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AimsGenome-wide association studies revealed an association between a locus at 10q11, downstream from CXCL12, and myocardial infarction (MI). However, the relationship among plasma CXCL12, cardiovascular disease (CVD) risk factors, incident MI, and death is unknown.Methods and resultsWe analysed study-entry plasma CXCL12 levels in 3687 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a prospective study of cardiovascular and kidney outcomes in chronic kidney disease (CKD) patients. Mean follow-up was 6 years for incident MI or death. Plasma CXCL12 levels were positively associated with several cardiovascular risk factors (age, hypertension, diabetes, hypercholesterolaemia), lower estimated glomerular filtration rate (eGFR), and higher inflammatory cytokine levels (P < 0.05). In fully adjusted models, higher study-entry CXCL12 was associated with increased odds of prevalent CVD (OR 1.23; 95% confidence interval 1.14, 1.33, P < 0.001) for one standard deviation (SD) increase in CXCL12. Similarly, one SD higher CXCL12 increased the hazard of incident MI (1.26; 1.09,1.45, P < 0.001), death (1.20; 1.09,1.33, P < 0.001), and combined MI/death (1.23; 1.13-1.34, P < 0.001) adjusting for demographic factors, known CVD risk factors, and inflammatory markers and remained significant for MI (1.19; 1.03,1.39, P = 0.01) and the combined MI/death (1.13; 1.03,1.24, P = 0.01) after further controlling for eGFR and urinary albumin:creatinine ratio.ConclusionsIn CKD, higher plasma CXCL12 was associated with CVD risk factors and prevalent CVD as well as the hazard of incident MI and death. Further studies are required to establish if plasma CXCL12 reflect causal actions at the vessel wall and is a tool for genomic and therapeutic trials.

Racial and sexual orientation discrimination may exacerbate the double epidemic of hypertension (HTN) and HIV that affects men of color who have sex with men (MSM). This was a cross-sectional analysis of African American, Asian American, Native Hawaiian, or Pacific Islander (NHPI) MSM living with HIV (PLWH) cohort in Honolulu and Philadelphia. Racial and sexual orientation discrimination, stress, anxiety, and depression were measured with computer-assisted self-interview questionnaires (CASI). We examined the associations between racial and sexual orientation discrimination with hypertension measured both in the office and by 24-h ambulatory blood pressure monitoring (ABPM) using multivariable logistic regression. Sixty participants (60% African American, 18% Asian, and 22% NHPI) completed CASIs and 24-h ABPM. African American participants (80%) reported a higher rate of daily racial discrimination than Asian American (36%) and NHPI participants (17%, p < 0.001). Many participants (51%) reported daily sexual orientation discrimination. Sixty-six percent of participants had HTN by office measurement and 59% had HTN by 24-h ABPM measurement. Participants who experienced racial discrimination had greater odds of having office-measured HTN than those who did not, even after adjustment (Odds Ratio 5.0 (95% Confidence Interval [1.2-20.8], p = 0.03)). This association was not seen with 24-h ABPM. Hypertension was not associated with sexual orientation discrimination. In this cohort, MSM of color PLWH experience significant amounts of discrimination and HTN. Those who experienced racial discrimination had higher in-office blood pressure. This difference was not observed in 24-h APBM and future research is necessary to examine the long-term cardiovascular effects., (© 2024. The Author(s).)

Background: Female sex has been recognized as a risk factor for cardiac surgery associated acute kidney injury (CS-AKI). The current study sought to evaluate whether female sex is a risk factor for CS-AKI, or modifies the association of peri-operative change in serum creatinine with CS-AKI., Methods: Observational study of adult patients undergoing cardiac surgery between 2000 and 2019 in a single U.S. center. The main variable of interest was registered patient sex, identified from electronic medical records. The main outcome was CS-AKI within 2 weeks of surgery., Results: Of 58526 patients, 19353 (33%) were female; 12934 (22%) incurred AKI based on ≥ 0.3 mg/dL or ≥ 50% rise in serum creatinine (any AKI), 3320 (5.7%) had moderate to severe AKI, and 1018 (1.7%) required dialysis within 2 weeks of surgery. Female sex was associated with higher risk for AKI in models that were based on preoperative serum creatinine (OR, 1.35; 95% CI, 1.29-1.42), and lower risk with the use of estimated glomerular filtration, (OR, 0.90; 95% CI, 0.86-0.95). The risk for moderate to severe CS-AKI for a given immediate peri-operative change in serum creatinine was higher in female compared to male patients (p < .0001 and p < .0001 for non-linearity), and the association was modified by pre-operative kidney function (p < .0001 for interaction)., Conclusions: The association of patient sex with CS-AKI and its direction was dependent on the operational definition of pre-operative kidney function, and differential outcome misclassification due to AKI defined by absolute change in serum creatinine., (© 2024. The Author(s).)

Objectives: Examine the: 1) relative role of hemodynamic determinants of acute kidney injury (AKI) obtained in the immediate postcardiac surgery setting compared with established risk factors, 2) their predictive value, and 3) extent mediation via central venous pressure (CVP) and mean arterial pressure (MAP)., Design: Retrospective observational study. The main outcome of the study was moderate to severe AKI, per kidney disease: improving global outcomes, within 14 days of surgery., Setting: U.S. academic medical center., Patients: Adult patients undergoing cardiac surgery between January 2000 and December 2019 ( n = 40,426) in a single U.S.-based medical center. Pulmonary artery catheter measurements were performed at a median of 102 minutes (11, 132) following cardiopulmonary bypass discontinuation., Interventions: None., Measurements and Results: The median age of the cohort was 67 years (58, 75), and 33% were female; 70% had chronic hypertension, 29% had congestive heart failure, and 3% had chronic kidney disease. In a multivariable model, which included comorbidities and traditional intraoperative risk factors, CVP ( p < 0.0001), heart rate ( p < 0.0001), cardiac index ( p < 0.0001), and MAP ( p < 0.0001), were strong predictors of AKI, and superseded factors such as surgery type and cardiopulmonary bypass duration. The cardiac index had a significant interaction with heart rate ( p = 0.026); a faster heart rate had a differentiating effect on the relationship of cardiac index with AKI, where a higher heart rate heightened the risk of AKI primarily in patients with low cardiac output. There was also significant interaction observed between CVP and MAP ( p = 0.009); where the combination of elevated CVP and low MAP had a synergistic effect on AKI incidence., Conclusions: Hemodynamic factors measured within a few hours of surgery showed a strong association with AKI. Furthermore, determinants of kidney perfusion, namely CVP and arterial pressure are interdependent; as are constituents of stroke volume, that is, cardiac output and heart rate., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0111.

