Health Inequity in Likelihood and Time to Renal Recovery after Living Kidney Donation: Implications for Kidney Health in Black Americans.

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.

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.

Quantifying the association of individual-level characteristics with disparities in kidney transplant waitlist addition among people with HIV.

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.

African American/Black race, apolipoprotein L1 , and serum creatinine among persons with HIV.

OBJECTIVE: Accurate estimation of kidney function is critical among persons with HIV (PWH) to avoid under-dosing of antiretroviral therapies and ensure timely referral for kidney transplantation. Existing estimation equations for kidney function include race, the appropriateness of which has been debated. Given advancements in understanding of race and the necessity of accuracy in kidney function estimation, this study aimed to examine whether race, or genetic factors, improved prediction of serum creatinine among PWH. DESIGN: This cross-sectional study utilized data from the Center for AIDS Research Network of Integrated Clinical Systems cohort (2008-2018). The outcome was baseline serum creatinine. METHODS: Ordinary least squares regression was used to examine whether inclusion of race or genetic factors [ apolipoprotein-L1 ( APOL1 ) variants and genetic African ancestry] improved serum creatinine prediction. A reduction in root mean squared error (RMSE) greater than 2% was a clinically relevant improvement in predictive ability. RESULTS: There were 4183 PWH included. Among PWH whose serum creatinine was less than 1.7 mg/dl, race was significantly associated with serum creatinine ( ß â€Š= 0.06, SE = 0.01, P  < 0.001) but did not improve predictive ability. African ancestry and APOL1 variants similarly failed to improve predictive ability. Whereas, when serum creatinine was at least 1.7 mg/dl, inclusion of race reduced the RMSE by 2.1%, indicating improvement in predictive ability. APOL1 variants further improved predictive ability by reducing the RMSE by 2.9%. CONCLUSION: These data suggest that, among PWH, inclusion of race or genetic factors may only be warranted at higher serum creatinine levels. Work eliminating existing healthcare disparities while preserving the utility of estimating equations is needed.

Racial Disparities in Access to the Kidney Transplant Waitlist Among People with Human Immunodeficiency Virus.

The epidemiology of human immunodeficiency virus (HIV) has shifted such that Black individuals disproportionately represent incident HIV diagnoses. While risk of end-stage kidney disease (ESKD) among people with HIV (PWH) has declined with effective antiretroviral therapies, a substantial racial disparity in ESKD burden exists with the greatest prevalence among Black PWH. Disparities in waitlisting for kidney transplantation, the optimal treatment for ESKD, exist for both PWH and Black individuals without HIV, but it is unknown whether these characteristics together exacerbate such disparities. Six hundred two thousand six ESKD patients were identified from the United States Renal Data System (January 1, 2007 to December 31, 2017), and HIV-status was determined through Medicare claims. Cox proportional hazards regression was used to determine waitlisting rates. Multiplicative interaction terms between HIV-status and race were examined. The 6250 PWH were significantly younger, more commonly Black, and less commonly female than those without HIV. HIV-status and race were independently associated with 50% and 12% lower likelihood of waitlisting, respectively [adjusted hazard ratio (aHR): 0.50, 95% confidence interval (CI): 0.36-0.69, p < 0.001; aHR: 0.88, 95% CI: 0.87-0.90, p < 0.001]. There was also a significant interaction present between HIV-status and Black race (aHR: 0.80, 95% CI: 0.66-0.98, p < 0.001) such that, while HIV-status and Black race were independently associated with decreased waitlisting, the interaction of Black race and HIV-status exacerbated those disparities. While limited by lack of HIV-specific data that may impact inferences with respect to race, additional studies are urgently needed to understand the interplay between HIV risk factors, HIV-stigma, and racism, and how intersectionality may exacerbate disparities in transplantation among PWH.

Racial Disparities in Hidradenitis Suppurativa-Related Pain: A Cross-sectional Analysis.

Racial disparities in pain management for chronic diseases persist in the United States. However, no research exists assessing racial disparities in related pain. This study aimed to identify racial differences in hidradenitis suppurativa (HS)-related pain scores. Additionally, we characterized patient satisfaction with pain management. Further research is needed to evaluate if systemic or health care provider biases contribute to racial differences in HS-related pain management.

