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.

Renoprotective Effects of Metabolic Surgery Versus GLP1 Receptor Agonists on Progression of Kidney Impairment in Patients with Established Kidney Disease.

OBJECTIVE: To examine the renoprotective effects of metabolic surgery in patients with established chronic kidney disease (CKD). BACKGROUND: The impact of metabolic surgery compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with established CKD has not been fully characterized. METHODS: Patients with obesity (BMI ≥30 kg/m2), type 2 diabetes (T2DM), and baseline estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m² who underwent metabolic bariatric surgery at a large U.S. health system (2010-2017) were compared with nonsurgical patients who continuously received GLP-1RA. The primary end point was CKD progression, defined as decline of eGFR by ≥50% or to <15 mL/min/1.73 m2, initiation of dialysis, or kidney transplant. The secondary end point was the incident kidney failure (eGFR <15 mL/min/1.73 m2, dialysis, or kidney transplant) or all-cause mortality. RESULTS: 425 patients, including 183 patients in the metabolic surgery group and 242 patients in the GLP-1RA group, with a median follow-up of 5.8 years (IQR, 4.4-7.6) were analyzed. The cumulative incidence of the primary end point at 8-years was 21.7% (95% CI, 12.2-30.6) in the surgical group and 45.1% (95% CI, 27.7-58.4) in the nonsurgical group, with an adjusted hazard ratio of 0.40 (95% CI, 0.21-0.76), P=0.006. The cumulative incidence of the secondary composite end point at 8-years was 24.0% (95% CI, 14.1-33.2) in the surgical group and 43.8% (95% CI, 28.1-56.1) in the nonsurgical group, with an adjusted HR of 0.56 (95% CI, 0.31-0.99), P=0.048. CONCLUSIONS: Among patients with T2DM, obesity, and established CKD, metabolic surgery, compared with GLP-1RA, was significantly associated with a 60% lower risk of progression of kidney impairment and a 44% lower risk of kidney failure or death. Metabolic surgery should be considered as a therapeutic option for patients with CKD and obesity.

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.).

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.

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.

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).

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.

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.

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.

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.

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.

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.

Failure to Advance Access to Kidney Transplantation over Two Decades in the United States.

BACKGROUND: Extensive research and policies have been developed to improve access to kidney transplantation among patients with ESKD. Despite this, wide variation in transplant referral rates exists between dialysis facilities. METHODS: To evaluate the longitudinal pattern of access to kidney transplantation over the past two decades, we conducted a retrospective cohort study of adult patients with ESKD initiating ESKD or placed on a transplant waiting list from 1997 to 2016 in the United States Renal Data System. We used cumulative incidence models accounting for competing risks and multivariable Cox models to evaluate time to waiting list placement or transplantation (WLT) from ESKD onset. RESULTS: Among the study population of 1,309,998 adult patients, cumulative 4-year WLT was 29.7%, which was unchanged over five eras. Preemptive WLT (prior to dialysis) increased by era (5.2% in 1997-2000 to 9.8% in 2013-2016), as did 4-year WLT incidence among patients aged 60-70 (13.4% in 1997-2000 to 19.8% in 2013-2016). Four-year WLT incidence diminished among patients aged 18-39 (55.8%-48.8%). Incidence of WLT was substantially lower among patients in lower-income communities, with no improvement over time. Likelihood of WLT after dialysis significantly declined over time (adjusted hazard ratio, 0.80; 95% confidence interval, 0.79 to 0.82) in 2013-2016 relative to 1997-2000. CONCLUSIONS: Despite wide recognition, policy reforms, and extensive research, rates of WLT following ESKD onset did not seem to improve in more than two decades and were consistently reduced among vulnerable populations. Improving access to transplantation may require more substantial interventions.

Rationale and design of the Kidney Precision Medicine Project.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision-medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living-donor kidney biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomic analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for 10 years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.

Long-term kidney transplant graft survival-Making progress when most needed.

Current short-term kidney post-transplant survival rates are excellent, but longer-term outcomes have historically been unchanged. This study used data from the national Scientific Registry of Transplant Recipients (SRTR) and evaluated 1-year and 5-year graft survival and half-lives for kidney transplant recipients in the US. All adult (≥18 years) solitary kidney transplants (n = 331,216) from 1995 to 2017 were included in the analysis. Mean age was 49.4 years (SD +/-13.7), 60% male, and 25% Black. The overall (deceased and living donor) adjusted hazard of graft failure steadily decreased from 0.89 (95%CI: 0.88, 0.91) in era 2000-2004 to 0.46 (95%CI: 0.45, 0.47) for era 2014-2017 (1995-1999 as reference). Improvements in adjusted hazards of graft failure were more favorable for Blacks, diabetics and older recipients. Median survival for deceased donor transplants increased from 8.2 years in era 1995-1999 to an estimated 11.7 years in the most recent era. Living kidney donor transplant median survival increased from 12.1 years in 1995-1999 to an estimated 19.2 years for transplants in 2014-2017. In conclusion, these data show continuous improvement in long-term outcomes with more notable improvement among higher-risk subgroups, suggesting a narrowing in the gap for those disadvantaged after transplantation.

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.

COVID-19 mortality among kidney transplant candidates is strongly associated with social determinants of health.