Background: The longitudinal response to the COVID-19 vaccines among patients on hemodialysis with and without prior SARS-CoV-2 infection has not been well characterized., Methods: To guide vaccination strategies in patients on hemodialysis, it is critical to characterize the longevity and efficacy of the vaccine; therefore, we conducted a prospective single-center monthly antibody surveillance study between March 2021 and March 2022 to investigate the dynamic humoral response to a series of COVID-19 mRNA vaccines in patients on hemodialysis with and without prior SARS-CoV-2 infection. Monthly quantitative antibody testing was performed using the Beckman Coulter Access SARS-CoV-2 IgG Antibody Test©, which detects IgG antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 spike protein., Results: This cohort of 30 participants (mean age: 61 ± 3 years) predominantly self-identified as African American (97%) and male (53%). Eight participants (27%) had recovered from COVID-19 (recovered) before the vaccine initiation. All participants received two vaccine doses, and 86.6% received a 6-month booster dose. Among patients naïve to COVID-19, the antibody positivity rate (APR) was 55% post-first-dose, 91% post-second-dose, 50% pre-booster at 6 months, 100% post-booster, and 89% at 6 months post-booster. Recovered patients sustained a consistent 100% APR throughout the year. The naïve patients demonstrated lower peak antibody levels post-second-dose than the recovered patients (17.9 ± 3.2 vs. 44.7 ± 5.6, p < 0.001). The peak antibody levels post-booster showed no significant difference between both groups (27.1 ± 3.9 vs. 37.9 ± 8.2, p = 0.20). Two naïve patients contracted COVID-19 during the follow-up period., Conclusions: The patients naïve to COVID-19 exhibited an attenuated and foreshortened antibody response following two doses of the mRNA vaccines compared with the recovered patients, who maintained 100% APR before the booster dose. The 6-month booster dose counteracted declining immunity and stimulated antibody responses in the naïve patients, even in previously non-responsive patients. This observation implies that different booster vaccination strategies might be required for COVID-19-naïve and -recovered patients. Post-vaccination antibody testing may serve as a valuable tool for guiding vaccination strategies.

Rationale & Objective: Most living kidney donors are members of a hemodialysis patient's social network. Network members are divided into core members, those strongly connected to the patient and other members; and peripheral members, those weakly connected to the patient and other members. We identify how many hemodialysis patients' network members offered to become kidney donors, whether these offers were from core or peripheral network members, and whose offers the patients accepted., Study Design: A cross-sectional interviewer-administered hemodialysis patient social network survey., Setting & Participants: Prevalent hemodialysis patients in 2 facilities., Predictors: Network size and constraint, a donation from a peripheral network member., Outcomes: Number of living donor offers, accepting an offer., Analytical Approach: We performed egocentric network analyses for all participants. Poisson regression models evaluated associations between network measures and number of offers. Logistic regression models determined the associations between network factors and accepting a donation offer., Results: The mean age of the 106 participants was 60 years. Forty-five percent were female, and 75% self-identified as Black. Fifty-two percent of participants received at least one living donor offer (range 1-6); 42% of the offers were from peripheral members. Participants with larger networks received more offers (incident rate ratio [IRR], 1.26; 95% CI, 1.12-1.42; P  = 0.001), including networks with more peripheral members (constraint, IRR, 0.97; 95% CI, 0.96-0.98; P  < 0.001). Participants who received a peripheral member offer had 3.6 times greater odds of accepting an offer (OR, 3.56; 95% CI, 1.15-10.8; P  = 0.02) than those who did not receive a peripheral member offer., Limitations: A small sample of only hemodialysis patients., Conclusions: Most participants received at least one living donor offer, often from peripheral network members. Future living donor interventions should focus on both core and peripheral network members., (© 2023 The Authors.)

The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns of injury on kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates of progression and response to therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used to identify molecular pathways which are shared by subgroups of patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Kidney tissue transcriptomic profile-based clustering identified three patient subgroups with shared molecular signatures across independent, North American, European, and African cohorts. One subgroup had significantly greater disease progression (Hazard Ratio 5.2) which persisted after adjusting for diagnosis and clinical measures (Hazard Ratio 3.8). Inclusion in this subgroup was retained even when clustering was limited to those with less than 25% interstitial fibrosis. The molecular profile of this subgroup was largely consistent with tumor necrosis factor (TNF) pathway activation. Two TNF pathway urine markers were identified, tissue inhibitor of metalloproteinases-1 (TIMP-1) and monocyte chemoattractant protein-1 (MCP-1), that could be used to predict an individual's TNF pathway activation score. Kidney organoids and single-nucleus RNA-sequencing of participant kidney biopsies, validated TNF-dependent increases in pathway activation score, transcript and protein levels of TIMP-1 and MCP-1, in resident kidney cells. Thus, molecular profiling identified a subgroup of patients with either MCD or FSGS who shared kidney TNF pathway activation and poor outcomes. A clinical trial testing targeted therapies in patients selected using urinary markers of TNF pathway activation is ongoing., (Copyright © 2022 International Society of Nephrology. All rights reserved.)

End-stage kidney disease (ESKD) affects over 780,000 Americans and is associated with excess morbidity and premature death. Kidney disease health disparities are well-recognized, manifesting as ESKD overburden among racial and ethnic minority populations. Specifically, Black and Hispanic individuals have a 3.4-fold and 1.3-fold greater life risk of developing ESKD than their white counterparts. There is compelling evidence that communities of color have less opportunity to benefit from kidney-specific care throughout the course of their disease, from pre-ESKD, to ESKD home therapies and kidney transplantation. These healthcare inequities have the combined devastating impact of worse outcomes and quality of life for patients and families at a significant financial cost on the healthcare system. In the last three years, across two presidential administrations, bold, broad initiatives have been outlined that, together could lead to significant transformation in kidney health. The Advancing American Kidney Health (AAKH) initiative was established as a national framework to revolutionize kidney care but did not address health equity. More recently, the Advancing Racial Equity executive order was announced, outlining initiatives to promote equity for historically underserved communities. Building from these presidential directives, we outline strategies to address the complex issue of kidney health disparities, focusing on patient awareness, care delivery, scientific advancement, and workforce initiatives. An equity-focused framework will guide policy advancements to reduce the kidney disease burden in susceptible populations and positively impact the health and well-being of all Americans., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-22-566/coif). The series “Endovascular and Surgical Interventions in the End Stage Renal Disease Population” was commissioned by the editorial office without any funding or sponsorship. CAG is a council member of the American Society of Nephrology, speaker to COVID-19 for NIDDK and receives funding support from the National Institutes of Health and NIDDK. The authors have no other conflicts of interest to declare., (2023 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background: There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF)., Methods: The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA 2 DS 2 -VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.5 mg twice daily for patients ≥80 years of age, weight ≤60 kg, or both) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant nonmajor bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1., Results: From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event., Conclusions: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02942407.

Research on kidney diseases is being transformed by the rapid expansion and innovations in omics technologies. The analysis, integration, and interpretation of big data, however, have been an impediment to the growing interest in applying these technologies to understand kidney function and failure. Targeting this urgent need, the University of Michigan O'Brien Kidney Translational Core Center (MKTC) and its Administrative Core established the Applied Systems Biology Core. The Core provides need-based support for the global kidney community centered on enabling incorporation of systems biology approaches by creating web-based, user-friendly analytic and visualization tools, like Nephroseq and Nephrocell, guiding with experimental design, and processing, analysis, and integration of large data sets. The enrichment core supports systems biology education and dissemination through workshops, seminars, and individualized training sessions. Meanwhile, the Pilot and Feasibility Program of the MKTC provides pilot funding to both early-career and established investigators new to the field, to integrate a systems biology approach into their research projects. The relevance and value of the portfolio of training and services offered by MKTC are reflected in the expanding community of young investigators, collaborators, and users accessing resources and engaging in systems biology-based kidney research, thereby motivating MKTC to persevere in its mission to serve the kidney research community by enabling access to state-of-the-art data sets, tools, technologies, expertise, and learning opportunities for transformative basic, translational, and clinical studies that will usher in solutions to improve the lives of people impacted by kidney disease.

