Protein N-glycans in Healthy and Sclerotic Glomeruli in Diabetic Kidney Disease.

BACKGROUND: Diabetes is expected to directly impact renal glycosylation, yet to date, there has not been a comprehensive evaluation of alterations in N-glycan composition in the glomeruli of patients with diabetic kidney disease (DKD). METHODS: We used untargeted mass spectrometry imaging to identify N-glycan structures in healthy and sclerotic glomeruli in FFPE sections from needle biopsies of five patients with DKD and three healthy kidney samples. Regional proteomics was performed on glomeruli from additional biopsies from the same patients to compare the abundances of enzymes involved in glycosylation. Secondary analysis of single nuclei transcriptomics (snRNAseq) data was used to inform on transcript levels of glycosylation machinery in different cell types and states. RESULTS: We detected 120 N-glycans, and among them identified twelve of these protein post-translated modifications that were significantly increased in glomeruli. All glomeruli-specific N-glycans contained an N-acetyllactosamine (LacNAc) epitope. Five N-glycan structures were highly discriminant between sclerotic and healthy glomeruli. Sclerotic glomeruli had an additional set of glycans lacking fucose linked to their core, and they did not show tetra-antennary structures that are common in healthy glomeruli. Orthogonal omics analyses revealed lower protein abundance and lower gene expression involved in synthesizing fucosylated and branched N-glycans in sclerotic podocytes. In snRNAseq and regional proteomics analyses, we observed that genes and/or proteins involved in sialylation and LacNAc synthesis were also downregulated in DKD glomeruli, but this alteration remained undetectable by our spatial N-glycomics assay. CONCLUSIONS: Integrative spatial glycomics, proteomics, and transcriptomics revealed protein N-glycosylation characteristic of sclerotic glomeruli in DKD.

Psychosocial characteristics of potential and actual living kidney donors.

The psychosocial assessment is an essential component of the living kidney donor (LKD) evaluation. However, it remains uncertain how specific psychosocial factors impact LKD eligibility. We performed a retrospective chart review of LKD candidates who initiated the evaluation process and who had completed a required, in-person licensed social work (LSW) visit. LSW notes were reviewed for frequency of psychosocial factors that may impact the success of LKD candidate approval by the selection committee. 325 LKD candidates were included in the study: 104 not-approved and 221 approved. Not-approved LKD candidates were more likely to receive a negative family reaction to wanting to donate than approved LKD candidates (8.7% vs 1.4%, p < 0.01). On multivariate analysis, Black race, history of psychiatric illness, highest level of education being high school, and high psychosocial risk score assignment were all associated with a lower odds ratio of being approved. The majority of not-approved LKD candidates were disqualified for medical reasons (N = 76, 73.1%). In conclusion, psychosocial factors impact donation even after LKD candidates make it to an in-person evaluation.

Performance of estimated glomerular filtration rate equations in Black living kidney donor candidates.

INTRODUCTION: New estimated glomerular filtration rate (eGFR) equations using serum creatinine and/or cystatin C have been derived to eliminate adjustment by perceived Black ancestry. We sought to analyze the performance of newer eGFR equations among Black living kidney donor candidates. METHODS: Black candidates (n = 64) who had measured iothalamate GFR between January 2015 and October 2021 were included, and eGFR was calculated using race adjusted (eGFRcr2009 and eGFRcr-cys2012) and race unadjusted (eGFRcys2012, eGFRcr2021, and eGFRcr-cys2021) CKD-EPI equations. Bias and accuracy were calculated. RESULTS: The eGFRcr2021 equation had a negative bias of 9 mL/min/1.73 m2 , while other equations showed a modest positive bias. Accuracy within 10% and 30% was greatest using the eGFRcr-cys2021 equation. With the eGFRcr2021 equation, 9.4% of donors with an mGFR > 80 mL/min/1.73 m2 were misclassified as having an eGFR < 80 mL/min/1.73 m2 . eGFR was also compared among 18 kidney donors at 6-24 months post-donation. Post-donation, the percentage of donors with an eGFR < 60 mL/min/1.73 m2 was 44% using the eGFRcr2021 equation compared to 11% using the eGFRcr-cys2021 equation. CONCLUSION: The CKD-EPICr2021 equation appears to underestimate true GFR in Black living donor candidates. Alternatively, compared to CKD-EPICr2021, the CKD-EPICr-CysC2021 equation appears to perform with less bias and improved accuracy.

