Rationale & Objective: Patients who are ineligible for transplant may benefit from the resources of palliative care (PC) and advance care planning. No studies have explored the appropriateness or timing of discussions of PC and planning for future medical needs at the transplant center with patients for whom transplant is not an option. We aimed to assess the perspectives of providers who refer and evaluate patients for kidney transplantation, transplant-ineligible patients, and their family caregivers on the potential role of the transplant center in incorporating PC and advance care planning for transplant-ineligible patients. Study Design: Single-center qualitative study using semistructured interviews. Setting & Participants: We enrolled 12 providers (9 transplant, 3 referring nephrologists) employed at a high-volume Southeastern transplant center, 7 patients who had been determined not to be candidates for kidney transplant between 2017 and 2023, and 3 of their caregivers. Analytical Approach: Semistructured interviews were conducted, audio-recorded, and professionally transcribed. Thematic analysis was used to identify major themes and subthemes. Results: Provider participants were 33% women, 42% minority race/ethnicity, and had practiced for a median of 9 years. Patients and caregivers were all Black/African American, 60% women, and of a median age of 66.5 years. Interviews yielded 3 major themes: (1) preparation can influence both provider delivery and patient receipt of the transplant candidacy decision; (2) knowledge gaps, lack of relationship, and disjointed care pose barriers to effective communication of transplant candidacy and subsequent options; and (3) patients and their families desire to be empowered to actively engage in planning for future health care needs. Limitations: Single-center study, homogeneous patient and caregiver population. Conclusions: Opportunities exist to expand provider and patient preparation, enhance understanding of supportive care resources and care coordination, and improve the experience for patients and their families as they cope with the decision of transplant ineligibility.

Uterine natural killer (uNK) cells are a tissue-resident lymphocyte population critical for pregnancy success. Although mouse models have demonstrated that uNK cell deficiency results in abnormal placentation and poor pregnancy outcomes, the generalizability of this knowledge to humans remains unclear. Here, we compared tissue samples collected from a cohort of human recipients of uterus transplant (UTx) at high risk for pregnancy complications with healthy controls using flow cytometry, immunofluorescence microscopy, and single-cell RNA sequencing (scRNA-seq). Subsets of tissue-resident uNK cells were reduced in endometrial and decidual samples from recipients of UTx compared with healthy control samples. Loss of tissue-resident uNK cells was associated with histopathologic evidence of maternal vascular malperfusion in placentas from recipients of UTx and related pregnancy complications including preeclampsia. scRNA-seq of UTx endometrial biopsies and deciduae further revealed that the NK cell reduction in recipients of UTx correlated with impaired transcriptional programming of NK tissue residency arising from the inhibition of signaling by nuclear factor of activated T cells (NFAT). In vitro culture of uNK cells from healthy controls with the NFAT inhibitor tacrolimus resulted in down-regulation of adhesion molecules. Together, these experiments suggested that NFAT-dependent genes modulate multiple molecular tissue residency programs in uNK cells, including early residency programs involving activator protein-1 (AP-1) family transcription factors and later residency programs characterized by up-regulation of surface integrins by transforming growth factor-β (TGF-β). Collectively, these data identify a previously undescribed role for NFAT in uNK tissue residency and provide mechanistic insights into the biologic basis of pregnancy complications due to alteration of tissue-resident NK cell subsets in humans.

Genetically engineered (GE) porcine kidney xenografts have been used recently in pig-to-human brain-dead decedent xenotransplantation. However, immunofluorescence (IF) and electron microscopy (EM) findings of xenografts have not been fully described. Here we report novel IF and EM features of GE pigs with 10 genetic modifications (10GE) xenografts with clinical correlation in 3 cases of pig-to-human brain-dead decedent xenotransplantation, performed at our institution. Preimplant biopsies unexpectedly demonstrated clinically silent mesangial immune complex deposits in all 3 xenografts, indicating porcine donor-related process. In addition, EM showed intact podocyte foot processes in the absence of endothelial cell injury, and thin glomerular basement membrane relative to adult human glomeruli in the absence of hematuria in donor pigs, likely reflecting normal porcine anatomy. In a third decedent with nephrotic-range proteinuria, foot process effacement did not correlate with the severity of proteinuria. We believe that these findings in 10GE porcine kidney xenografts may serve as a reference for normal xenograft morphology, contribute to establish xenograft rejection criteria, and support genuine need for phase I clinical trials to fully understand the long-term clinical implications of these findings.