Obesity is a leading cause of hypertension (i.e., high blood pressure [BP]). While hypertension can be managed with antihypertensive medication, substantial weight loss can also lower BP, reducing the need for antihypertensive medication. Articles in this review (n = 60) presented data on antihypertensive medication use among adults pre- and postoperatively. Roux-en-Y gastric bypass was the most studied surgical approach followed by Laparoscopic Sleeve Gastrectomy. Antihypertensive medication was discontinued in a large proportion of patients after surgery, and the mean number of antihypertensive medications decreased by approximately one. In almost a third of the studies, over 75% of participants experienced hypertension remission. All articles aside from two reported a decrease in systolic BP, with about 40% reporting a decrease of ≥ 10 mm Hg., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Effective treatment of acute kidney injury (AKI) is predicated on timely diagnosis; however, the lag in the increase in serum creatinine levels after kidney injury may delay therapy initiation., Objective: To determine the derivation and validation of predictive models for AKI after cardiac surgery., Design, Setting, and Participants: Multivariable prediction models were derived based on a retrospective observational cohort of adult patients undergoing cardiac surgery between January 2000 and December 2019 from a US academic medical center (n = 58 526) and subsequently validated on an external cohort from 3 US community hospitals (n = 4734). The date of final follow-up was January 15, 2020., Exposures: Perioperative change in serum creatinine and postoperative blood urea nitrogen, serum sodium, potassium, bicarbonate, and albumin from the first metabolic panel after cardiac surgery., Main Outcomes and Measures: Area under the receiver-operating characteristic curve (AUC) and calibration measures for moderate to severe AKI, per Kidney Disease: Improving Global Outcomes (KDIGO), and AKI requiring dialysis prediction models within 72 hours and 14 days following surgery., Results: In a derivation cohort of 58 526 patients (median [IQR] age, 66 [56-74] years; 39 173 [67%] men; 51 503 [91%] White participants), the rates of moderate to severe AKI and AKIrequiring dialysis were 2674 (4.6%) and 868 (1.48%) within 72 hours and 3156 (5.4%) and 1018 (1.74%) within 14 days after surgery. The median (IQR) interval to first metabolic panel from conclusion of the surgical procedure was 10 (7-12) hours. In the derivation cohort, the metabolic panel-based models had excellent predictive discrimination for moderate to severe AKI within 72 hours (AUC, 0.876 [95% CI, 0.869-0.883]) and 14 days (AUC, 0.854 [95% CI, 0.850-0.861]) after the surgical procedure and for AKI requiring dialysis within 72 hours (AUC, 0.916 [95% CI, 0.907-0.926]) and 14 days (AUC, 0.900 [95% CI, 0.889-0.909]) after the surgical procedure. In the validation cohort of 4734 patients (median [IQR] age, 67 (60-74) years; 3361 [71%] men; 3977 [87%] White participants), the models for moderate to severe AKI after the surgical procedure showed AUCs of 0.860 (95% CI, 0.838-0.882) within 72 hours and 0.842 (95% CI, 0.820-0.865) within 14 days and the models for AKI requiring dialysis and 14 days had an AUC of 0.879 (95% CI, 0.840-0.918) within 72 hours and 0.873 (95% CI, 0.836-0.910) within 14 days after the surgical procedure. Calibration assessed by Spiegelhalter z test showed P >.05 indicating adequate calibration for both validation and derivation models., Conclusions and Relevance: Among patients undergoing cardiac surgery, a prediction model based on perioperative basic metabolic panel laboratory values demonstrated good predictive accuracy for moderate to severe acute kidney injury within 72 hours and 14 days after the surgical procedure. Further research is needed to determine whether use of the risk prediction tool improves clinical outcomes.

Background: In response to a national call for re-evaluation of the use of race in clinical algorithms, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) established a Task Force to reassess inclusion of race in the estimation of glomerular filtration rate (GFR) in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases., Process & Deliberations: The Task Force organized its activities over 10 months in phases to (1) clarify the problem and evidence regarding GFR estimating equations in the United States (described previously in an interim report), and, in this final report, (2) evaluate approaches to address use of race in GFR estimation, and (3) provide recommendations. We identified 26 approaches for the estimation of GFR that did or did not consider race and narrowed our focus, by consensus, to 5 of those approaches. We holistically evaluated each approach considering 6 attributes: assay availability and standardization; implementation; population diversity in equation development; performance compared with measured GFR; consequences to clinical care, population tracking, and research; and patient centeredness. To arrive at a unifying approach to estimate GFR, we integrated information and evidence from many sources in assessing strengths and weaknesses in attributes for each approach, recognizing the number of Black and non-Black adults affected., Recommendations: (1) For US adults (>85% of whom have normal kidney function), we recommend immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the United States because it does not include race in the calculation and reporting, included diversity in its development, is immediately available to all laboratories in the United States, and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals. (2) We recommend national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. If ongoing evidence supports acceptable performance, the CKD-EPI eGFR-cystatin C (eGFR cys ) and eGFR creatinine-cystatin C (eGFR cr-cys&#95;R ) refit without the race variables should be adopted to provide another first-line test, in addition to confirmatory testing. (3) Research on GFR estimation with new endogenous filtration markers and on interventions to eliminate race and ethnic disparities should be encouraged and funded. An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care., Implementation: This unified approach, without specification of race, should be adopted across the United States. High-priority and multistakeholder efforts should implement this solution., (Copyright © 2021 National Kidney Foundation, Inc and the American Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: In response to a national call for re-evaluation of the use of race in clinical algorithms, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) established a Task Force to reassess inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases., Process Deliberations: The Task Force organized its activities over 10 months in phases to ( 1 ) clarify the problem and evidence regarding eGFR equations in the United States (described previously in an interim report), and, in this final report, ( 2 ) evaluate approaches to address use of race in GFR estimation, and ( 3 ) provide recommendations. We identified 26 approaches for the estimation of GFR that did or did not consider race and narrowed our focus, by consensus, to five of those approaches. We holistically evaluated each approach considering six attributes: assay availability and standardization; implementation; population diversity in equation development; performance compared with measured GFR; consequences to clinical care, population tracking, and research; and patient centeredness. To arrive at a unifying approach to estimate GFR, we integrated information and evidence from many sources in assessing strengths and weaknesses in attributes for each approach, recognizing the number of Black and non-Black adults affected., Recommendations: ( 1 ) For US adults (>85% of whom have normal kidney function), we recommend immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the United States because it does not include race in the calculation and reporting, included diversity in its development, is immediately available to all laboratories in the United States, and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals. ( 2 ) We recommend national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm eGFR in adults who are at risk for or have CKD, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. If ongoing evidence supports acceptable performance, the CKD-EPI eGFR-cystatin C (eGFRcys) and eGFR creatinine-cystatin C (eGFRcr-cys&#95;R) refit without the race variables should be adopted to provide another first-line test, in addition to confirmatory testing. ( 3 ) Research on GFR estimation with new endogenous filtration markers and on interventions to eliminate race and ethnic disparities should be encouraged and funded. An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care., Implementation: This unified approach, without specification of race, should be adopted across the United States. High-priority and multistakeholder efforts should implement this solution., (Copyright © 2021 by the American Society of Nephrology and National Kidney Foundation, Inc. All rights reserved.)