Deceased donor kidneys from higher distressed communities are significantly less likely to be utilized for transplantation.

The proportion of kidneys procured for transplantation but not utilized exceeds 20% in the United States. Factors associated with nonutilization are complex, and further understanding of novel causes are critically important. We used the national Scientific Registry of Transplant Recipients data (2010-2022) to evaluate associations of Distressed Community Index (DCI) of deceased donor residence and likelihood of kidney nonutilization (n = 209 413). Deceased donors from higher distressed communities were younger, had an increased history of hypertension and diabetes, were CDC high-risk, and had higher terminal creatinine and donation after brain death. Mechanisms and circumstances of death varied significantly by DCI. The proportion of kidney nonutilization was 19.9%, which increased by DCI quintile (Q1 = 18.1% to Q5 = 21.6%). The adjusted odds ratio of nonutilization from the highest quintile DCI communities was 1.22 (95% CI = 1.16-1.28; reference = lowest DCI), which persisted stratified by donor race. Donors from highly distressed communities were highly variable by the donor service area (range: 1%-51%; median = 21%). There was no increased risk for delayed graft function or death-censored graft loss by donor DCI but modest increased adjusted hazard for overall graft loss (high DCI = 1.05; 95% CI = 1.01-1.10; reference = lowest DCI). Results indicate that donor residential distress is associated with significantly higher rates of donor kidney nonutilization with notable regional variation and minimal impact on recipient outcomes.

Renal Genetics Clinic: 3-Year Experience in the Cleveland Clinic.

Rationale & Objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience. Study Design: Retrospective cohort. Setting & Participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed. Analytical Approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs. Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management. Limitations: Retrospective and single-center study. Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.

Characteristics of Potential and Actual Living Kidney Donors: A Single-center Experience.

BACKGROUND: There are limited data and no national capture of barriers associated with initiating and completing the donation process for potential living kidney donors (LKDs). METHODS: We performed a retrospective analysis of 3001 intake forms completed by prospective LKDs from 2016 to 2019 at a single transplant center. We analyzed data from all potential donors who completed the intake until they became ineligible or withdrew or donation was complete. We used univariate and multivariate models to evaluate independent factors associated with donation at various stages in the donation process. RESULTS: The donation process was deconstructed into 5 steps: intake form, immunologic compatibility testing, clinic evaluation, selection committee review, and donation. The highest percentage of potential donors dropped out after completing the intake form, primarily because of not responding to the follow-up phone call (22.6%). Of 455 potential LKDs that completed immunologic compatibility testing, 36% were ABO or crossmatch incompatible. One-hundred eighty-eight (7.5%) of all LKD applicants reached donation, the majority of whom were White (91.0%) and female (63.8%). CONCLUSIONS: A minority of LKD applicants make it to donation. Our ability to track all potential LKDs from the initial touch point to the transplant center will help us develop interventions to address barriers to a successful donation.

Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients: Results of the CTOT-19 Trial.

BACKGROUND: Ischemia-reperfusion (IR) of a kidney transplant (KTx) upregulates TNF α production that amplifies allograft inflammation and may negatively affect transplant outcomes. METHODS: We tested the effects of blocking TNF peri-KTx via a randomized, double-blind, placebo-controlled, 15-center, phase 2 clinical trial. A total of 225 primary transplant recipients of deceased-donor kidneys (KTx; 38.2% Black/African American, 44% White) were randomized to receive intravenous infliximab (IFX) 3 mg/kg or saline placebo (PLBO) initiated before kidney reperfusion. All patients received rabbit anti-thymocyte globulin induction and maintenance immunosuppression (IS) with tacrolimus, mycophenolate mofetil, and prednisone. The primary end point was the difference between groups in mean 24-month eGFR. RESULTS: There was no difference in the primary end point of 24-month eGFR between IFX (52.45 ml/min per 1.73 m 2 ; 95% CI, 48.38 to 56.52) versus PLBO (57.35 ml/min per 1.73 m 2 ; 95% CI, 53.18 to 61.52; P =0.1). There were no significant differences between groups in rates of delayed graft function, biopsy-proven acute rejection (BPAR), development of de novo donor-specific antibodies, or graft loss/death. Immunosuppression did not differ, and day 7 post-KTx plasma analyses showed approximately ten-fold lower TNF ( P <0.001) in IFX versus PLBO. BK viremia requiring IS change occurred more frequently in IFX (28.9%) versus PLBO (13.4%; P =0.004), with a strong trend toward higher rates of BKV nephropathy in IFX (13.3%) versus PLBO (4.9%; P =0.06). CONCLUSIONS: IFX induction therapy does not benefit recipients of kidney transplants from deceased donors on this IS regimen. Because the intervention unexpectedly increased rates of BK virus infections, our findings underscore the complexities of targeting peritransplant inflammation as a strategy to improve KTx outcomes.Clinical Trial registry name and registration number:clinicaltrials.gov (NCT02495077).