Association of FDA Mandate Limiting Acetaminophen (Paracetamol) in Prescription Combination Opioid Products and Subsequent Hospitalizations and Acute Liver Failure.

Importance: In January 2011, the US Food and Drug Administration (FDA) announced a mandate to limit acetaminophen (paracetamol) to 325 mg/tablet in combination acetaminophen and opioid medications, with manufacturer compliance required by March 2014. Objective: To assess the odds of hospitalization and the proportion of acute liver failure (ALF) cases with acetaminophen and opioid toxicity prior to and after the mandate. Design, Setting, and Participants: This interrupted time-series analysis used hospitalization data from 2007-2019 involving ICD-9/ICD-10 codes consistent with both acetaminophen and opioid toxicity from the National Inpatient Sample (NIS), a large US hospitalization database, and ALF cases from 1998-2019 involving acetaminophen and opioid products from the Acute Liver Failure Study Group (ALFSG), a cohort of 32 US medical centers. For comparison, hospitalizations and ALF cases consistent with acetaminophen toxicity alone were extracted from the NIS and ALFSG. Exposures: Time prior to and after the FDA mandate limiting acetaminophen to 325 mg in combination acetaminophen and opioid products. Main Outcomes and Measures: Odds of hospitalization involving acetaminophen and opioid toxicity and percentage of ALF cases from acetaminophen and opioid products prior to and after the mandate. Results: In the NIS, among 474 047 585 hospitalizations from Q1 2007 through Q4 2019, there were 39 606 hospitalizations involving acetaminophen and opioid toxicity; 66.8% of cases were among women; median age, 42.2 (IQR, 28.4-54.1). In the ALFSG, from Q1 1998 through Q3 2019, there were a total of 2631 ALF cases, of which 465 involved acetaminophen and opioid toxicity; 85.4% women; median age, 39.0 (IQR, 32.0-47.0). The predicted incidence of hospitalizations 1 day prior to the FDA announcement was 12.2 cases/100 000 hospitalizations (95% CI, 11.0-13.4); by Q4 2019, it was 4.4/100 000 hospitalizations (95% CI, 4.1-4.7) (absolute difference, 7.8/100 000 [95% CI, 6.6-9.0]; P < .001). The odds of hospitalizations with acetaminophen and opioid toxicity increased 11%/y prior to the announcement (odds ratio [OR], 1.11 [95% CI, 1.06-1.15]) and decreased 11%/y after the announcement (OR, 0.89 [95% CI, 0.88-0.90]). The predicted percentage of ALF cases involving acetaminophen and opioid toxicity 1 day prior to the FDA announcement was 27.4% (95% CI, 23.3%-31.9%); by Q3 2019, it was 5.3% (95% CI, 3.1%-8.8%) (absolute difference, 21.8% [95% CI, 15.5%-32.4%]; P < .001). The percentage of ALF cases involving acetaminophen and opioid toxicity increased 7% per year prior to the announcement (OR, 1.07 [95% CI, 1.03-1.1]; P < .001) and decreased 16% per year after the announcement (OR, 0.84 [95% CI, 0.77-0.92]; P < .001). Sensitivity analyses confirmed these findings. Conclusions and Relevance: The FDA mandate limiting acetaminophen dosage to 325 mg/tablet in prescription acetaminophen and opioid products was associated with a statistically significant decrease in the yearly rate of hospitalizations and proportion per year of ALF cases involving acetaminophen and opioid toxicity.

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.

Reclassification of CKD in living kidney donors with the refitted race-free eGFR formula.

BACKGROUND: Chronic Kidney Disease (CKD) Epidemiology Collaboration eGFR 2021 formula removed Black race from the 2009 equation. Unintended consequences may lead to reclassifying Black living kidney donors as having more advanced CKD, exacerbating racial disparities in living donation. METHODS: We used national data to quantify CKD stage reclassification based on eGFR for Black living donors both pre- and post-donation. RESULTS: Among 6365 Black living donors, 17.7% were reclassified as having a higher CKD stage pre-donation with the 2021 formula. Among 4149 Black living donors with at least 2 creatinine measurements post-donation, 25.5% were reclassified as having a higher CKD stage post-donation with the 2021 formula. CONCLUSION: Eliminating race in the formula may inappropriately label Black potential donors with CKD. These data highlight the need for a validated eGFR formula for donors, use of measured and not eGFR, and education of non-transplant providers regarding interpretation of CKD staging in living donation.