INTRODUCTION:Parathyroidectomy is the definitive treatment for tertiary hyperparathyroidism post-kidney transplantation. However, cinacalcet-based medical management is increasingly used as an alternative. The financial consequences of each treatment remain unclear. We aimed to identify the most cost-effective strategy for managing hyperparathyroidism from the kidney transplantation recipient's perspective. METHODS:We constructed a patient-level discrete event simulation model to compare parathyroidectomy and cinacalcet-based medical management. The effects of hyperparathyroidism on allograft survival and all-cause mortality were considered in the discrete event simulation model with a time horizon of 15 years. Our base case was a 55-year-old kidney transplantation recipient with persistent hyperparathyroidism and hypercalcemia. The primary outcome was the cost-effectiveness measured by cost per quality-adjusted life years. RESULTS:The monthly out-of-pocket cost of cinacalcet ranged from $12 to $288, depending on insurance coverage, with a base case cost of $150. Our base case analysis showed that parathyroidectomy was the dominant treatment with lesser cost ($1,315 vs $7,147) and greater effectiveness (3.17 quality-adjusted life years and 2.92 quality-adjusted life years) than cinacalcet. One-way sensitivity analysis on the cinacalcet treatment duration showed that parathyroidectomy became more cost-effective at 9 months. Two-way sensitivity analysis on the cost of cinacalcet and the duration of treatment with cinacalcet showed that as the monthly cost of cinacalcet increases, the expense of cinacalcet-based medical management quickly exceeds the cost of parathyroidectomy. CONCLUSION:Parathyroidectomy becomes more cost-effective for kidney transplantation recipients with tertiary hyperparathyroidism when they require cinacalcet-based medical management for more than 9 months. As part of shared decision-making, it is important to discuss the financial costs involved in treating tertiary hyperparathyroidism.

Non-human primates and decedent humans have emerged as the two principal translational models in xenotransplantation. Each model has differing advantages and drawbacks. In this manuscript, we will compare and contrast the relative strengths of each model, focusing on the physiologic function of the xenograft in a human decedent or non-human primate. Additionally, we will discuss the pharmacologic agents typically employed in each model, highlighting both the ability of the decedent model to test clinically-relevant medication strategies that may be impossible in non-human primates due to species-specificity.

Background: Over 45% of people with HIV (PWH) in the United States at least 50 years old and are at heightened risk of aging-related comorbidities including end-stage kidney disease (ESKD), for which kidney transplant is the optimal treatment. Among ESKD patients, PWH have lower likelihood of waitlisting, a requisite step in the transplant process, than individuals without HIV. It is unknown what proportion of the inequity by HIV status can be explained by demographics, medical characteristics, substance use history, and geography. Methods: The United States Renal Data System, a national database of all individuals ESKD, was used to create a cohort of people with and without HIV through Medicare claims linkage (2007–2017). The primary outcome was waitlisting. Inverse odds ratio weighting was conducted to assess what proportion of the disparity by HIV status could be explained by individual characteristics. Results: Six thousand two hundred and fifty PWH were significantly younger at ESKD diagnosis and more commonly Black with fewer comorbidities. PWH were more frequently characterized as using tobacco, alcohol and drugs. Positive HIV-status was associated with 57% lower likelihood of waitlisting [adjusted hazard ratio (aHR): 0.43, 95% confidence interval (CI): 0.46–0.48, P < 0.001]. Controlling for demographics, medical characteristics, substance use and geography explained 39.8% of this observed disparity (aHR: 0.69, 95% CI: 0.59–0.79, P < 0.001). Conclusion: PWH were significantly less likely to be waitlisted, and 60.2% of that disparity remained unexplained. HIV characteristics such as CD4 + counts, viral loads, antiretroviral therapy adherence, as well as patient preferences and provider decision-making warrant further study.