Geographic hot spots of kidney transplant candidates wait-listed post-dialysis.

INTRODUCTION: Preemptive wait-listing of deceased donor kidney transplant (DDKT) candidates before maintenance dialysis increases the likelihood of transplantation and improves outcomes among transplant patients. Previous studies have identified substantial disparities in rates of preemptive listing, but a gap exists in examining geographic sources of disparities, particularly for sub-regional units. Identifying small area hot spots where delayed listing is particularly prevalent may more effectively inform both health policy and regionally appropriate interventions. METHODS: We conducted a retrospective cohort study utilizing 2010-2020 Scientific Registry of Transplant Recipients (SRTR) data for all DDKT candidates to examine overall and race-stratified geospatial hot spots of post-dialysis wait-listing in U.S. zip code tabulation areas (ZCTA). Three geographic clustering methods were utilized to identify robust statistically significant hot spots of post-dialysis wait-listing. RESULTS: Novel sub-regional hot spots were identified in the southeast, southwest, Appalachia, and California, with a majority existing in the southeast. Race-stratified results were more nuanced, but broadly reflected similar patterns. Comparing transplant candidates in hot spots to candidates in non-clusters indicated a strong association between residence in hot spots and high area deprivation (OR: 6.76, 95%CI: 6.52-7.02), indicating that improving access healthcare in these areas may be particularly beneficial. CONCLUSION: Our study identified overall and race-stratified hot spots with low rates of preemptive wait list placement in the U.S., which may be useful for prospective healthcare policy and interventions via targeting of these narrowly defined geographical areas.

Comparative outcomes for over 100 deceased donor kidney transplants from SARS-CoV-2 positive donors: A single-center experience.

Emerging data support the safety of transplantation of extra-pulmonary organs from donors with SARS-CoV-2-detection. Our center offered kidney transplantation (KT) from deceased donors (DD) with SARS-CoV-2 with and without COVID-19 as a cause of death (CoV + COD and CoV+) to consenting candidates. No pre-emptive antiviral therapies were given. We retrospectively compared outcomes to contemporaneous DDKTs with negative SARS-CoV-2 testing (CoVneg). From February 1, 2021 to January 31, 2022, there were 220 adult KTs, including 115 (52%) from 35 CoV+ and 33 CoV + COD donors. Compared to CoVneg and CoV+, CoV + COD were more often DCD (100% vs. 40% and 46%, p < .01) with longer cold ischemia times (25.2 h vs. 22.9 h and 22.2 h, p = .02). At median follow-up of 5.7 months, recipients of CoV+, CoV + COD and CoVneg kidneys had similar rates of delayed graft function (10.3%, 21.8% and 21.9%, p = .16), rejection (5.1%, 0% and 8.5%, p = .07), graft failure (1.7%, 0% and 0%, p = .35), mortality (0.9%, 0% and 3.7%; p = .29), and COVID-19 diagnoses (13.6%, 7.1%, and 15.2%, p = .33). Though follow-up was shorter, CoV + COD was associated with lower but acceptable eGFR on multivariable analysis. KT from DDs at various stages of SARS-CoV-2 infection appears safe and successful. Extended follow-up is required to assess the impact of CoV + COD donors on longer term graft function.

Utilization and outcomes of deceased donor SARS-CoV-2-positive organs for solid organ transplantation in the United States.