Diabetes-free survival among living kidney donors and non-donors with obesity: A longitudinal cohort study.

BACKGROUND: Approval of living kidney donors (LKD) with end-stage kidney disease (ESKD) risk factors, such as obesity, has increased. While lifetime ESKD development data are lacking, the study of intermediate outcomes such as diabetes is critical for LKD safety. Donation-attributable diabetes risk among persons with obesity remains unknown. The purpose of this study was to evaluate 10-year diabetes-free survival among LKDs and non-donors with obesity. METHODS: This longitudinal cohort study identified adult, LKDs (1976-2020) from 42 US transplant centers and non-donors from the Coronary Artery Risk Development in Young Adults (1985-1986) and the Atherosclerosis Risk in Communities (1987-1989) studies with body mass index ≥30 kg/m2. LKDs were matched to non-donors on baseline characteristics (age, sex, race, body mass index, systolic and diastolic blood pressure) plus diabetes-specific risk factors (family history of diabetes, impaired fasting glucose, smoking history). Accelerated failure time models were utilized to evaluate 10-year diabetes-free survival. FINDINGS: Among 3464 participants, 1119 (32%) were LKDs and 2345 (68%) were non-donors. After matching on baseline characteristics plus diabetes-specific risk factors, 4% (7/165) LKDs and 9% (15/165) non-donors developed diabetes (median follow-up time 8.5 (IQR: 5.6-10.0) and 9.1 (IQR: 5.9-10.0) years, respectively). While not significant, LKDs were estimated to live diabetes-free 2 times longer than non-donors (estimate 1.91; 95% CI: 0.79-4.64, p = 0.15). CONCLUSIONS: LKDs with obesity trended toward living longer diabetes-free than non-donors with obesity, suggesting within the decade following donation there was no increased diabetes risk among LKDs. Further work is needed to evaluate donation-attributable diabetes risk long-term.

Inter-Rater Reliability and Correlation of L1 Hounsfield Unit Measurements with DXA Scores.

INTRODUCTION: While prior studies have generally reported rigorous protocols using prespecified CT scanner settings for HU measurements, the present study sought to report on the correlation between DXA and HUs recorded using several CT scanners with varying sequences, simulating measurements performed in "real-world" hospital and Emergency Department (ED) settings. METHODOLOGY: Six raters performed HU measurements of trabecular bone at the L1 vertebral body for forty consecutive patients on Phillips and General Electric (GE) abdominal CT scans obtained between 2017 and 2021. Inter-rater reliability of the HU measurements and their correlations with recorded DXA-based bone assessments were determined. Correlation coefficients were calculated for the HU measurements between scanner vendors as well as for the CT HUs with each DXA measurement. RESULTS: The ICC for L1 HUs read on the Phillips and GE scanners were 0.85 and 0.82, respectively, indicating excellent agreement. The correlation coefficient for the mean HUs on the Phillips and GE scanners was 0.92, also indicating excellent correlation. For both scanner vendors, the HU values most closely correlated with the total femur and femoral neck T-scores. CONCLUSIONS: HU values recorded on a Phillips and GE scanner both demonstrated excellent inter-rater reliability. Correlations were strongest between L1 HU values and total femur DXA T-scores. Readily available abdominal CT image data across multiple hospital settings can be utilized by providers of varying level of imaging interpretation expertise to determine vertebral body Hounsfield units that may help identify osteoporosis risk without additional radiation exposure or cost.

Associations between female birth sex and risk of chronic kidney disease development among people with HIV in the USA: A longitudinal, multicentre, cohort study.

