Faculty Bibliography

With U.S. Food and Drug Administration (FDA) clearance of clinical trials of kidney xenotransplantation (XTx) in living humans, understanding the recipient experience is critical. Semi-structured interviews with the three living XTx recipients identified core domains of the recipient experience, including quality of life (QoL), fears about XTx, and healthcare team communication and support. Transcribed interviews were analyzed by two qualitative researchers using an inductive thematic approach and were mapped onto the Warwick Patient Experience Model, a validated framework to assess key aspects of patient satisfaction with the healthcare experience. All three recipients (53-year-old female; 66-year-old male; 54-year old male) described a restoration of hope, contrasted with their poor quality of life on dialysis. They emphasized that access to XTx and graft survival requires mutual confidence and commitment between recipients and healthcare teams. XTx recipients use dialysis as a point of reference when describing changes in their post-transplant QoL and seemed well-situated to handle the possibility of graft failure. These insights may aid in the creation of decision aids and educational materials tailored to the specific needs of XTx recipients.

BACKGROUND/UNASSIGNED:Understanding center-level decision-making for suboptimal kidney (SOK) offers is critical to ensure utilization of all transplantable kidneys. METHODS/UNASSIGNED:We quantified center-level variation in accepting SOK deceased donor kidney transplant (DDKT) offers using 2021-2023 national registry data. SOK subtypes included: donor age >60, ultimate cold ischemia time >24 h, hepatitis C positive, terminal serum creatinine >2.0 mg/dL, donation after circulatory death, kidney donor profile index >85%, and public health service increased risk donors. Gini coefficient (Gini) was used to analyze inequality in DDKT utilization by SOK subtype. Multilevel logistic regression models were used to calculate the median odds ratio (mOR), measuring center-level variation in accepting SOK donor offers among adult centers. RESULTS/UNASSIGNED:Of all DDKTs, 72.6% were from donors with at least 1 SOK characteristic. Inequality persisted in utilization of SOK DDKTs (Gini of all SOKs: 0.53, Gini of all non-SOKs: 0.47). The 193 adult centers accepted a median (interquartile range) of 12.5% (8.4%-19.2%) offered non-SOK donors and 7.2% (4.6%-10.8%) offered SOK donors. Non-SOK donors and SOK donors were refused by a median (interquartile range) of 5 (3-10) and 9 (4-23) centers, respectively. The SOK subtypes with the least and the most center-level variance in acceptance were increased risk donor (mOR = 2.06) and cold ischemia time >36 h (mOR = 4.86), respectively. CONCLUSIONS/UNASSIGNED:Centers vary sharply in their willingness to accept certain types of SOK offers. Informing centers of their patterns of accepting specific donor phenotypes compared with their peers may motivate centers to accept more SOKs for clinically suitable recipients, thus improving patient access to DDKT.

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:Kidney transplant recipients are at risk for adverse health outcomes. Digital health tools such as wearable accelerometers and continuous glucose monitors (CGMs) can provide detailed, noninvasive tracking of health behaviors and measures, such as physical activity, sleep, and glucose levels, that may offer insights into future health concerns, such as posttransplant diabetes mellitus, cognitive health, and transplant rejection. However, there is limited evidence on the feasibility and acceptability of these devices in kidney transplant candidates older than 50 y. METHODS/UNASSIGNED:This observational cross-sectional pilot study aimed to examine the feasibility of 2 digital health tools: an accelerometer and a continuous glucose monitor. Participants were eligible for the study if they were living donor kidney transplant candidates, aged 50 y or older, had no known cognitive impairments, and could provide informed consent. Participants were asked to wear a CGM and an accelerometer for up to 14 d before their kidney transplant surgery. Device feasibility was quantified by (1) the total time the devices were worn, and (2) the validated System Usability Scale survey administered after the devices were returned. RESULTS/UNASSIGNED:20 participants enrolled in the study (mean age 64 ± 9 y, 25% women, 40% with type 2 diabetes). The median number of days of accelerometer and CGM wear were 7 (interquartile range, 6-10) d and 7 (interquartile range, 7-10) d, respectively. Ninety percent of participants reported a favorable opinion of both devices. Participants wore the CGM 100% of the time and the accelerometer 90% of the time, indicating high adherence. CONCLUSIONS/UNASSIGNED:The use of digital devices was acceptable among kidney transplant candidates aged older than 50 y, paving the way for larger studies to identify early digital biomarkers of health outcomes in this high-risk population.