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BACKGROUND:Hyperparathyroidism (HPT) and malignancy are the most common causes of hypercalcemia. Among kidney transplant (KT) recipients, hypercalcemia is mostly caused by tertiary HPT. Persistent tertiary HPT after KT is associated with allograft failure. Previous studies on managing tHPT were subjected to survivor treatment selection bias; as such, the impact of tertiary HPT treatment on allograft function remained unclear. We aim to assess the association between hypercalcemic tertiary HPT treatment and kidney allograft survival. MATERIALS AND METHODS:We identified 280 KT recipients (2015-2019) with elevated post-KT adjusted serum calcium and parathyroid hormone (PTH). KT recipients were characterized by treatment: cinacalcet, parathyroidectomy, or no treatment. Time-varying Cox regression with delayed entry at the time of first elevated post-KT calcium was conducted, and death-censored and all-cause allograft failure were compared by treatment groups. RESULTS:Of the 280 recipients with tHPT, 49 underwent PTx, and 98 received cinacalcet. The median time from KT to first elevated calcium was 1 month (IQR: 0-4). The median time from first elevated calcium to receiving cinacalcet and parathyroidectomy was 0(IQR: 0-3) and 13(IQR: 8-23) months, respectively. KT recipients with no treatment had shorter dialysis vintage (P = .017) and lower PTH at KT (P = .002), later onset of hypercalcemia post-KT (P < .001). Treatment with PTx (adjusted hazard ratio (aHR) = 0.18, 95%CI 0.04-0.76, P = .02) or cinacalcet (aHR = 0.14, 95%CI 0.004-0.47, P = .002) was associated with lower risk of death-censored allograft failure. Moreover, receipt of PTx (aHR = 0.28, 95%CI 0.12-0.66, P < .001) or cinacalcet (aHR = 0.38, 95%CI 0.22-0.66, P < .001) was associated with lower risk of all-cause allograft failure. CONCLUSIONS:This study demonstrates that treatment of hypercalcemic tertiary HPT post-KT is associated with improved allograft survival. Although these findings are not specific to hypercalcemia of malignancy, they do demonstrate the negative impact of hypercalcemic tertiary HPT on kidney function. Hypercalcemic HPT should be screened and aggressively treated post-KT.

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages expressed genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft was detected. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

BACKGROUND: Live donor kidney transplantation has been popularized to help mitigate the organ shortage crisis. At the time of living donor nephrectomy, living donors lose 50% of their kidney function or glomerular filtration rate (GFR). Studies have shown that in healthy living donors, the remaining kidney is able to adapt and recover 10% to 25% of postdonation lost GFR. GFR recovery is critical to long-term kidney health, particularly for Black Americans who disproportionately suffer from kidney disease with an incidence 2.5 times White Americans. To date, no study has examined whether health inequities in renal recovery postdonation exist. STUDY DESIGN: We retrospectively analyzed 100,121 living kidney donors reported to the Scientific Registry of Transplant Recipients between 1999 and 2021. We estimated GFR (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration 2021 equation and predicted the likelihood (logistic regression) and time (Cox regression) to recovery of 60% and 75% predonation eGFR. Models adjusted for age, sex, race, BMI, and predonation eGFR. RESULTS: Black patients were 47% (adjusted odds ratio 0.53, 95% CI 0.50 to 0.56, p < 0.001) and 43% (adjusted odds ratio 0.57, 95% CI 0.54 to 0.60, p < 0.001) less likely to recover 60% and 75% of predonation eGFR, respectively, compared with their White counterparts. The hazard ratio for time to renal recovery of 60% and 75% of predonation eGFR was 22% (adjusted hazard ratio 0.78, 95% CI 0.76 to 0.80, p < 0.001) and 38% (adjusted hazard ratio 0.62, 95% CI 0.60 to 0.65, p < 0.001) lower, respectively, than White patients. CONCLUSIONS: Black living kidney donors were less likely to recover predonation eGFR, and time to renal recovery was significantly longer than their White counterparts. These data highlight the need for enhanced living kidney donor follow-up, particularly for Black living kidney donors who are at greatest future risk of end-stage kidney disease.