Coronavirus disease-19 has had a marked impact on the transplant population and processes of care for transplant centers and organ allocation. Several single-center studies have reported successful utilization of deceased donors with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests. Our aims were to characterize testing, organ utilization, and transplant outcomes with donor SARS-CoV-2 status in the United States. We used Scientific Registry of Transplant Recipients data from March 12, 2020 to August 31, 2021 including a custom file with SARS-CoV-2 testing data. There were 35 347 donor specimen SARS-CoV-2 tests, 77.5% upper respiratory samples, 94.6% polymerase chain reaction tests, and 1.2% SARS-CoV-2-positive tests. Donor age, gender, history of hypertension, and diabetes were similar by SARS-CoV-2 status, while positive SARS-CoV-2 donors were more likely African-American, Hispanic, and donors after cardiac death (p-values <.01). Recipient demographic characteristics were similar by donor SARS CoV-2 status. Adjusted donor kidney discard (odds ratio = 2.08, 95% confidence interval [CI] 1.66-2.61) was higher for SARS-CoV-2-positive donors while donor liver (odds ratio = 0.44, 95% CI 0.33-0.60) and heart recovery (odds ratio = 0.44, 95% CI 0.31-0.63) were significantly reduced. Overall post-transplant graft survival for kidney, liver, and heart recipients was comparable by donor SARS-CoV-2 status. Cumulatively, there has been significantly lower utilization of SARS-CoV-2 donors with no evidence of reduced recipient graft survival with variations in practice over time.

A tool for decision-making in kidney transplant candidates with poor prognosis to receive deceased donor transplantation in the United States.

The primary outcomes for kidney transplant candidates are receipt of deceased or living donor transplant, death or removal from the waiting list. Here, we conducted a retrospective analysis of national Scientific Registry of Transplant Recipients data to evaluate outcomes for 208,717 adult kidney transplant candidates following the 2014 Kidney Allocation System in the United States. Competing risks models were utilized to evaluate Time to Equivalent Risk (TiTER) of deceased donor transplantation (DDTX) and death versus waitlist removal. We also evaluated TiTER based on kidney donor profile index (KDPI) and donor age. For all groups, the cumulative incidence of DDTX was initially higher from time of listing than death or waitlist removal. However, following accrued time on the waiting list, the cumulative incidence of death or waitlist removal exceeded DDTX for certain patient groups, particularly older, diabetic, blood type B and O and shorter pre-listing dialysis time. TiTER for all candidates aged 65-69 averaged 41 months and for 70 and older patients 28 months. Overall, 39.6% of candidates were in risk groups with TiTER under 72 months and 18.5% in groups with TiTER under 24 months. Particularly for older candidates, TiTER for kidneys was substantially shorter for younger donors or lower KDPI. Thus, our findings reveal that a large proportion of wait-listed patients in the United States have poor prognoses to ever undergo DDTX and our data may improve shared decision-making for candidates at time of waitlist placement. Hence, for specific patient groups, TiTER may be a useful tool to disseminate and quantify benefits of accepting relatively high risk donor organs.

Molecular Signatures of Diabetic Kidney Disease Hiding in a Patient with Hypertension-Related Kidney Disease: A Clinical Pathologic Molecular Correlation.

The Kidney Precision Medicine Project (KPMP) seeks to establish a molecular atlas of the kidney in health and disease and improve our understanding of the molecular drivers of CKD and AKI. Herein, we describe the case of a 66-year-old woman with CKD who underwent a protocol KPMP kidney biopsy. Her clinical history included well-controlled diabetes mellitus, hypertension, and proteinuria. The patient's histopathology was consistent with modest hypertension-related kidney injury, without overt diabetic kidney disease. Transcriptomic signatures of the glomerulus, interstitium, and tubular subsegments were obtained from laser microdissected tissue. The molecular signatures that were uncovered revealed evidence of early diabetic kidney disease adaptation and ongoing active tubular injury with enriched pathways related to mesangial cell hypertrophy, glycosaminoglycan biosynthesis, and apoptosis. Molecular evidence of diabetic kidney disease was found across the nephron. Novel molecular assays can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy.