Background: The G1 and G2 alleles of apolipoprotein L1 (APOL1) are common in the Black population and associated with increased risk of focal segmental glomerulosclerosis (FSGS). The molecular mechanisms linking APOL1 risk variants with FSGS are not clearly understood, and APOL1's natural absence in laboratory animals makes studying its pathobiology challenging., Methods: In a cohort of 90 Black patients with either FSGS or minimal change disease (MCD) enrolled in the Nephrotic Syndrome Study Network (58% pediatric onset), we used kidney biopsy traits as an intermediate outcome to help illuminate tissue-based consequences of APOL1 risk variants and expression. We tested associations between APOL1 risk alleles or glomerular APOL1 mRNA expression and 83 light- or electron-microscopy traits measuring structural and cellular kidney changes., Results: Under both recessive and dominant models in the FSGS patient subgroup (61%), APOL1 risk variants were significantly correlated (defined as FDR <0.1) with decreased global mesangial hypercellularity, decreased condensation of cytoskeleton, and increased tubular microcysts. No significant correlations were detected in MCD cohort. Independent of risk alleles, glomerular APOL1 expression in FSGS patients was not correlated with morphologic features., Conclusions: While APOL1-associated FSGS is associated with two risk alleles, both one and two risk alleles are associated with cellular/tissue changes in this study of FSGS patients. Our lack of discovery of a large group of tissue differences in FSGS and no significant difference in MCD may be due to the lack of power but also supports investigating whether machine learning methods may more sensitively detect APOL1-associated changes., (© 2021. IPNA.)

For almost 2 decades, equations that use serum creatinine, age, sex, and race to estimate glomerular filtration rate (GFR) have included "race" as Black or non-Black. Given considerable evidence of disparities in health and health care delivery in African American communities, some regard keeping a race term in GFR equations as a practice that differentially influences access to care and kidney transplantation. Others assert that race captures important non-GFR determinants of serum creatinine and its removal from the calculation may perpetuate other disparities. The National Kidney Foundation (NKF) and American Society of Nephrology (ASN) established a task force in 2020 to reassess the inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and subsequent management of patients with, or at risk for, kidney diseases. This interim report details the process, initial assessment of evidence, and values defined regarding the use of race to estimate GFR. We organized activities in phases: (1) clarify the problem and examine evidence, (2) evaluate different approaches to address use of race in GFR estimation, and (3) make recommendations. In phase 1, we constructed statements about the evidence and defined values regarding equity and disparities; race and racism; GFR measurement, estimation, and equation performance; laboratory standardization; and patient perspectives. We also identified several approaches to estimate GFR and a set of attributes to evaluate these approaches. Building on evidence and values, the attributes of alternative approaches to estimate GFR will be evaluated in the next phases and recommendations will be made., (Copyright © 2021 National KidneyFoundation, Inc and the American Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: APOL1 variants contribute to the markedly higher incidence of ESKD in Blacks compared with Whites. Genetic testing for these variants in patients with African ancestry who have nephropathy is uncommon, and no specific treatment or management protocol for APOL1 -associated nephropathy currently exists., Methods: A multidisciplinary, racially diverse group of 14 experts and patient advocates participated in a Delphi consensus process to establish practical guidance for clinicians caring for patients who may have APOL1 -associated nephropathy. Consensus group members took part in three anonymous voting rounds to develop consensus statements relating to the following: ( 1 ) counseling, genotyping, and diagnosis; ( 2 ) disease awareness and education; and ( 3 ) a vision for management of APOL1 -associated nephropathy in a future when treatment is available. A systematic literature search of the MEDLINE and Embase databases was conducted to identify relevant evidence published from January 1, 2009 to July 14, 2020., Results: The consensus group agreed on 55 consensus statements covering such topics as demographic and clinical factors that suggest a patient has APOL1 -associated nephropathy, as well as key considerations for counseling, testing, and diagnosis in current clinical practice. They achieved consensus on the need to increase awareness among key stakeholders of racial health disparities in kidney disease and of APOL1 -associated nephropathy and on features of a successful education program to raise awareness among the patient community. The group also highlighted the unmet need for a specific treatment and agreed on best practice for management of these patients should a treatment become available., Conclusions: A multidisciplinary group of experts and patient advocates defined consensus-based guidance on the care of patients who may have APOL1 -associated nephropathy., (Copyright © 2021 by the American Society of Nephrology.)

Hypertension is a common chronic health condition affecting Filipino Americans. This pilot study examined the feasibility of addressing high rates of hypertension among Filipino Americans through the implementation of a culturally tailored education intervention. Filipino Americans living in the Greater Philadelphia Area were recruited through community-based organizations for participation and were engaged using a community-based participatory research (CBPR) framework. The study included pre- and post-intervention blood pressure measurements, self-reported body mass index, and questionnaires about physical activity and salt intake. The intervention to promote physical activity and reduce salt intake was conducted through two educational sessions and was accompanied by follow-up at 3 months and by the collection of urine samples for 24-h urinary sodium intake biomarker analysis. Following intervention, a non-statistically significant decrease in urine sodium was observed in both the intervention and the control groups. For systolic blood pressure, a reduction of 12.6 mmHg and an increase in 5.3 mmHg was observed in the intervention and control groups, respectively. Diastolic pressure decreased 3.8 mmHg for the intervention group and increased 5.6 mmHg among controls. The culturally tailored education intervention reported here represents a promising tool for blood pressure reduction in high-risk ethnic populations. The methods used were effective for the recruitment and retention of ethnic minorities in a community-based setting.

New treatments, new understanding, and new approaches to translational research are transforming the outlook for patients with kidney diseases. A number of new initiatives dedicated to advancing the field of nephrology-from value-based care to prize competitions-will further improve outcomes of patients with kidney disease. Because of individual nephrologists and kidney organizations in the United States, such as the American Society of Nephrology, the National Kidney Foundation, and the Renal Physicians Association, and international nephrologists and organizations, such as the International Society of Nephrology and the European Renal Association-European Dialysis and Transplant Association, we are beginning to gain traction to invigorate nephrology to meet the pandemic of global kidney diseases. Recognizing the timeliness of this opportunity, the American Society of Nephrology convened a Division Chief Retreat in Dallas, Texas, in June 2019 to address five key issues: ( 1 ) asserting the value of nephrology to the health system; ( 2 ) productivity and compensation; ( 3 ) financial support of faculty's and divisions' educational efforts; ( 4 ) faculty recruitment, retention, diversity, and inclusion; and ( 5 ) ensuring that fellowship programs prepare trainees to provide high-value nephrology care and enhance attraction of trainees to nephrology. Herein, we highlight the outcomes of these discussions and recommendations to the American Society of Nephrology., (Copyright © 2021 by the American Society of Nephrology.)