The COVID-19 pandemic has affected all portions of the global population. However, many factors have been shown to be particularly associated with COVID-19 mortality including demographic characteristics, behavior, comorbidities, and social conditions. Kidney transplant candidates may be particularly vulnerable to COVID-19 as many are dialysis-dependent and have comorbid conditions. We examined factors associated with COVID-19 mortality among kidney transplant candidates from the National Scientific Registry of Transplant Recipients from March 1 to December 1, 2020. We evaluated crude rates and multivariable incident rate ratios (IRR) of COVID-19 mortality. There were 131 659 candidates during the study period with 3534 all-cause deaths and 384 denoted a COVID-19 cause (5.00/1000 person years). Factors associated with increased COVID-19 mortality included increased age, males, higher body mass index, and diabetes. In addition, Blacks (IRR = 1.96, 95% C.I.: 1.43-2.69) and Hispanics (IRR = 3.38, 95% C.I.: 2.46-4.66) had higher COVID-19 mortality relative to Whites. Patients with lower educational attainment, high school or less (IRR = 1.93, 95% C.I.: 1.19-3.12, relative to post-graduate), Medicaid insurance (IRR = 1.73, 95% C.I.: 1.26-2.39, relative to private), residence in most distressed neighborhoods (fifth quintile IRR = 1.93, 95% C.I.: 1.28-2.90, relative to first quintile), and most urban and most rural had higher adjusted rates of COVID-19 mortality. Among kidney transplant candidates in the United States, social determinants of health in addition to demographic and clinical factors are significantly associated with COVID-19 mortality.

Effects of body mass index on kidney transplant outcomes are significantly modified by patient characteristics.

Body mass index (BMI) is a known risk factor associated with kidney transplant outcomes and is incorporated for determining transplant candidate eligibility. However, BMI is a coarse health measure and risks associated with BMI may vary by patient characteristics. We evaluated 296 807 adult (age > 17) solitary kidney transplant recipients from the Scientific Registry of Transplant Recipients (2000-2019). We examined effects of BMI using survival models and tested interactions with recipient characteristics. Overall, BMI demonstrated a "J-Shaped" risk profile with elevated risks for overall graft loss with low BMI and obesity. However, multivariable models indicated interactions between BMI with recipient age, diagnosis, gender, and race/ethnicity. Low BMI was relatively higher risk for older recipients (>60 years), people with type I diabetes, and males and demonstrated no additional risk among younger (18-39) and Hispanic recipients. High BMI was associated with elevated risk for Caucasians and attenuated risk among African Americans and people with type II diabetes. Effects of BMI had variable risks for mortality vs graft loss by recipient characteristics in competing risks models. The association of BMI with posttransplant outcomes is highly variable among kidney transplant recipients. Results are important considerations for personalized care and risk stratification. Findings suggest that transplant contraindications should not be based on absolute BMI thresholds but modified based on patient characteristics.

A New Panel-Estimated GFR, Including ß2-Microglobulin and ß-Trace Protein and Not Including Race, Developed in a Diverse Population.

RATIONALE AND OBJECTIVE: Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFRcr or eGFRcys, respectively), but the inclusion of creatinine in eGFRcr-cys requires specification of a person's race. ß2-Microglobulin (B2M) and ß-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is. STUDY DESIGN: Study of diagnostic test accuracy. SETTING AND PARTICIPANTS: Development in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants. TESTS COMPARED: Panel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-marker panel) with and without age and sex or race. OUTCOMES: GFR measured as the urinary clearance of iothalamate, plasma clearance of iohexol, or plasma clearance of [51Cr]EDTA. RESULTS: Mean measured GFRs were 58.1 and 83.2 mL/min/1.73 m2, and the proportions of Black participants were 38.6% and 24.0%, in the development and validation populations, respectively. In development, addition of age and sex improved the performance of all equations compared with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P < 0.001). The 3-marker panel without race was more accurate than eGFRcys (percentage of estimates greater than 30% different from measured GFR [1 - P30] of 15.6% vs 17.4%; P = 0.01), and the 4-marker panel without race was as accurate as eGFRcr-cys (1 - P30 of 8.6% vs 9.4%; P = 0.2). Results were generally consistent across subgroups. LIMITATIONS: No representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe. CONCLUSIONS: The 4-marker panel eGFR is as accurate as eGFRcr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.

Podocyte density is reduced in kidney allografts with high-risk APOL1 genotypes at transplantation.

Variants in apolipoprotein L1 (APOL1) gene are associated with nondiabetic kidney diseases in black subjects and reduced kidney transplant graft survival. Living and deceased black kidney donors (n = 107) were genotyped for APOL1 variants. To determine whether allografts from high-risk APOL1 donors have reduced podocyte densities contributing to allograft failure, we morphometrically estimated podocyte number, glomerular volume, and podocyte density. We compared allograft loss and eGFR trajectories stratified by APOL1 high-risk and low-risk genotypes. Demographic characteristics were similar in high-risk (n = 16) and low-risk (n = 91) donors. Podocyte density was significantly lower in high-risk than low-risk donors (108 ± 26 vs 127 ± 40 podocytes/106 um3 , P = .03). Kaplan-Meier graft survival (high-risk 61% vs. low-risk 91%, p-value = 0.049) and multivariable Cox models (hazard ratio = 2.6; 95% CI, 0.9-7.8) revealed higher graft loss in recipients of APOL1 high-risk allografts over 48 months. More rapid eGFR decline was seen in recipients of high-risk APOL1 allografts (P < .001). At 60 months, eGFR was 27 vs. 51 mL/min/1.73 min2 in recipients of APOL1 high-risk vs low-risk kidney allografts, respectively. Kidneys from high-risk APOL1 donors had worse outcomes versus low-risk APOL1 genotypes. Lower podocyte density in kidneys from high-risk APOL1 donors may increase susceptibility to CKD from subsequent stresses in both the recipients and donors.