Treatment of Hypercalcemic Hyperparathyroidism After Kidney Transplantation Is Associated With Improved Allograft Survival.

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.

Change in Body Mass Index and Attributable Risk of New-Onset Hypertension Among Obese Living Kidney Donors.

OBJECTIVE: To examine whether body mass index (BMI) changes modify the association between kidney donation and incident hypertension. BACKGROUND: Obesity increases hypertension risk in both general and living kidney donor (LKD) populations. Donation-attributable risk in the context of obesity, and whether weight change modifies that risk, is unknown. METHODS: Nested case-control study among 1558 adult LKDs (1976-2020) with obesity (median follow-up: 3.6 years; interquartile range: 2.0-9.4) and 3783 adults with obesity in the Coronary Artery Risk Development in Young Adults (CARDIA) and Atherosclerosis Risk in Communities (ARIC) studies (9.2 y; interquartile range: 5.3-15.8). Hypertension incidence was compared by donor status using conditional logistic regression, with BMI change investigated for effect modification. RESULTS: Overall, LKDs and nondonors had similar hypertension incidence [incidence rate ratio (IRR): 1.16, 95% confidence interval (95% CI): 0.94-1.43, P =0.16], even after adjusting for BMI change (IRR: 1.25, 95% CI: 0.99-1.58, P =0.05). Although LKDs and nondonors who lost >5% BMI had comparable hypertension incidence (IRR: 0.78, 95% CI: 0.46-1.34, P =0.36), there was a significant interaction between donor and >5% BMI gain (multiplicative interaction IRR: 1.62, 95% CI: 1.15-2.29, P =0.006; relative excess risk due to interaction: 0.90, 95% CI: 0.24-1.56, P =0.007), such that LKDs who gained weight had higher hypertension incidence than similar nondonors (IRR: 1.83, 95% CI: 1.32-2.53, P <0.001). CONCLUSIONS: Overall, LKDs and nondonors with obesity had similar hypertension incidence. Weight stability and loss were associated with similar hypertension incidence by donor status. However, LKDs who gained >5% saw increased hypertension incidence versus similar nondonors, providing support for counseling potential LKDs with obesity on weight management postdonation.

Family caregiver roles and challenges in assisting patients with cancer treatment decision-making: Analysis of data from a national survey.

BACKGROUND: We aimed to describe the roles and challenges of family caregivers involved in patients' cancer treatment decision-making. METHODS: Family caregiver-reported data were analyzed from a national survey conducted in the United States by CancerCare® (2/2021-7/2021). Four select-all-that-apply caregiver roles were explored: (1) observer (patient as primary decision-maker); (2) primary decision-maker; (3) shared decision-maker with patient and (4) decision delegated to healthcare team. Roles were compared across five treatment decisions: where to get treatment, the treatment plan, second opinions, beginning treatment and stopping treatment. Ten challenges faced by caregivers (e.g., information, cost, treatment understanding) were then examined. χ2 and regression analyses were used to assess associations between roles, decision areas, challenges and caregiver sociodemographics. RESULTS: Of 2703 caregiver respondents, 87.6% reported involvement in patient decisions about cancer treatment, including 1661 who responded to a subsection further detailing their roles and challenges with specific treatment decisions. Amongst these 1661 caregivers, 22.2% reported an observing role, 21.3% a primary decision-making role, 53.9% a shared decision-making role and 18.1% a role delegating decisions to the healthcare team. Most caregivers (60.4%) faced ≥1 challenge, the most frequent being not knowing how treatments would affect the patient's physical condition (24.8%) and quality of life (23.2%). In multivariable models, being Hispanic/Latino/a was the strongest predictor of facing at least one challenge (b = -0.581, Wald = 10.69, p < .01). CONCLUSIONS: Most caregivers were involved in patients' cancer treatment decisions. The major challenge was not understanding how treatments would impact patients' physical health and quality of life. Challenges may be more commonly faced by Hispanic/Latino/a caregivers. PATIENT OR PUBLIC CONTRIBUTION: The CancerCare® survey was developed in partnership with caregiving services and research experts to describe the role of cancer family caregivers in patient decision-making and assess their needs for support. All survey items were reviewed by a CancerCare advisory board that included five professional patient advocates and piloted by a CancerCare social worker and other staff who provide counselling to cancer caregivers.