Purpose: Chronic kidney disease (CKD) patients often develop cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between progression of retinopathy and concurrent incidence of CVD events in participants with CKD., Design: We assessed 1051 out of 1936 participants in the Chronic Renal Insufficiency Cohort Study that were invited to have fundus photographs obtained at two timepoints separated by 3.5 years, on average., Methods: Using standard protocols, presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter calibre were assessed at a retinal image reading centre by trained graders masked to study participants' information. Participants with a self-reported history of CVD were excluded. Incident CVD events were physician adjudicated using medical records and standardised criteria. Kidney function and proteinuria measurements along with CVD risk factors were obtained at study visits., Results: Worsening of retinopathy by two or more steps in the EDTRS retinopathy grading scale was observed in 9.8% of participants, and was associated with increased risk of incidence of any CVD in analysis adjusting for other CVD and CKD risk factors (OR 2.56, 95% CI 1.25 to 5.22, p<0.01). After imputation of missing data, these values were OR=1.66 (0.87 to 3.16), p=0.12., Conclusion: Progression of retinopathy is associated with higher incidence of CVD events, and retinal-vascular pathology may be indicative of macrovascular disease even after adjustment for kidney diseases and CVD risk factors. Assessment of retinal morphology may provide important information when assessing CVD in patients with CKD., Competing Interests: Competing interests: RRT is a consultant for Medtronic, ROX Medical, and receives royalties from UpToDate. ASG has received research funding from Novartis, GlaxoSmithKline and Sanofi. All other coauthors have no financial conflict of interest regarding the contents of this manuscript., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The seating arrangement of in-center hemodialysis is conducive to patients forming a relationship and a social network. We examined how seating in the in-center hemodialysis clinic affected patients forming relationships, whether patients formed relationships with others who have similar transplant behaviors (homophily), and whether these relationships influenced patients (social contagion) to request a living donation from family and friends outside of the clinic., Methods: In this 30-month, prospective cohort study, we observed the relationships of 46 patients on hemodialysis in a hemodialysis clinic. Repeated participant surveys assessed in-center transplant discussions and living-donor requests. A separable temporal exponential random graph model estimated how seating, demographics, in-center transplant discussions, and living-donor requests affected relationship formation via sociality and homophily. We examined whether donation requests spread via social contagion using a susceptibility-infected model., Results: For every seat apart, the odds of participants forming a relationship decreased (OR, 0.74; 95% CI, 0.61 to 0.90; P =0.002). Those who requested a living donation tended to form relationships more than those who did not (sociality, OR, 1.6; 95% CI, 1.02 to 2.6; P =0.04). Participants who discussed transplantation in the center were more likely to form a relationship with another participant who discussed transplantation than with someone who did not discuss transplantation (homophily, OR, 1.9; 95% CI, 1.03 to 3.5; P =0.04). Five of the 36 susceptible participants made a request after forming a relationship with another patient., Conclusions: Participants formed relationships with those they sat next to and had similar transplant behaviors. The observed increase in in-center transplant discussions and living-donation requests by the members of the hemodialysis-clinic social network was not because of social contagion. Instead, participants who requested a living donation were more social, formed more relationships within the clinic, and discussed transplantation with each other as a function of health-behavior homophily., Competing Interests: C.A. Gadegbeku reports receiving research funding from Akebia and Vertex; being a scientific advisor or member of the American Society of Nephrology Council; and having consultancy agreements with Fresenius Kidney Care as medical director. H.M. Gardiner reports receiving honoraria from National Institutes of Health (NIH) and Public Health Management Corporation; and being a governing councilor for the Public Health Education and Health Promotion Section of the American Public Health Association. P.P. Reese reports having ownership interest in various equities, but none which are health related or related to his research; being a coprincipal investigator for investigator-initiated demonstration trials, funded by AbbVie and Merck, which involve transplantation of hepatitis C virus (HCV)–infected organs into recipients who are negative for HCV, followed by HCV treatment; being an associate editor for American Journal of Kidney Diseases; receiving honoraria for talks at academic centers or academic consortia, including Brigham and Women’s Hospital, Brown University, Cedars-Sinai, Health and Human Services, Massachusetts General Hospital, National Kidney Foundation, Northwestern University, and University of Pittsburgh; being a coprincipal investigator for studies of medication adherence (to any statin) funded by CVS Caremark and the NIH; providing volunteer ethics consultation to eGenesis, related to patient selection and education; being a volunteer for United Network for Organ Sharing, including in the role of past chair and current member of the ethics committee; having consultancy agreements with VAL Health – identification of patients with CKD and behavior change strategies; and providing legal consultation for an individual and not a company or institution. All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)

Background: A kidney transplant candidate's social network serves as a pool of potential living donors. Sex and racial differences in network size, network strength, and living donor requests may contribute to disparities in living donor kidney transplantation., Methods: In this multicenter cross-sectional study, we performed an egocentric network analysis via a telephone survey of 132 waitlisted candidates (53% female and 69% Black) to identify demographic and network factors associated with requesting living kidney donations., Results: Female participants made requests to more network members than male participants: incidence rate ratio (IRR) 1.95, 95% confidence interval (CI) [1.24-3.06], P < 0.01. Black participants tended to make more requests than whites (IRR 1.65, 95% CI [0.99-2.73], P = 0.05). The number of requests increased with the size of the network (IRR 1.09, 95% CI [1.02-1.16], P = 0.01); however, network size did not differ by sex or race. Network members who provided greater instrumental support to the candidates were most likely to receive a request: odds ratio 1.39, 95% CI [1.08-1.78], P = 0.01., Conclusions: Transplant candidates' networks vary in size and in the number of requests made to the members. Previously observed racial and sex disparities in living donor kidney transplantation do not appear to be related to network size or to living donation requests, but rather to the network members themselves. Future living donor interventions should focus on the network members and be tailored to their relationship with the candidate.

Background: Non-traditional risk factors like inflammation and oxidative stress play an essential role in the increased cardiovascular disease (CVD) risk prevalent in chronic kidney disease (CKD). Tryptophan catabolism by the kynurenine pathway (KP) is linked to systemic inflammation and CVD in the general and dialysis population. However, the relationship of KP to incident CVD in the CKD population is unknown., Methods: We measured tryptophan metabolites using targeted mass spectrometry in 92 patients with a history of CVD (old CVD); 46 patients with no history of CVD and new CVD during follow-up (no CVD); and 46 patients with no CVD history who developed CVD in the median follow-up period of 2 years (incident CVD)., Results: The three groups are well-matched in age, gender, race, diabetes status and CKD stage, and only differed in total cholesterol and proteinuria. Tryptophan and kynurenine levels significantly decreased in patients with 'Incident CVD' compared with the no CVD or old CVD groups (P = 5.2E-7; P = 0.003 respectively). Kynurenic acid, 3-hydroxykynurenine and kynurenine are all increased with worsening CKD stage (P < 0.05). An increase in tryptophan levels at baseline was associated with 0.32-fold lower odds of incident CVD (P = 0.000014) compared with the no CVD group even after adjustment for classic CVD risk factors. Addition of tryptophan and kynurenine levels to the receiver operating curve constructed from discriminant analysis predicting incident CVD using baseline clinical variables increased the area under the curve from 0.76 to 0.82 (P = 0.04)., Conclusions: In summary, our study demonstrates that low tryptophan levels are associated with incident CVD in CKD., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS)., Methods: FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied., Results: There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (-7.6 points, P = 0.02) and mobility (-4.2, P = 0.02), the number of reported symptoms was associated with worse depression (-2.7 per symptom, P = 0.009) and anxiety (-2.3, P = 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (-2.8 per visit, P < 0.001) and fatigue (-2.4, P = 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (+9.3, P  =  0.03)., Conclusions: PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Importance: Associations between retinopathy and kidney disease have been previously described. The association between the progression of retinopathy and concurrent progression of chronic kidney disease is unknown., Objective: To assess the association between progression of retinopathy and concurrent progression of chronic kidney disease (CKD) among persons with CKD enrolled in a prospective cohort study., Design, Setting, and Participants: A total of 1936 patients with chronic kidney disease enrolled in the multicenter, prospective Chronic Renal Insufficiency Cohort (CRIC) Study were invited to have 2 nonmydriatic fundus photography sessions separated by a mean (SD) of 3.5 (0.5) years. The study was conducted from May 12, 2006, to June 29, 2011. Data analysis was performed from March 16, 2016, to November 17, 2017., Main Outcomes and Measures: Fundus photographs obtained at baseline and then at a follow-up at 3.5 years were reviewed by masked graders for presence and severity of retinopathy, and vessel calibers were assessed using standard protocols. The associations of the changes in retinal features with progression of CKD (50% estimated glomerular filtration rate [eGFR] loss or incident end-stage renal disease, and differences in eGFR slope in the same time period) were assessed with univariable and multivariable logistic regression models., Results: Among 1583 CRIC participants who had baseline fundus photography, had additional follow-up in CRIC, and were at risk for retinopathy progression, 1025 patients (64.8%) had follow-up photography. The odds ratio (OR) for CKD progression associated with worsening of retinopathy in comparison with participants with stable retinopathy was 2.24 (95% CI, 1.28-3.91; P = .005) in univariable analysis among participants with baseline and follow-up photography. In the multivariable analysis, the OR was 1.62 (95% CI, 0.77-3.39; P = .20). The multiple imputation analysis provided similar results., Conclusions and Relevance: Progression of retinopathy appears to be associated with progression of CKD on univariable analysis but not on multivariable analysis suggesting that similar risk factors may be affecting the progression of both retinal and chronic kidney disease.