Combining Blood Gene Expression and Cellfree DNA to Diagnose Subclinical Rejection in Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: Subclinical acute rejection is associated with poor outcomes in kidney transplant recipients. As an alternative to surveillance biopsies, noninvasive screening has been established with a blood gene expression profile. Donor-derived cellfree DNA (cfDNA) has been used to detect rejection in patients with allograft dysfunction but not tested extensively in stable patients. We hypothesized that we could complement noninvasive diagnostic performance for subclinical rejection by combining a donor-derived cfDNA and a gene expression profile assay. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a post hoc analysis of simultaneous blood gene expression profile and donor-derived cfDNA assays in 428 samples paired with surveillance biopsies from 208 subjects enrolled in an observational clinical trial (Clinical Trials in Organ Transplantation-08). Assay results were analyzed as binary variables, and then, their continuous scores were combined using logistic regression. The performance of each assay alone and in combination was compared. RESULTS: For diagnosing subclinical rejection, the gene expression profile demonstrated a negative predictive value of 82%, a positive predictive value of 47%, a balanced accuracy of 64%, and an area under the receiver operating curve of 0.75. The donor-derived cfDNA assay showed similar negative predictive value (84%), positive predictive value (56%), balanced accuracy (68%), and area under the receiver operating curve (0.72). When both assays were negative, negative predictive value increased to 88%. When both assays were positive, positive predictive value increased to 81%. Combining assays using multivariable logistic regression, area under the receiver operating curve was 0.81, significantly higher than the gene expression profile (P<0.001) or donor-derived cfDNA alone (P=0.006). Notably, when cases were separated on the basis of rejection type, the gene expression profile was significantly better at detecting cellular rejection (area under the receiver operating curve, 0.80 versus 0.62; P=0.001), whereas the donor-derived cfDNA was significantly better at detecting antibody-mediated rejection (area under the receiver operating curve, 0.84 versus 0.71; P=0.003). CONCLUSIONS: A combination of blood-based biomarkers can improve detection and provide less invasive monitoring for subclinical rejection. In this study, the gene expression profile detected more cellular rejection, whereas donor-derived cfDNA detected more antibody-mediated rejection.

New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race.

BACKGROUND: Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct. METHODS: We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations. RESULTS: In the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m2; 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m2; 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m2; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m2; 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks. CONCLUSIONS: New eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

Early success transplanting kidneys from donors with new SARS-CoV-2 RNA positivity: A report of 10 cases.

Transplantation of solid organs from donors with active SARS-CoV-2 infection has been advised against due to the possibility of disease transmission to the recipient. However, with the exception of lungs, conclusive data for productive infection of transplantable organs do not exist. While such data are awaited, the organ shortage continues to claim thousands of lives each year. In this setting, we put forth a strategy to transplant otherwise healthy extrapulmonary organs from SARS-CoV-2-infected donors. We transplanted 10 kidneys from five deceased donors with new detection of SARS-CoV-2 RNA during donor evaluation in early 2021. Kidney donor profile index ranged from 3% to 56%. All organs had been turned down by multiple other centers. Without clear signs or symptoms, the veracity of timing of SARS-CoV-2 infection could not be confirmed. With 8-16 weeks of follow-up, outcomes for all 10 patients and allografts have been excellent. All have been free of signs or symptoms of donor-derived SARS-CoV-2 infection. Our findings raise important questions about the nature of SARS-CoV-2 RNA detection in potential organ donors and suggest underutilization of exceptionally good extrapulmonary organs with low risk for disease transmission.

Patients with High Priority for Kidney Transplant Who Are Not Given Expedited Placement on the Transplant Waiting List Represent Lost Opportunities.

BACKGROUND: Kidney transplantation is associated with the best outcomes for most patients with ESKD. The national Kidney Allocation System prioritizes patients with Estimated Post-Transplant Survival (EPTS) scores in the top 20% for expedited access to optimal deceased donor kidneys. METHODS: We studied adults aged ≥18 years in the United States Renal Data System with top 20% EPTS scores who had been preemptively waitlisted or initiated dialysis in 2015-2017. We evaluated time to waitlist placement, transplantation, and mortality with unadjusted and multivariable survival models. RESULTS: Of 42,445 patients with top 20% EPTS scores (mean age, 38.0 years; 57% male; 59% White patients, and 31% Black patients), 7922 were preemptively waitlisted. Among 34,523 patients initiating dialysis, the 3-year cumulative waitlist placement incidence was 37%. Numerous factors independently associated with waitlisting included race, income, and having noncommercial insurance. For example, waitlisting was less likely for Black versus White patients, and for patients in the lowest-income neighborhoods versus those in the highest-income neighborhoods. Among patients initiating dialysis, 61% lost their top 20% EPTS status within 30 months versus 18% of patients who were preemptively listed. The 3-year incidence of deceased and living donor transplantation was 5% and 6%, respectively, for patients who initiated dialysis and 26% and 44%, respectively, for patients who were preemptively listed. CONCLUSIONS: Many patients with ESKDqualifying with top 20% EPTS status are not placed on the transplant waiting list in a timely manner, with significant variation on the basis of demographic and social factors. Patients who are preemptively listed are more likely to receive benefits of top 20% EPTS status. Efforts to expedite care for qualifying candidates are needed, and automated transplant referral for patients with the best prognoses should be considered. PODCAST: This article contains a podcast athttps://www.asn-online.org/media/podcast/JASN/2021_07_30_JASN2020081146.mp3.