoring of a pig-to-human kidney xenotransplant and indicates that pre-existing xenoreactive T cells and induced antibodies to unknown epitope(s) present a major challenge, despite significant immunosuppression. It also demonstrates that a minimally gene-edited pig kidney can support long-term life-sustaining physiologic functions in a human.

We sought to understand the potential impacts of a rapidly evolving donor pool on the annual recalibration of the kidney donor profile index (KDPI). Using OPTN data, we examined the kidney donor risk index (KDRI) among deceased kidney donors recovered 2011-2024. We mimicked the OPTN's annual re-mapping process to measure the KDRI-to-KDPI calibration drift and used Cox regression to translate this drift into all-cause graft failure rate differences. The 50th/75th/95th KDRI percentile among recovered donors rose from 1.19/1.47/2.0 in 2011 to 1.40/1.77/2.36 in 2024. For donors with the same KDRI, the KDPI assigned in 2024 was as much as 13 points lower than the KDPI assigned in 2012. Holding other factors constant, the KDRI-KDPI calibration shift equated to 7 years of increased age (65 vs. 58) for KDPI 86% donors. Five-year graft failure risk was 9% higher (RR: _1.0871.093_1.097) for a kidney assigned a KDPI of 86% in 2024 versus 2012. Organ recovery practices have changed. The relationship between KDPI and organ quality has become a moving target, complicating shared decision-making and altering the meaning of allocation policy thresholds. Alternative solutions to annually remapping KDPI, such as establishing a fixed reference cohort or migrating away from KDPI, could be considered.

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.

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.

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.