Background: Women represent a meaningful proportion of new HIV diagnoses, with Black women comprising 58% of new diagnoses among women. As HIV infection also increases risk of chronic kidney disease (CKD), understanding CKD risk among women with HIV (WWH), particularly Black women, is critical. Methods: In this longitudinal cohort study of people with HIV (PWH) enrolled in CFAR Network of Integrated Clinical Systems (CNICS), a multicentre study comprised of eight academic medical centres across the United States from Jan 01, 1996 and Nov 01, 2019, adult PWH were excluded if they had ≤2 serum creatinine measurements, developed CKD prior to enrollment, or identified as intersex or transgendered, leaving a final cohort of 33,998 PWH. The outcome was CKD development, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1·73 m2 calculated using the CKD-EPI equation, for ≥90 days with no intervening higher values. Findings: Adjusting for demographic and clinical characteristics, WWH were 61% more likely to develop CKD than men (adjusted hazard ratio [aHR]: 1·61, 95% CI: 1·46-1·78, p<0·001). This difference persisted after further adjustment for APOL1 risk variants (aHR female sex: 1·92, 95% CI: 1·63-2·26, p<0·001) and substance abuse (aHR female sex: 1·70, 95% CI: 1·54-1·87, p<0·001). Interpretation: WWH experienced increased risk of CKD. Given disparities in care among patients with end-stage kidney disease, efforts to engage WWH in nephrology care to improve chronic disease management are critical. Funding: US National Institutes of Health.

Perpetuating Disparity: Failure of the Kidney Transplant System to Provide the Most Kidney Transplants to Communities With the Greatest Need.

BACKGROUND: The burden of end-stage kidney disease (ESKD) and kidney transplant rates vary significantly across the United States. This study aims to examine the mismatch between ESKD burden and kidney transplant rates from a perspective of spatial epidemiology. METHODS: US Renal Data System data from 2015 to 2017 on incident ESKD and kidney transplants per 1000 incident ESKD cases was analyzed. Clustering of ESKD burden and kidney transplant rates at the county level was determined using local Moran's I and correlated to county health scores. Higher percentile county health scores indicated worse overall community health. RESULTS: Significant clusters of high-ESKD burden tended to coincide with clusters of low kidney transplant rates, and vice versa. The most common cluster type had high incident ESKD with low transplant rates (377 counties). Counties in these clusters had the lowest overall mean transplant rate (61.1), highest overall mean ESKD incidence (61.3), and highest mean county health scores percentile (80.9%, P <0.001 vs all other cluster types). By comparison, counties in clusters with low ESKD incidence and high transplant rates (n=359) had the highest mean transplant rate (110.6), the lowest mean ESKD incidence (28.9), and the lowest county health scores (20.2%). All comparisons to high-ESKD/low-transplant clusters were significant at P value <0.001. CONCLUSION: There was a significant mismatch between kidney transplant rates and ESKD burden, where areas with the greatest need had the lowest transplant rates. This pattern exacerbates pre-existing disparities, as disadvantaged high-ESKD regions already suffer from worse access to care and overall community health, as evidenced by the highest county health scores in the study.

Efficacy of hope: Analysis of organ quality and availability among deceased HIV-positive donors.

BACKGROUND: Improved survival among people with human immunodeficiency virus (HIV) (PWH) has led to increased organ failure, necessitating transplantation. In 2013, the HIV Organ Policy Equity (HOPE) Act was passed, allowing PWH to donate organs to other PWH. No study has assessed organ quality and quantity among a national pool of PWH. METHODS: CFAR Network of Integrated Clinical Systems (CNICS), a multicenter study capturing data on PWH, was used to identify 6504 deaths from 1999 to 2018. Exclusions included cause of death, chronic kidney disease, fibrosis-4 score ≥ 3.25, and opportunistic infection at the time of death. Donor quality was defined by HIV viremia and the kidney donor profile index (KDPI). The CDC Wonder database, which contains national death data, permitted the estimation of deaths among PWH nationally from 1999 to 2018. Assuming CNICS was representative of PWH nationally, percentages of potential donors were applied to the CDC Wonder cohort. RESULTS: Within CNICS, there were 3241 (65.9%) potential kidney donors and 3536 (71.9%) potential liver donors from 1999 to 2018. Based on viremia and KDPI, 821 were lower-risk kidney donors (16.7%) and 1206 (24.5%) were lower-risk liver donors. Within CDC Wonder, we identified 12 048 potential donors from 1999 to 2018. Extrapolating from CNICS to the national cohort suggested 396 kidney donors (792 kidneys) and 433 liver donors annually, with 100 kidney donors (200 kidneys) and 147 livers being lower-risk. CONCLUSION: A substantial number of PWH meet donation criteria, a valuable source of organs for PWH in need of transplants. Our estimates suggest there may be more available organs from PWH than current transplant numbers indicate.