A lay navigator-led, early palliative care intervention for African American and rural family caregivers of individuals with advanced cancer (Project Cornerstone): Results of a pilot randomized trial.

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.

First clinical-grade porcine kidney xenotransplant using a human decedent model.

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.

Donor-reported barriers to living kidney donor follow-up.

BACKGROUND: Despite regulations mandating follow-up laboratory testing for living kidney donors, less than half of transplant centers are in compliance. We sought to understand barriers to follow-up testing from the donors' perspective. METHODS: We surveyed our center's living kidney donors. Binary logistic regression was used to assess factors associated with follow-up testing completion. RESULTS: Of 185 living kidney donors, 110 (59.4%) participated. Among them, 82 (74.5%) completed 6-month laboratory testing, 76 (69.1%) completed 12-month testing, 68 (61.8%) completed both, and 21 (19.0%) completed neither. Six-month testing completion was strongly associated with 12-month testing completion (OR 9.74, 95%CI: 2.23-42.50; p = .002). Those who disagreed with the statements, "Getting labs checked wasn't a priority for me," (OR for completing 6-month testing: 15.05, 95%CI: 3.70-61.18; p < .001; OR for completing 12-month testing: 5.85, 95%CI: 1.94-17.63; p = .002); and, "I forgot to get labs drawn [until I was reminded]" (OR for completing 6-month testing: 6.93, 95%CI: 1.59-30.08; p = .01; OR for completing 12-month testing: 6.55, 95%CI: 1.98-21.63; p = .002) were more likely to complete testing. CONCLUSIONS: To our knowledge, this is the only study providing perspective on donor insights regarding the need for follow-up testing post donation. Interventions to influence living donor attitudes toward follow-up testing may improve follow-up.

Resilience, preparedness, and distress among family caregivers of patients with advanced cancer.

OBJECTIVE: Resilience has been proposed as a primary factor in how many family caregivers of patients with advanced cancer are able to resist psychological strain and perform effectively in the role while bearing a high load of caregiving tasks. To evaluate this hypothesis, we examined whether self-perceived resilience is associated with distress (anxiety and depressive symptoms), caregiver preparedness, and readiness for surrogate decision-making among a racially diverse sample of family caregivers of patients with newly diagnosed advanced cancer. METHODS: Secondary analysis of baseline data from two small-scale, pilot clinical trials that both recruited family caregivers of patients with newly diagnosed advanced cancer. Using multivariable linear regression, we analyzed relationships of resilience as a predictor of mood, caregiving preparedness, and readiness for surrogate decision-making, controlling for sociodemographics. RESULTS: Caregiver participants (N = 112) were mean 56 years of age and mostly female (76%), the patient's spouse/partner (52%), and White (56%) or African-American/Black (43%). After controlling for demographics, standardized results indicated that higher resilience was relevantly associated with higher caregiver preparedness (beta = .46, p < .001), higher readiness for surrogate decision-making (beta = .20, p < .05) and lower anxiety (beta = - .19, p < .05), and depressive symptoms (beta = - .20, p < .05). CONCLUSIONS: These results suggest that resilience may be critical to caregivers' abilities to manage stress, be effective sources of support to patients, and feel ready to make future medical decisions on behalf of patients. Future work should explore and clinicians should consider whether resilience can be enhanced in cancer caregivers to optimize their well-being and ability to perform in the caregiving and surrogate decision-making roles.

Redefining the Influence of Ethnicity on Simultaneous Kidney and Pancreas Transplantation Outcomes: A 15-year Single-center Experience.

