Faculty Bibliography

BACKGROUND:Organ Procurement and Transplantation Network (OPTN) policy requires 2 years of follow-up for living kidney donors (LKDs); however, many transplant hospitals struggle to meet this requirement. We developed and tested a mobile health (mHealth) system for LKD follow-up in a pilot randomized-controlled trial (RCT). METHODS:LKDs were randomly assigned to either the intervention (mHealth + standard of care) or control arm (standard of care). We assessed OPTN policy-defined completeness and timeliness of 6-month, 1-year, and 2-year follow-ups. Four hundred LKDs were enrolled in the study (June 2018 to February 2021). RESULTS:At 6-month follow-up, a higher proportion of the intervention arm participants completed composite visits (97.5% vs. 91.5%, p = 0.01). Both arms had similar compliance rates at 1- and 2-year follow-up (92.0% vs. 89.5%, p = 0.49, and 66.5% vs. 65.0%, p = 0.83). Intervention arm participants completed 6-month follow-up 11 days earlier than their counterparts (p = 0.009). CONCLUSION/CONCLUSIONS:mHealth technologies improved 6-month follow-up, but did not impact 1- and 2-year LKD follow-up in this single-center RCT. Other strategies, such as providing services beyond data collection, may be necessary to improve donor engagement and support LDK's long-term follow-up.

INTRODUCTION/BACKGROUND:Predicting graft failure risk in pediatric liver transplantation (LT) recipients could identify areas for improving management. Persistent cognitive, motor, academic, and functional deficits are common in recipients and their impact on graft survival following LT helps inform risk prediction. METHODS:Using SRTR data 2008-2023, we evaluated the cognitive, motor, academic, and functional deficits of LT recipients at time of transplant to 14 years post-LT. We compared all cause graft failure (ACGF) among patients with versus without pre-LT and 1-year post-LT deficits using Cox regression, adjusting for recipient characteristics. We calculated an individual risk score for ACGF. RESULTS:In 8062 pediatric LT recipients median age 3 (IQR: 1, 10), 28.0%, 29.5%, 35.0%, and 79.8% of recipients had pre-LT deficits in cognition, motor, academic activity, and functional status respectively. This decreased to 23.0%, 18.1%, 14.2%, and 38.7% 1-year post-LT. Increased hazard of ACGF was noted in recipients with pre-LT decreased functional status (aHR = 1.13 (per 10% decrease), 95% CI: 1.10-1.15, p < 0.001), definite motor delay (aHR = 1.60, 95% CI: 1.21-2.10, p < 0.001), and inability to participate in academics (aHR = 1.49, 95% CI: 1.08-1.89, p = 0.01), but not delays in cognition (aHR = 0.91, 95% CI: 0.69-1.21, p = 0.19). Our risk score predicting ACGF demonstrated improved predictive performance compared to clinical parameters alone (C-statistic = 0.70 (0.67, 0.72) vs. 0.66 (0.64, 0.69), p < 0.001). CONCLUSIONS:Pediatric LT recipients with pre- or post-LT motor, academic, and functional deficits are at higher risk for ACGF. Care should be taken to assess deficits to identify patients who may benefit from functional intervention to potentially reduce ACGF risk.

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.

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.

BACKGROUND/UNASSIGNED:A potential long-term complication of living kidney donation in male donors is scrotal swelling on the same side as the nephrectomy, and some undergo surgery to relieve discomfort from the fluid collection. The long-term risk for this outcome attributable to donation is unknown. OBJECTIVE/UNASSIGNED:To evaluate long-term scrotal surgery rates after laparoscopic nephrectomy in male living kidney donors compared with nondonors. DESIGN/UNASSIGNED:Population-based cohort study (2002 to 2024). (ClinicalTrials.gov: NCT06716723). SETTING/UNASSIGNED:Linked administrative health care databases in Ontario, Canada. PARTICIPANTS/UNASSIGNED:898 male living kidney donors who had a laparoscopic nephrectomy were matched in a 1:10 ratio with 8980 male nondonors from the general population. The matching characteristics were age, date of cohort entry, rural residence, income, prior vasectomy, and prior inguinal hernia repair. Participants were followed for a median of 9 years, up to 22 years. MEASUREMENTS/UNASSIGNED:The primary outcome was hospitalization for surgery to address a unilateral scrotal fluid collection. RESULTS/UNASSIGNED:< 0.001). The median time from donation to scrotal surgery was 5.2 years (IQR, 3.3 to 8.4 years); more than 90% of the surgeries were hydrocelectomies and were performed under general anesthesia. Over 20 years, the cumulative incidence was 13.8% in donors versus 0.7% in nondonors. LIMITATION/UNASSIGNED:The precise causal mechanism remains unknown. CONCLUSION/UNASSIGNED:Laparoscopic nephrectomy is associated with a higher risk for subsequent scrotal surgery in male living kidney donors. PRIMARY FUNDING SOURCE/UNASSIGNED:Canadian Institutes of Health Research.

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.

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.