Greater community vulnerability is associated with poor living donor navigator program fidelity.

BACKGROUND: Community-level factors contribute to living donor kidney transplantation disparities but may also influence the interventions aimed to mitigate these disparities. The Living Donor Navigator Program was designed to separate the advocacy role from the patient in need of transplantation-friends/family are encouraged to participate as the patients' advocates to identify living donors, though some of the patients participate alone as self-advocates. Self-advocates have a lower living donor kidney transplantation likelihood compared to the patients with an advocate. We sought to evaluate the relationship between the patients' community-level vulnerability and living donor navigator self-advocacy as a surrogate for program fidelity. METHODS: This single-center, retrospective study included 110 Living Donor Navigator participants (April 2017-June 2019). Program fidelity was assessed using the participants' advocacy status. Measures of community vulnerability were obtained from the Centers for Disease Control and Prevention Social Vulnerability Index. Modified Poisson regression was used to evaluate the association between community-level vulnerability and living donor navigator self-advocacy. RESULTS: Of the 110 participants, 19% (n = 21) were self-advocates. For every 10% increase in community-level vulnerability, patients had 17% higher risk of self-advocacy (adjusted relative risk 1.17, 95% confidence interval: 1.03-1.32, P = .01). Living in areas with greater unemployment (adjusted relative risk: 1.18, 95% confidence interval: 1.04-1.33, P = .01), single-parent households (adjusted relative risk: 1.23, 95% confidence interval: 1.06-1.42, P = .006), minority population (adjusted relative risk: 1.30, 95% confidence interval: 1.04-1.55, P = .02), or no-vehicle households (adjusted relative risk: 1.17, 95% confidence interval: 1.02-1.35, P = .02) were associated with increased risk of self-advocacy. CONCLUSION: Having a greater community-level vulnerability was associated with poor Living Donor Navigator Program fidelity. The potential barriers identified using the Social Vulnerability Index may direct resource allocation and program refinement to optimize program fidelity and efficacy for all participants.

Abnormal time-zero histology is predictive of kidney transplant outcomes.

INTRODUCTION: Time-zero biopsies can detect donor-derived lesions at the time of kidney transplantation, but their utility in predicting long-term outcomes is unclear under the updated Kidney Allocation System. METHODS: We conducted a single-center retrospective cohort study of 272 consecutive post-reperfusion time-zero biopsies. We tested the hypothesis that abnormal time-zero histology is a strong indicator of donor quality that increases the precision of the kidney donor profile index (KDPI) score to predict long-term outcomes. RESULTS: We detected abnormal biopsies in 42% of the cohort, which were independently associated with a 1.2-fold increased hazard for a composite of acute rejection, allograft failure, and death after adjusting for clinical characteristics including KDPI. By Kaplan-Meier analysis, the relationship between abnormal time-zero histology and the composite endpoint was only significant in the subgroup of deceased donor kidney transplants with KDPI scores >35. Abnormal time-zero histology, particularly vascular intimal fibrosis and arteriolar hyalinosis scores, was independently associated with lower 12-month estimated GFR. CONCLUSION: In conclusion, abnormal time-zero histology is relatively common and identifies a group of kidney recipients at increased risk for worse long-term outcomes. Further studies are needed to determine the optimal patient population in which to deploy time-zero biopsies as an additional surveillance tool.