OBJECTIVE: To examine the largest single-center experience of simultaneous kidney/pancreas transplantation (SPK) transplantation among African-Americans (AAs). BACKGROUND: Current dogma suggests that AAs have worse survival following SPK than white recipients. We hypothesize that this national trend may not be ubiquitous. METHODS: From August 30, 1999, through October 1, 2014, 188 SPK transplants were performed at the University of Alabama at Birmingham (UAB) and 5523 were performed at other US centers. Using Kaplan-Meier survival estimates and Cox proportional hazards regression, we examined the influence of recipient ethnicity on survival. RESULTS: AAs comprised 36.2% of the UAB cohort compared with only 19.1% nationally (P < 0.01); yet, overall, 3-year graft survival was statistically higher among UAB than US cohort (kidney: 91.5% vs 87.9%, P = 0.11; pancreas: 87.4% vs 81.3%; P = 0.04, respectively) and persisted on adjusted analyses [kidney adjusted hazard ratio (aHR): 0.58, 95% confidence interval (95% CI) 0.35-0.97, P = 0.04; pancreas aHR: 0.54, 95% CI 0.34-0.85, P = 0.01]. Among the UAB cohort, graft survival did not differ between AA and white recipients; in contrast, the US cohort experienced significantly lower graft survival rates among AA than white recipients (kidney 5 years: 76.5% vs 82.3%, P < 0.01; pancreas 5 years: 72.2% vs 76.3%, P = 0.01; respectively). CONCLUSION: Among a single-center cohort of SPK transplants overrepresented by AAs, we demonstrated similar outcomes among AA and white recipients and better outcomes than the US experience. These data suggest that current dogma may be incorrect. Identifying best practices for SPK transplantation is imperative to mitigate racial disparities in outcomes observed at the national level.

Optimal timing of hepatitis C treatment among HIV/HCV coinfected ESRD patients: Pre- vs posttransplant.

Patients with end-stage renal disease (ESRD) who are coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have access to effective treatment options for HCV infection. However, they also have access to HCV-infected kidneys, which historically afford shorter times to transplantation. Given the high waitlist mortality and rapid progression of liver fibrosis among coinfected kidney-only transplant candidates, identification of the optimal treatment strategy is paramount. Two strategies, treatment pre- and posttransplant, were compared using Monte Carlo microsimulation of 1 000 000 candidates. The microsimulation was stratified by liver fibrosis stage at waitlist addition and wait-time over a lifetime time horizon. Treatment posttransplant was consistently cost-saving as compared to treatment pretransplant due to the high cost of dialysis. Among patients with low fibrosis disease (F0-F1), treatment posttransplant also yielded higher life months (LM) and quality-adjusted life months (QALM), except among F1 candidates with wait times ≥ 18 months. For candidates with advanced liver disease (F2-F4), treatment pretransplant afforded more LM and QALM unless wait time was <18 months. Moreover, treatment pretransplant was cost-effective for F2 candidates with wait times >71 months and F3 candidates with wait times >18 months. Thus, optimal timing of HCV treatment differs based on liver disease severity and wait time, favoring pretransplant treatment when cirrhosis development prior to transplant seems likely.

Mitigating Racial and Sex Disparities in Access to Living Donor Kidney Transplantation: Impact of the Nation's Longest Single-center Kidney Chain.

OBJECTIVE: In this study, we sought to assess likelihood of living donor kidney transplantation (LDKT) within a single-center kidney transplant waitlist, by race and sex, after implementation of an incompatible program. SUMMARY BACKGROUND DATA: Disparities in access to LDKT exist among minority women and may be partially explained by antigen sensitization secondary to prior pregnancies, transplants, or blood transfusions, creating difficulty finding compatible matches. To address these and other obstacles, an incompatible LDKT program, incorporating desensitization and kidney paired donation, was created at our institution. METHODS: A retrospective cohort study was performed among our kidney transplant waitlist candidates (n = 8895). Multivariable Cox regression was utilized, comparing likelihood of LDKT before (era 1: 01/2007-01/2013) and after (era 2: 01/2013-11/2018) implementation of the incompatible program. Candidates were stratified by race [white vs minority (nonwhite)], sex, and breadth of sensitization. RESULTS: Program implementation resulted in the nation's longest single-center kidney chain, and likelihood of LDKT increased by 70% for whites [adjusted hazard ratio (aHR) 1.70; 95% confidence interval (CI), 1.46-1.99] and more than 100% for minorities (aHR 2.05; 95% CI, 1.60-2.62). Improvement in access to LDKT was greatest among sensitized minority women [calculated panel reactive antibody (cPRA) 11%-49%: aHR 4.79; 95% CI, 2.27-10.11; cPRA 50%-100%: aHR 4.09; 95% CI, 1.89-8.82]. CONCLUSIONS: Implementation of an incompatible program, and the resulting nation's longest single-center kidney chain, mitigated disparities in access to LDKT among minorities, specifically sensitized women. Extrapolation of this success on a national level may further serve these vulnerable populations.

