A radical solution is needed for the organ supply crisis, and the domestic pig is a promising organ source. In preparation for a clinical trial of xenotransplantation, we developed an in vivo pre‐clinical human model to test safety and feasibility tenets established in animal models. After performance of a novel, prospective compatible crossmatch, we performed bilateral native nephrectomies in a human brain‐dead decedent and subsequently transplanted two kidneys from a pig genetically engineered for human xenotransplantation. The decedent was hemodynamically stable through reperfusion, and vascular integrity was maintained despite the exposure of the xenografts to human blood pressure. No hyperacute rejection was observed, and the kidneys remained viable until termination 74 h later. No chimerism or transmission of porcine retroviruses was detected. Longitudinal biopsies revealed thrombotic microangiopathy that did not progress in severity, without evidence of cellular rejection or deposition of antibody or complement proteins. Although the xenografts produced variable amounts of urine, creatinine clearance did not recover. Whether renal recovery was impacted by the milieu of brain death and/or microvascular injury remains unknown. In summary, our study suggests that major barriers to human xenotransplantation have been surmounted and identifies where new knowledge is needed to optimize xenotransplantation outcomes in humans.
Determining candidacy for live kidney donation among obese individuals remains challenging. Among healthy non-donors, body mass index (BMI) above 30 is associated with a 16% increase in risk of end-stage renal disease (ESRD). However, the impact on the ESRD risk attributable to donation and living with only one kidney remains unknown. Here we studied the risk of ESRD associated with obesity at the time of donation among 119 769 live kidney donors in the United States. Maximum follow-up was 20 years. Obese (BMI above 30) live kidney donors were more likely male, African American, and had higher blood pressure. Estimated risk of ESRD 20 years after donation was 93.9 per 10 000 for obese; significantly greater than the 39.7 per 10 000 for non-obese live kidney donors. Adjusted for age, sex, ethnicity, blood pressure, baseline estimated glomerular filtration rate , and relationship to recipient, obese live kidney donors had a significant 86% increased risk of ESRD compared to their non-obese counterparts (adjusted hazard ratio 1.86; 95% confidence interval 1.05–3.30). For each unit increase in BMI above 27kg/m2 there was an associated significant 7% increase in ESRD risk (1.07, 1.02–1.12). The impact of obesity on ESRD risk was similar for male and female donors, African American and Caucasian donors, and across the baseline estimated glomerular filtration rate spectrum. These findings may help to inform selection criteria and discussions with persons considering living kidney donation.
Our findings highlight the need for additional study to better understand disparities in access to kidney transplantation, particularly living donor kidney transplantation, among HIV+ kidney waitlist candidates.
Background The objective of this study was to assess the feasibility, acceptability, and potential efficacy of ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone—a lay navigator‐led, early palliative care telehealth intervention for African American/Black and/or rural‐dwelling family caregivers of individuals with advanced cancer (ClinicalTrials.gov identifier NCT03464188). Methods This was a pilot randomized trial (November 2019 to March 2021). Family caregivers of patients with newly diagnosed, stage III/IV, solid‐tumor cancers were randomized to receive either an intervention or usual care. Intervention caregivers were paired with a specially trained lay navigator who delivered 6 weekly, 20‐minute to 60‐minute telehealth coaching sessions plus monthly follow‐up for 24 weeks, reviewing skills in stress management, self‐care, getting help, staying organized, and future planning. Feasibility was assessed according to the completion of sessions and questionnaires (predefined as a completion rate ≥80%). Acceptability was determined through intervention participants' ratings of their likelihood of recommending the intervention. Measures of caregiver distress and quality of life were collected at 8 and 24 weeks. Results Sixty‐three family caregivers were randomized (usual care, n = 32; intervention, n = 31). Caregivers completed 65% of intervention sessions and 87% of questionnaires. Average ratings for recommending the program were 9.4, from 1 (not at all likely) to 10 (extremely likely). Over 24 weeks, the mean ± SE Hospital Anxiety and Depression Scale score improved by 0.30 ± 1.44 points in the intervention group and worsened by 1.99 ± 1.39 points in the usual care group (difference, −2.29; Cohen d, −0.32). The mean between‐group difference scores in caregiver quality of life was −1.56 (usual care − intervention; d, −0.07). Similar outcome results were observed for patient participants. Conclusions The authors piloted ENABLE Cornerstone, an intervention for African American and rural‐dwelling advanced cancer family caregivers. The acceptability of the intervention and data collection rates were high, and the preliminary efficacy for caregiver distress was promising. Lay Summary To date, very few programs have been developed to support under‐resourced cancer family caregivers. To address this need, the authors successfully pilot tested an early palliative care program, called Educate, Nurture, Advise, Before Life Ends (ENABLE) Cornerstone, for African American and rural family caregivers of individuals with advanced cancer. Cornerstone is led by specially trained lay people and involves a series of weekly phone sessions focused on coaching caregivers to manage stress and provide effective support to patients with cancer. The authors are now testing Cornerstone in a larger trial. If the program demonstrates benefit, it may yield a model of caregiver support that could be widely implemented.
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