Dialysis Nonadherence and Kidney Transplant Outcomes: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Concerns about nonadherent behaviors often prevent dialysis patients from entering waitlists for transplant even though there is an inconsistent association of these behaviors with posttransplant outcomes. We examined the association between plausible metrics of nonadherence related to dialysis treatment and posttransplant outcomes. STUDY DESIGN: Retrospective cohort. We linked national dialysis treatment data with transplant registry data. SETTING AND PARTICIPANTS: Adult patients receiving maintenance hemodialysis from January 1, 2004, through December 31, 2014, who received a kidney transplant at a US center. EXPOSURES: We examined 5 nonadherence metrics: serum potassium level (≥5.2 mEq/L), serum phosphorus level (>5.5 mg/dL), interdialytic weight gain (IDWG; ≥5 L), shortened treatments (≥30 min), and missed treatments (≥1); missed treatment data were available only for 2004-2009. These metrics were characterized per proportion of time under observation. Dialysis observation time was divided into 3-month intervals (quarters), and the number of nonadherent measurements in each domain was calculated for each quarter. OUTCOMES: Allograft loss, mortality, and acute rejection in the first posttransplant year. ANALYTICAL APPROACH: Using Cox proportional hazards and logistic regression, we estimated the hazard ratios for graft loss and mortality and odds ratios for rejection. RESULTS: 9,543 patients met inclusion criteria. In our primary model, hyperphosphatemia (adjusted hazard ratio [aHR], 1.27 [95% CI, 1.08-1.49]), large IDWG (aHR, 1.39 [95% CI, 1.23-1.59]), and shortened treatments (aHR, 1.54 [95% CI, 1.12-2.13]) were associated with greater rates of allograft loss, but hyperkalemia was not. Large IDWG (aHR, 1.49 [95% CI, 1.29-1.73]) and shortened treatments (aHR, 1.34 [95% CI, 1.13-1.58]) were associated with mortality, whereas hyperkalemia and hyperphosphatemia were not. Only shortened treatments were associated with an increased risk of acute rejection (adjusted odds ratio, 3.88 [95% CI, 1.98-7.58]). In models limited to the years 2004-2009 that included missed treatments, missed treatments were associated only with mortality. LIMITATIONS: Unmeasured confounding (eg, dietary data); adherence metrics used may have multiple, complex causes. CONCLUSIONS: Plausible measures of dialysis nonadherence have long-term associations with allograft and patient survival. Behavioral metrics were more closely associated with outcomes than laboratory markers were. The implications of nonadherent behaviors for dialysis patients must be carefully considered before patients are excluded from transplantation.

Association Between Pentosan Polysulfate Sodium and Retinal Disorders.

IMPORTANCE: Case series have identified a macular condition hypothesized to be associated with the use of pentosan polysulfate sodium (PPS). Observational studies seeking to quantify this association have yielded equivocal results. OBJECTIVE: To estimate the association between PPS exposure and maculopathy. DESIGN, SETTING, AND PARTICIPANTS: This disproportionality analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System from January 2013 through June 2020. EXPOSURE: Adverse event reports for pentosan polysulfate were selected and compared with adverse event reports associated with drugs taken for the following indications: interstitial cystitis, cystitis, bladder disorder, or bladder pain. MAIN OUTCOME MEASURES: Retinal adverse events were identified using the retinal disorders Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query, which includes conditions associated with retinal damage attributable to blockage of its blood supply, nutritional deficiencies, toxins, and diseases affecting the retina. RESULTS: There were 2775 reports available for analysis in the PPS group (of which 1966 were for women [70.9%]) and 6833 reports in the other drugs group (of which 4036 [59.1%] were for women). The proportion of adverse events for any macular event relative to all other events was elevated for the users of PPS compared with those using other interstitial cystitis and bladder pain drugs (proportionate reporting ratio [PRR], 1.21 [95% CI, 1.01-1.44]). With respect to specific retinal conditions, macular degeneration (20 [0.8%] vs 15 [0.2%]), maculopathy (83 [3.4%] vs 2 [0.03%]), retinal dystrophy (3 [0.1%] vs 0), retinal injury (5 [0.2%] vs 0), and retinal toxicity (3 [0.1%] vs 0) were proportionately more common among users of PPS compared with those using other interstitial cystitis and bladder pain drugs, respectively. CONCLUSIONS AND RELEVANCE: The results of the current study add to the growing evidence that PPS use is associated with an increased risk of maculopathy. Studies that rule out prevalent retinal abnormalities prior to the initiation of PPS would strengthen the current body of literature.