Physical activity (PA) serves a critical role in maintaining health and preventing chronic diseases, though its influence on high-risk Asian American populations is unclear. The purpose of this study was to determine PA levels among Filipino and Korean Americans at high risk of hypertension and to identify sociodemographic and health-related factors associated with PA levels in these populations. A cross-sectional survey was administered to 137 participants in the Greater Philadelphia Area. Data was collected on PA levels, sociodemographic factors, and health factors. Multinomial logistic regression was conducted to determine predictors associated with low, moderate, and high PA and predictive probabilities were calculated for interaction terms, incorporating ethnicity and blood pressure variables. Overall, 42.33% of participants belonged to the moderately active PA group and 21.90% belonged to the highly active group. In the final multinomial regression model, it was found that having gone to college increased the odds of being in the moderately active PA group (coef. = 1.96, p = 0.034), while having high blood pressure reduced the odds of being in the moderately active PA group (coef. = -2.21, p = 0.022). Lastly, being Korean versus Filipino reduced the odds of being in the highly active category (coef. = -2.89, p = 0.035). Based on predictive probabilities, Koreans and Filipinos with high blood pressure were more likely to belong in the low active PA category (52.31% and 46.33%). These findings highlight the need for culturally relevant PA interventions for promoting and increasing PA levels to prevent and manage hypertension among these populations.

Introduction: Cardiac biomarkers soluble ST2 (sST2) and galectin-3 may reflect cardiac inflammation and fibrosis. It is plausible that these mechanisms may also contribute to the progression of kidney disease. We examined associations of sST2 and galectin-3 with kidney function decline in participants with chronic kidney disease (CKD)., Methods: This was a pooled analysis of 2 longitudinal cohorts of participants with CKD: the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS). We measured circulating concentrations of sST2 and galectin-3 at baseline. Our primary outcome was progression to estimated glomerular filtration rate (eGFR) <15 ml/min per 1.73 m 2 or end-stage renal disease (ESRD). We used competing risk Cox regression models to study the association of sST2 and galectin-3 with CKD progression, adjusting for demographics, kidney function, and comorbidity., Results: Among the 841 participants in the pooled cohort, baseline eGFR was 51 ± 27 ml/min per 1.73 m 2 and median urine albumin-to-creatinine ratio (UACR) was 141 (interquartile range = 15-736) mg/g. Participants with higher sST2 and galectin-3 were more likely to be older, to have heart failure and diabetes, and to have lower eGFR. Adjusting for demographics, kidney function, and comorbidity, every doubling of sST2 was not associated with progression to eGFR <15 ml/min per 1.73 m 2 or ESRD (adjusted hazard ratio 1.02, 95% confidence interval = 0.76-1.38). Every doubling of galectin-3 was significantly associated with a 38% (adjusted hazard ratio = 1.35, 95% confidence interval = 1.01-1.80) increased risk of progression to eGFR <15 ml/min per 1.73 m 2 or ESRD., Conclusion: Higher concentrations of the cardiac biomarker galectin-3 may be associated with progression of CKD, highlighting potential novel mechanisms that may contribute to the progression of kidney disease.

Introduction: The goal of this study was to examine patterns in the likelihood of consent to genetic research among participants in a prospective kidney disease cohort and biobank, and to determine demographic, clinical, and socioeconomic factors linked to consent for ongoing and future genetic research., Methods: The Clinical Phenotyping Resource and Biobank Core (C-PROBE) enrolled 1628 adult and pediatric patients with chronic kidney disease from 2009 to 2017 across 7 sites in the United States. Participants were asked at annual study visits for consent to provide DNA samples for future genetic studies. We compared characteristics of participants by initial consent outcome and consent status at their most recent study visit., Results: Of the C-PROBE participants, 96% consented to genetic studies at their initial study visit. Although African Americans were slightly less likely to consent at baseline (93% vs. 97%, odds ratio = 0.3, P  < 0.02), there were no significant racial or ethnic differences with longitudinal participation. Also, pediatric and adult genetic consent rates were equivalent. The major persistent differences in the likelihood of consent were based on enrollment site, which ranged from 85% to 100% ( P  < 0.0001)., Conclusion: Overall, genetic consent rates for kidney research within the C-PROBE cohort were high. However, differences in consent rates over time and by recruitment site highlight the complexity of genetic consent for biobanking, and potential limitations for generalizability of observations.

Lifestyle modification and health behavior practice among the individuals with cardiometabolic diseases (CMD) are important for secondary prevention and disease control. This study was designed to investigate and compare health behavior practices among Chinese and Filipino Americans with CMD. Three hundred seventy-four Asian Americans (211 Chinese and 163 Filipino) who reside in the greater Philadelphia region and had either CMD or no identified disease were included in the study. Information on smoking, alcohol intake, physical activity, and salt and sweets consumption was collected, as well as demographic and acculturative characteristics. Of the 374 participants, 241 (64.4%) had CMD and 133 (35.6%) had no identified disease. The majority of Chinese and Filipino Americans with CMD failed to meet the dietary and physical activity guidelines, and only a small percentage of them restricted their amount of salt added to food and amount of sweets consumption. Compared to participants with no disease, Chinese participants with CMD were more likely to "never" add salt to food (AOR 4.42 compared to "frequently"). Filipino Americans with CMD were less likely to be those who "never" consume sweets than those who frequently consume sweets (AOR = 0.12). Among the participants with CMD, Chinese participants with CMD were less likely to restrict drinking (AOR 0.11) than Filipinos with CMD. The findings suggest that tailored interventions for Chinese and Filipino Americans with CMD should be developed to enhance their compliance to behavioral guidelines to prevent further disease progression and complications.