INTRODUCTION/BACKGROUND:Following implementation of the U.S. Kidney Allocation System (KAS) in 2014, deceased donor kidneys with a kidney donor profile index (KDPI) < 35% are prioritized for allocation to pediatric candidates. Early post-KAS data suggested this prioritization may have led to more frequent delayed graft function compared to pre-KAS, when pediatric allocation priority was based on donor age < 35 years. We sought to understand the impact of this allocation change on longer-term pediatric kidney transplant outcomes. METHODS:We used SRTR data to identify all deceased donor kidney transplants with pediatric recipients during two eras: "Pre-KAS" (12/1/2009-11/30/2014) and "KAS" (12/1/2015-11/30/2020). We used Cox proportional hazards models to calculate the association between study era and all-cause graft failure (graft failure or death) after adjusting for recipient characteristics. RESULTS:, p = 0.001). Results were similar in sensitivity analyses limited to recipients < 10 years old and recipients alive with a functioning graft 90 days post-transplant. CONCLUSIONS:KDPI-based prioritization of kidneys for pediatric allocation was associated with a lower risk of graft failure compared to donor age-based prioritization. Further refining donor risk scores may enable additional improvements in graft survival.

Historically, liver transplant (LT) candidates with human immunodeficiency virus (HIV) have experienced high waitlist mortality. Since the HIV Organ Policy Equity (HOPE) Act expands access to organs from donors with HIV, we assessed the impact of HOPE on LT rate and wait time for this population. We linked data from a multicenter HOPE in Action study to Scientific Registry of Transplant Recipients (February 21, 2019 to June 1, 2024) and used Poisson regression to compare transplant rates among 99 candidates willing to accept HOPE donors (HOPE candidates) to 13 495 candidates with or without HIV not listed as willing to accept HOPE donors (non-HOPE candidates) matched on transplant center. The median time to any deceased donor liver transplant (DDLT) was 2.3 months for HOPE and 1.1 years for non-HOPE candidates. Within 2 years of listing, 90.9% of HOPE versus 58.5% of non-HOPE candidates received a DDLT (P < .001). HOPE was associated with an overall 3.11-fold higher DDLT incident rate ratio (95% CI 2.48-3.88, P < .001). Stratified by model for end-stage liver disease score categories 6 to 14, 15 to 24, 25 to 34, and 35 to 40/status 1; HOPE candidates had 10.12-fold, 5.31-fold, 1.41-fold and 2.90-fold higher DDLT rates, respectively. Willingness to accept livers from donors with HIV improves access to liver transplantation for candidates with HIV.

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.

INTRODUCTION/BACKGROUND:Elevated concentrations of air pollutants in residential neighborhoods are associated with poorer survival, cognitive, and cardiovascular health among older adults. Older kidney transplant (KT) recipients may be more vulnerable due to chronic immunosuppression and age-related co-morbidities. Therefore, we quantified the associations between pollutant concentrations and post-KT outcomes among older recipients. METHODS:]) were obtained from the Center for Air, Climate and Energy Solutions, and matched by ZIP code and year of KT. We used shared frailty models (cluster = state) to estimate the adjusted hazard ratios (aHR) of mortality and death-censored graft failure (DCGF) and competing risk models with cluster-robust standard errors to estimate the adjusted subhazard ratios (aSHR) of dementia and stroke by pollutant concentrations. RESULTS:concentrations were associated with a 3% (aSHR = 1.03, 95% CI: 1.00-1.07) and 4% higher risk of stroke (aSHR = 1.04, 95% CI: 1.02-1.07), respectively. CONCLUSION/CONCLUSIONS:Residence in neighborhoods with high concentrations of ambient air pollutants can worsen patient and graft survival, as well as increase the risk of stroke among older KT recipients. Early screening and interventions targeting older recipients living in such neighborhoods may be crucial for preserving cognitive and cerebrovascular health, as well as improving longitudinal quality of life.

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.

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.