Patient Perspectives on Weight Management for Living Kidney Donation.

BACKGROUND: Living kidney donors (LKDs) with obesity have increased perioperative risks and risk of end-stage renal disease after donation. Consequently, obesity serves as a barrier to donation, as many transplant centers encourage or require weight loss before donation for obese LKD candidates. Therefore, this study sought to assess patients' perspectives on weight management strategies before donation among obese LKD candidates. We hypothesized that willingness to participate in a weight loss program may be associated with donor-recipient relationship. MATERIALS AND METHODS: Obese (BMI ≥30 kg/m2) LKD candidates evaluated at a single institution from September 2017 to August 2018 were recruited. A survey was administered to assess LKD candidates' baseline exercise and dietary habits and their interest in weight management strategies for the purpose of donation approval. Participants were grouped by relationship to the recipient (close relatives: first-degree relatives or spouses [n = 29], compared with all other relationships [n = 21]). Descriptive statistics were used to summarize the data. RESULTS: 50 of 51 obese LKD candidates who were approached completed the survey. 90% of participants expressed willingness to lose weight if necessary to become eligible for donor nephrectomy. Compared with all other LKD candidates, close relatives were more likely to be interested in combined diet and exercise programs at our institution (P = 0.01). CONCLUSIONS: Among obese LKD candidates, there was an interest in weight loss for the purposes of living kidney donation approval, particularly among close relatives of potential recipients. Future programs designed to promote weight management efforts for obese LKD candidates should be considered.

Disparity in access to kidney allograft offers among transplant candidates with human immunodeficiency virus.

BACKGROUND: Despite a survival benefit from transplantation and acceptable outcomes, patients with human immunodeficiency virus (HIV+) face barriers to kidney transplantation. Little is known about the acceptance or decline of organ offers on their behalf because waitlist registry data do not include HIV serostatus. METHODS: We performed a retrospective cohort study using match run data from the Organ Procurement and Transplantation Network, including every kidney offer from May 1, 2007, to July 3, 2013. HIV and hepatitis C virus (HCV) serostatus were obtained by merging the match run with clinical data from a large dialysis provider. We used Cox proportional hazards modeling to evaluate differences in time to the first organ offer and to transplantation. A total of 35 646 uninfected, 2213 HCV+, 418 HIV+, and 71 HIV+/HCV+ candidates received organ offers during the study period. RESULTS: Compared to uninfected candidates, HIV+ candidates had a significantly lower likelihood of receiving a first offer (adjusted hazard ratio [aHR] 0.88, 95% confidence interval [CI] 0.79-0.99) and undergoing transplantation (aHR 0.82, 95% CI: 0.68-0.98) after receiving a first offer; HCV+ candidates had a similar likelihood of receiving a first offer (aHR 0.98, 95% CI: 0.92-1.03) and greater likelihood of transplantation after receiving a first offer (aHR 1.23, 95% CI: 1.12-1.36). CONCLUSIONS: HIV+ candidates had a significantly longer wait until their first organ offer and to transplantation. Efforts to increase their access to transplantation are needed.

Population level outcomes and cost-effectiveness of hepatitis C treatment pre- vs postkidney transplantation.