Background: The gut microbiota is altered in patients with chronic kidney disease (CKD), and cardiovascular risk increases with progressive CKD. This study examined the potential link between short chain fatty acids (SCFAs), which are produced by the gut microbiota, and cardiovascular outcomes in patients with CKD., Methods: SCFAs were measured using a targeted liquid chromatography-mass spectrometry platform in baseline plasma samples from 214 patients with CKD enrolled in the Clinical Phenotyping Resource and Biobank Core; 81 patients with coronary artery disease (CAD) and 133 without CAD were randomly assigned to training and validation subsets. The primary outcome was a history of CAD and the secondary outcome was a composite history of cardiovascular disease (CVD) at enrollment., Results: We found significantly higher levels of the SCFA valerate among patients with CAD as compared with patients without CAD in the training set (p < 0.001). The valerate concentrations were also significantly higher among subjects with composite outcomes of CVD compared to those without CVD (p = 0.006). These results were subsequently replicated in the validation set. Logistic regression analysis revealed a strong independent association between plasma valerate levels and CVD in both training and validation sets. When valerate was added to the base clinical model comprising of diabetes, hypertension, urinary protein-creatinine ratio, and estimated glomerular filtration rate, it increased the c-statistics for predicting CVD from 0.68 to 0.79 (p = 0.02) in the training set, an observation which was confirmed in the validation set. -Conclusion: This study provides evidence for alterations in gut-microbiota-derived SCFAs with advancing CKD, demonstrates the association of higher plasma valerate levels with pre-existing CVD, and reveals areas for future exploration of cardiovascular risk in patients with CKD., (© 2018 S. Karger AG, Basel.)

Purpose of Review: African Americans are over-burdened with hypertension resulting in excess morbidity and mortality. We highlight the health impact of hypertension in this population, review important observations regarding disease pathogenesis, and outline evidence-based treatment, current treatment guidelines, and management approaches., Recent Findings: Hypertension accounts for 50% of the racial differences in mortality between Blacks and Whites in the USA. Genome-wide association studies have not clearly identified distinct genetic causes for the excess burden in this population as yet. Pathophysiology is complex likely involving interaction of genetic, biological, and social factors prevalent among African Americans. Non-pharmacologic and pharmacologic therapy is required and specific treatment guidelines for this population are varied. Combination therapy is most often necessary and single-pill formulations are most successful in achieving BP targets. Racial health disparities related to hypertension in African Americans are a serious public health concern that warrants greater attention. Multi-disciplinary research to understand the inter-relationship between biological and social factors is needed to guide successful treatments. Comprehensive care strategies are required to successfully address and eliminate the hypertension burden.

Hypertension and blood pressure variability (BPV; SD and average real variability) in primary proteinuric glomerulopathies are not well described. Data were from 433 participants in the NEPTUNE (Nephrotic Syndrome Study Network). Hypertensive BP status was defined as previous history of hypertension or BP ≥140/90 mm Hg for adults/≥95th percentile for children at baseline. BPV was measured in participants with ≥3 visits in the first year. Two-hundred ninety-six adults (43 years [interquartile range, 32-57.8 years], 61.5% male) and 147 children (11 years [interquartile range, 5-14 years], 57.8% male) were evaluated. At baseline, 64.8% of adults and 46.9% of children were hypertensive. Histological diagnosis was associated with hypertensive status in adults ( P =0.036). In adults, hypertensive status was associated with lower hazard of complete remission (hazard ratio, 0.36; 95% confidence interval, 0.19-0.68) and greater hazard of achieving the composite end point (end-stage renal disease or estimated glomerular filtration rate decline >40%; hazard ratio, 4.1; 95% confidence interval, 1.4-12). Greater systolic and diastolic SD and average real variability were also associated with greater hazard of reaching the composite end point in adults (all P <0.01). In children, greater BPV was an independent predictor of composite end point (determined by systolic SD and average real variability) and complete remission (determined by systolic and diastolic average real variability; all P <0.05). Hypertensive status was common among adults and children enrolled in NEPTUNE. Differences in hypertensive status prevalence, BPV, and treatment were found by age and histological diagnosis. In addition, hypertensive status and greater BPV were associated with poorer clinical outcomes., (© 2017 American Heart Association, Inc.)

Despite that Filipino Americans represent an important target group for hypertension, health behaviors associated with hypertension in this population have not been well studied. Two hundred Filipino Americans from eight community-based organizations completed the study. Information was collected to determine whether modifiable behavioral factors, as well as acculturation and demographic characteristics, were associated with hypertension status in Filipino Americans. Approximately 67% of Filipino Americans were hypertensive. Logistic regression analysis showed that adding salt, physical inactivity, and old age were significantly associated with hypertension status after controlling for other covariates. The present study confirmed a high rate of hypertension among Filipino Americans and demonstrates the association of hypertension status with behavioral factors. These findings highlight the need for targeted interventions to prevent and manage hypertension in this high-risk community by facilitating health behaviors, particularly, salt reduction and physical activity.

Growth differentiation factor-15 (GDF-15) is a member of the TGF- β cytokine superfamily that is widely expressed and may be induced in response to tissue injury. Elevations in GDF-15 may identify a novel pathway involved in loss of kidney function among patients with CKD. Among participants in the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS), we tested whether kidney tissue expression of GDF15 mRNA correlates with circulating levels of GDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function. In matching samples of 24 patients with CKD from the C-PROBE study, circulating GDF-15 levels significantly correlated with intrarenal GDF15 transcript levels ( r =0.54, P =0.01). Among the 224 C-PROBE and 297 SKS participants, 72 (32.1%) and 94 (32.0%) patients, respectively, reached a composite end point of 30% decline in eGFR or progression to ESRD over a median of 1.8 and 2.0 years of follow up, respectively. In multivariable models, after adjusting for potential confounders, every doubling of GDF-15 level associated with a 72% higher (95% confidence interval, 1.21 to 4.45; P =0.003) and 65% higher (95% confidence interval, 1.08 to 2.50; P =0.02) risk of progression of kidney disease in C-PROBE and SKS participants, respectively. These results show that circulating GDF-15 levels strongly correlated with intrarenal expression of GDF15 and significantly associated with increased risk of CKD progression in two independent cohorts. Circulating GDF-15 may be a marker for intrarenal GDF15 -related signaling pathways associated with CKD and CKD progression., (Copyright © 2017 by the American Society of Nephrology.)

Background: The role of myeloperoxidase in chronic kidney disease (CKD) and its association with coronary artery disease (CAD) is controversial. In this study, we compared myeloperoxidase and protein-bound 3-chlorotyrosine (ClY) levels in subjects with varying degrees of CKD and tested their associations with CAD., Methods: From Clinical Phenotyping Resource and Biobank Core, 111 patients were selected from CKD stages 1 to 5. Plasma myeloperoxidase level was measured using enzyme-linked-immunosorbent assay. Plasma protein-bound 3-ClY, a specific product of hypochlorous acid generated by myeloperoxidase was measured by liquid chromatography mass spectrometry., Results: We selected 29, 20, 24, 22, and 16 patients from stages 1 to 5 CKD, respectively. In a sex-adjusted general linear model, mean ± SD of myeloperoxidase levels decreased from 18.1 ± 12.3 pmol in stage 1 to 10.9 ± 4.7 pmol in stage 5 (p = 0.011). In patients with and without CAD, the levels were 19.1 ± 10.1 and 14.8 ± 8.7 pmol (p = 0.036). There was an increase in 3-ClY mean from 0.81 ± 0.36 mmol/mol-tyrosine in stage 1 to 1.42 ± 0.41 mmol/mol-tyrosine in stage 5 (p < 0.001). The mean 3-ClY levels in patients with and without CAD were 1.25 ± 0.44 and 1.04 ± 0.42 mmol/mol-tyrosine (p = 0.023), respectively. C-statistic of ClY when added to myeloperoxidase level to predict CKD stage 5 was 0.86, compared to 0.79 for the myeloperoxidase level alone (p = 0.0097)., Conclusion: The myeloperoxidase levels decrease from stages 1 to 5, whereas activity increases. In contrast, both myeloperoxidase and ClY levels rise in the presence of CAD at various stages of CKD. Measuring both plasma myeloperoxidase and 3-CLY levels provide added value to determine the burden of myeloperoxidase-mediated oxidative stress., (© 2017 S. Karger AG, Basel.)