Key Points Among obese living kidney donors, year of donation, preoperative body mass index, hypertension, and center percent of living kidney donor transplants were associated with required predonation weight loss. There were no significant differences in the likelihood of predonation weight loss requirement by race, sex, or age or by markers of preoperative metabolic dysfunction. Background The proportion of overweight/mildly obese living kidney donors (OLKDs) has increased in the past few decades, with significant center variation in the body mass index (BMI) of LKDs. The purpose of this study was to examine factors associated with required predonation weight loss among OLKDs (BMI, ≥30 kg/m 2 ). Methods This retrospective cohort study surveyed 1097 OLKDs (1979–2020) (mean BMI, 33 kg/m 2 ) about their donation experience. Bivariate analyses compared donor demographic and center characteristics by whether the donor reported predonation weight loss requirement. Generalized estimating equations with logit link were used to estimate marginal effects of patient-level and center-level factors. Multiple imputation using chained equations was implemented to account for missing values. Results Of 1097 OLKDs surveyed, 340 (31.0%) reported predonation weight loss requirement. Donors with a predonation weight loss requirement had slightly higher predonation BMIs and donated in more recent years at centers performing a lower percentage of living donor nephrectomies and with a lower median BMI. In multivariable logistic regression analysis, we observed transplant year (odds ratio [OR], 1.04 per year donation; 95% confidence interval [CI], 1.01 to 1.07; P = 0.005), preoperative BMI (OR, 1.16; 95% CI, 1.05 to 1.28; P < 0.01), preoperative hypertension (OR, 1.61; 95% CI, 1.08 to 2.40; P = 0.02), and center percentage of living donor kidney transplants (OR, 0.99; 95% CI, 0.98 to 1.00; P = 0.02) as significantly associated with a predonation weight loss requirement. The study found no differences in the likelihood of predonation weight loss requirement by race, sex, age, preoperative creatinine, preoperative metabolic dysfunction, or center-level median BMI of living donors. Conclusions These results suggest that both center-level and patient-level factors influence whether OLKDs are required to lose weight before donation. Future study is needed to determine whether predonation weight loss is associated with improved long-term postdonation outcomes.

Objective:This study was undertaken to evaluate the role of regional social vulnerability in geographic disparity for patients listed for liver transplantation with non-hepatocellular carcinoma (HCC) model for end-stage liver disease (MELD) exceptions.Summary and Background:Prior work has demonstrated regional variability in the appropriateness of MELD exceptions for diagnoses other than HCC.Methods:Adults listed at a single center for first-time liver-only transplantation without HCC after June 18, 2013 in the Scientific Registry of Transplant Recipients database as of March 2021 were examined. Candidates were mapped to hospital referral regions (HRRs). Adjusted likelihood of mortality and liver transplantation were modeled. Advantaged HRRs were defined as those where exception patients were more likely to be transplanted, yet no more likely to die in adjusted analysis. The Centers for Disease Control's Social Vulnerability Index (SVI) was used as the measure for community health. Higher SVIs indicate poorer community health.Results:There were 49,494 candidates in the cohort, of whom 4337 (8.8%) had MELD exceptions. Among continental US HRRs, 27.3% (n = 78) were identified as advantaged. The mean SVI of advantaged HRRs was 0.42 versus 0.53 in nonadvantaged HRRs (P = 0.002), indicating better community health in these areas. Only 25.3% of advantaged HRRs were in spatial clusters of high SVI versus 40.7% of nonadvantaged HRRs, whereas 44.6% of advantaged HRRs were in spatial clusters of low SVI versus 38.0% of nonadvantaged HRRs (P = 0.037).Conclusions:An advantage for non-HCC MELD exception patients is associated with lower social vulnerability on a population level. These findings suggest assigning similar waitlist priority to all non-HCC exception candidates without considering geographic differences in social determinants of health may actually exacerbate rather than ameliorate disparity.