Direct-acting antivirals approved for use in patients with end-stage renal disease (ESRD) now exist. HCV-positive (HCV+) ESRD patients have the opportunity to decrease the waiting times for transplantation by accepting HCV-infected kidneys. The optimal timing for HCV treatment (pre- vs posttransplant) among kidney transplant candidates is unknown. Monte Carlo microsimulation of 100 000 candidates was used to examine the cost-effectiveness of HCV treatment pretransplant vs posttransplant by liver fibrosis stage and waiting time over a lifetime time horizon using 2 regimens approved for ESRD patients. Treatment pretransplant yielded higher quality-adjusted life years (QALYs) compared with posttransplant treatment in all subgroups except those with Meta-analysis of Histological Data in Viral Hepatitis stage F0 (pretransplant: 5.7 QALYs vs posttransplant: 5.8 QALYs). However, treatment posttransplant was cost-saving due to decreased dialysis duration with the use of HCV-infected kidneys (pretransplant: $735 700 vs posttransplant: $682 400). Using a willingness-to-pay threshold of $100 000, treatment pretransplant was not cost-effective except for those with Meta-analysis of Histological Data in Viral Hepatitis stage F3 whose fibrosis progression was halted. If HCV+ candidates had access to HCV-infected donors and were transplanted ≥9 months sooner than HCV-negative candidates, treatment pretransplant was no longer cost-effective (incremental cost-effectiveness ratio [ICER]: $107 100). In conclusion, optimal timing of treatment depends on fibrosis stage and access to HCV+ kidneys but generally favors posttransplant HCV eradication.

Decreasing deceased donor transplant rates among children (≤6 years) under the new kidney allocation system.

The Kidney Allocation System (KAS) was implemented in December 2014 with unknown impact on the pediatric waitlist. To understand the effect of KAS on pediatric registrants, deceased donor kidney transplant (DDKT) rate was assessed using interrupted time series analysis and time-to-event analysis. Two allocation eras were defined with an intermediary washout period: Era 1 (01/01/2013-09/01/2014), Era 2 (09/01/2014-03/01/2015), and Era 3(03/01/2015-03/01/2017). When using Cox proportional hazards, there was no significant association between allocation era and DDKT likelihood as compared to Era 1 (Era 3: aHR: 1.07, 95% CI: 0.97-1.18, P = .17). However, this was not consistent across all subgroups. Specifically, while highly sensitized pediatric registrants were consistently less likely to be transplanted than their less sensitized counterparts, this disparity was attenuated in Era 3 (Era 1 aHR: 0.04, 95%CI: 0.01-0.14, P < .001; Era 3 aHR: 0.33, 95% CI: 0.21-0.53, P < .001) whereas the youngest registrants aged 0-6 experienced a 21% decrease in DDKT likelihood in Era 3 as compared to Era 1 (aHR: 0.79, 95% CI: 0.64-0.98, P = .03). Thus, while overall DDKT likelihood remained stable with the introduction of KAS, registrants ≤ 6 years of age were disadvantaged, warranting further study to ensure equitable access to transplantation.

Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors.

OBJECTIVE: The aim of this study was to develop a novel chronic kidney disease (CKD) risk prediction tool for young potential living kidney donors. SUMMARY OF BACKGROUND DATA: Living kidney donor selection practices have evolved from examining individual risk factors to a risk calculator incorporating multiple characteristics. Owing to limited long-term data and lack of genetic information, current risk tools lack precision among young potential living kidney donors, particularly African Americans (AAs). METHODS: We identified a cohort of young adults (18-30 years) with no absolute contraindication to kidney donation from the longitudinal cohort study Coronary Artery Risk Development in Young Adults. Risk associations for CKD (estimated glomerular filtration rate <60 mL/min/1.73 m) were identified and assigned weighted points to calculate risk scores. RESULTS: A total of 3438 healthy adults were identified [mean age 24.8 years; 48.3% AA; median follow-up 24.9 years (interquartile range: 24.5-25.2)]. For 18-year olds, 25-year projected CKD risk varied by ethnicity and sex even without baseline clinical and genetic abnormalities; risk was 0.30% for European American (EA) women, 0.52% for EA men, 0.52% for AA women, 0.90% for AA men. Among 18-year-old AAs with apolipoprotein L1 gene (APOL1) renal-risk variants without baseline abnormalities, 25-year risk significantly increased: 1.46% for women and 2.53% for men; among those with 2 APOL1 renal-risk variants and baseline abnormalities, 25-year risk was higher: 2.53% to 6.23% for women and 4.35% to 10.58% for men. CONCLUSIONS: Young AAs were at highest risk for CKD, and APOL1 renal-risk variants drove some of this risk. Understanding the genetic profile of young AA potential living kidney donors in the context of baseline health characteristics may help to inform candidate selection and counseling.