To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58.6 years, diabetes duration 13.1 years, estimated glomerular filtration rate of 88.2 ml/min/1.73 m(2), and a median spot urine albumin to creatinine ratio of 10.0 mg/g. In additive genetic models adjusting for age, sex, ancestry, scanner, intracranial volume, body mass index, hemoglobin A1c, statins, nephropathy, smoking, hypertension, and cardiovascular disease, APOL1 renal-risk-variants were positively associated with gray matter volume (β = 3.4 × 10(-3)) and negatively associated with white matter lesion volume (β = -0.303) (an indicator of cerebral small vessel disease) and cerebrospinal fluid volume (β= -30707) (all significant), but not with white matter volume or cognitive function. Significant associations corresponding to adjusted effect sizes (β/SE) were observed with gray matter volume (0.16) and white matter lesion volume (-0.208), but not with cerebrospinal fluid volume (-0.251). Meta-analysis results with SPRINT Memory and Cognition in Decreased Hypertension (MIND) participants who had cerebral MRI were confirmatory. Thus, APOL1 renal-risk-variants are associated with larger gray matter volume and lower white matter lesion volume suggesting lower intracranial small vessel disease., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: This analysis from the Nephrotic Syndrome Study Network (NEPTUNE) assessed the phenotypic and pathology characteristics of proteinuric patients undergoing kidney biopsy and defined the frequency and factors associated with complete proteinuria remission (CRever)., Design, Setting, Participants, & Measurements: We enrolled adults and children with proteinuria ≥0.5 g/d at the time of first clinically indicated renal biopsy at 21 sites in North America from April 2010 to June 2014 into a prospective cohort study. NEPTUNE central pathologists assigned participants to minimal-change disease (MCD), FSGS, membranous nephropathy, or other glomerulopathy cohorts. Outcome measures for this analysis were (1) CRever with urine protein-to-creatinine ratio (UPC) <0.3 g/g with preserved native kidney function and (2) ESRD. Continuous variables are reported as median and interquartile range (IQR; 25th, 75th percentile). Cox proportional hazards modeling was used to assess factors associated with CRever., Results: We enrolled 441 patients: 116 (27%) had MCD, 142 (32%) had FSGS, 66 (15%) had membranous nephropathy, and 117 (27%) had other glomerulopathy. The baseline UPC was 4.1 g/g (IQR, 1.9, 7.7) and the eGFR was 81 ml/min per 1.73 m(2) (IQR, 50, 105). Median duration of observation was 19 months (IQR, 11, 30). CRever occurred in 46% of patients, and 4.6% progressed to ESRD. Multivariate analysis demonstrated that higher prebiopsy proteinuria (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.5) and pathology diagnosis (FSGS versus MCD; hazard ratio, 0.2; 95% confidence interval, 0.1 to 0.5) were inversely associated with CRever. The effect of immunosuppressive therapy on remission varied by pathology diagnosis., Conclusions: In NEPTUNE, the high frequency of other pathology in proteinuric patients affirms the value of the diagnostic kidney biopsy. Clinical factors, including level of proteinuria before biopsy, pathology diagnosis, and immunosuppression, are associated with complete remission., (Copyright © 2016 by the American Society of Nephrology.)

Chronic kidney disease (CKD) affects 8 to 16% people worldwide, with an increasing incidence and prevalence of end-stage kidney disease (ESKD). The effective management of CKD is confounded by the inability to identify patients at high risk of progression while in early stages of CKD. To address this challenge, a renal biopsy transcriptome-driven approach was applied to develop noninvasive prognostic biomarkers for CKD progression. Expression of intrarenal transcripts was correlated with the baseline estimated glomerular filtration rate (eGFR) in 261 patients. Proteins encoded by eGFR-associated transcripts were tested in urine for association with renal tissue injury and baseline eGFR. The ability to predict CKD progression, defined as the composite of ESKD or 40% reduction of baseline eGFR, was then determined in three independent CKD cohorts. A panel of intrarenal transcripts, including epidermal growth factor (EGF), a tubule-specific protein critical for cell differentiation and regeneration, predicted eGFR. The amount of EGF protein in urine (uEGF) showed significant correlation (P < 0.001) with intrarenal EGF mRNA, interstitial fibrosis/tubular atrophy, eGFR, and rate of eGFR loss. Prediction of the composite renal end point by age, gender, eGFR, and albuminuria was significantly (P < 0.001) improved by addition of uEGF, with an increase of the C-statistic from 0.75 to 0.87. Outcome predictions were replicated in two independent CKD cohorts. Our approach identified uEGF as an independent risk predictor of CKD progression. Addition of uEGF to standard clinical parameters improved the prediction of disease events in diverse CKD populations with a wide spectrum of causes and stages., (Copyright © 2015, American Association for the Advancement of Science.)

Patients with chronic kidney disease (CKD) experience other diseases such as cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess whether retinopathy predicts future CVD events in a subgroup of the participants of the Chronic Renal Insufficiency Cohort (CRIC) study. In this ancillary investigation, 2,605 participants of the CRIC study were invited to participate, and nonmydriatic fundus photographs were obtained in 1,936 subjects. Using standard protocols, presence and severity of retinopathy (diabetic, hypertensive, or other) and vessel diameter caliber were assessed at a central photograph reading center by trained graders masked to study participant's information. Patients with a self-reported history of cardiovascular disease were excluded. Incident CVD events were adjudicated using medical records. Kidney function measurements, traditional and nontraditional risk factors, for CVD were obtained. Presence and severity of retinopathy were associated with increased risk of development of any CVD in this population of CKD patients, and these associations persisted after adjustment for traditional risk factors for CVD. We also found a direct relation between increased venular diameter and risk of development of CVD; however, the relation was not statistically significant after adjustment for traditional risk factors. In conclusion, the presence of retinopathy was associated with future CVD events, suggesting that retinovascular pathology may be indicative of macrovascular disease even after adjustment for renal dysfunction and traditional CVD risk factors. Assessment of retinal morphology may be valuable in assessing risk of CVD in patients with CKD, both clinically and in research settings., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Chronic inflammation is increased in patients with chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality. Specific immune mechanisms and pathways that drive and maintain chronic inflammation in CKD are not well described. The TAM ligands (Gas6 and protein S) and receptors (Axl and Mer) have been recently recognized as playing a prominent role in immune regulation. The receptors exist in both soluble and cell-bound forms; the soluble receptors (sAxl and sMer) are believed to compete with the bound receptors and thus inhibit their function. In this study, we determined the expression of cell-bound and soluble TAM proteins in patients with CKD. CKD patients had significantly lower expression of Mer in monocytes, yet increased expression of soluble TAM receptors sAxl and sMer in plasma compared to controls. The metalloproteinase ADAM 17, responsible for cleavage of Mer to its soluble form, was increased in patient monocytes. Elevated levels of soluble TAM receptors were more evident in patients with progressive renal failure. These observations suggest that functional deficiency of TAM receptor-mediated regulation of inflammation may contribute to chronic inflammation in patients with CKD., (Copyright © 2015 Elsevier Inc. All rights reserved.)