Kidney transplantation and waitlist mortality rates among candidates registered as willing to accept a hepatitis C infected kidney.

BACKGROUND: HCV-infected (HCV+) ESRD patients derive significant survival benefit from kidney transplantation (KT) over remaining on dialysis. Given high mortality rates on dialysis and the unique ability to accept HCV+ and HCV- donor kidneys, understanding their access to KT is essential. METHODS: Three thousand nine hundred and sixty-three adult kidney-only candidates reported as willing to accept an HCV+ kidney from 2008 to 2014 were identified and assumed to be HCV+. Time-at-risk began at date of listing. Cumulative incidence of transplant and waitlist mortality were assessed using competing risks, and separate mixed effects Cox proportional hazards models were used to examine waitlist mortality and transplantation rates. All models were adjusted for candidate demographic and clinical characteristics with a random effect for listing organ procurement organization with nested listing center. RESULTS: HCV+ candidates were commonly older (>50 years: 82.6%), African American (52.8%), and male (73.6%). Five years after listing, 35.5% of candidates were transplanted with an HCV+ donor kidney, 9.7% transplanted with an HCV- donor kidney, and 23.6% died on the waitlist. Overall transplant rates exceeded waitlist mortality rates (22.69 vs 11.45 per 100 person-years [PY]), largely driven by transplantation with HCV+ donor kidneys. Utilization of HCV+ donor kidneys was associated with increased transplantation rate (17.72 per 100 PY), while rate of transplant with HCV- donor kidneys was much lower (4.97 per 100 PY) than waitlist mortality (11.45 per 100 PY). CONCLUSION: In light of effective HCV therapies, it may be prudent to institute strategies to decrease waiting time and waitlist mortality for HCV+ candidates by increasing utilization of HCV+ donor kidneys.

Obesity increases the risk of end-stage renal disease among living kidney donors.

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 27 kg/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.

Survival Benefit of Kidney Transplantation in HIV-infected Patients.

OBJECTIVE: To determine the survival benefit of kidney transplantation in human immunodeficiency virus (HIV)-infected patients with end-stage renal disease (ESRD). SUMMARY BACKGROUND DATA: Although kidney transplantation (KT) has emerged as a viable option for select HIV-infected patients, concerns have been raised that risks of KT in HIV-infected patients are higher than those in their HIV-negative counterparts. Despite these increased risks, KT may provide survival benefit for the HIV-infected patient with ESRD, yet this important clinical question remains unanswered. METHODS: Data from the Scientific Registry of Transplant Recipients were linked to IMS pharmacy fills (January 1, 2001 to October 1, 2012) to identify and study 1431 HIV-infected KT candidates from the first point of active status on the waiting list. Time-dependent Cox regression was used to establish a counterfactual framework for estimating survival benefit of KT. RESULTS: Adjusted relative risk (aRR) of mortality at 5 years was 79% lower after KT compared with dialysis (aRR 0.21; 95% CI 0.10-0.42; P <0.001), and statistically significant survival benefit was achieved by 194 days of KT. Among patients coinfected with hepatitis C, aRR of mortality at 5 years was 91% lower after KT compared with dialysis (aRR 0.09; 95% CI 0.02-0.46; P < 0.004); however, statistically significant survival benefit was not achieved until 392 days after KT. CONCLUSIONS: Evidence suggests that for HIV-infected ESRD patients, KT is associated with a significant survival benefit compared with remaining on dialysis.