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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.
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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.
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Lesión Renal Aguda , Procedimientos Quirúrgicos Cardíacos , Creatinina , Complicaciones Posoperatorias , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/sangre , Lesión Renal Aguda/epidemiología , Femenino , Masculino , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Anciano , Persona de Mediana Edad , Creatinina/sangre , Factores Sexuales , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/sangre , Factores de Riesgo , Tasa de Filtración GlomerularRESUMEN
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.
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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.
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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.
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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.
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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.
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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.
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Glomeruloesclerosis Focal y Segmentaria , Nefrología , Nefrosis Lipoidea , Síndrome Nefrótico , Humanos , Glomeruloesclerosis Focal y Segmentaria/patología , Nefrosis Lipoidea/diagnóstico , Inhibidor Tisular de Metaloproteinasa-1 , Síndrome Nefrótico/diagnóstico , Factores de Necrosis Tumoral/uso terapéuticoRESUMEN
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 CHA2DS2-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.
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Fibrilación Atrial , Embolia , Fallo Renal Crónico , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Warfarina/efectos adversos , Anticoagulantes/uso terapéutico , Estudios Prospectivos , Resultado del Tratamiento , Hemorragia/epidemiología , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Embolia/prevención & control , Diálisis Renal/efectos adversos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/terapiaRESUMEN
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.
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Enfermedades Renales , Biología de Sistemas , Humanos , Riñón , Michigan , Investigación Biomédica TraslacionalRESUMEN
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 = 58â¯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 58â¯526 patients (median [IQR] age, 66 [56-74] years; 39â¯173 [67%] men; 51â¯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.
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Lesión Renal Aguda/etiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Modelos Estadísticos , Complicaciones Posoperatorias/etiología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Área Bajo la Curva , Humanos , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Valor Predictivo de las Pruebas , Curva ROC , Diálisis Renal , Estudios Retrospectivos , Medición de Riesgo/métodosRESUMEN
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.
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Cirugía Bariátrica , Derivación Gástrica , Hipertensión , Laparoscopía , Obesidad Mórbida , Adulto , Antihipertensivos/uso terapéutico , Gastrectomía , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/cirugía , Obesidad Mórbida/cirugía , Resultado del TratamientoRESUMEN
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 (eGFRcys) and eGFR creatinine-cystatin C (eGFRcr-cys_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.
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Nefrología , Insuficiencia Renal Crónica , Adulto , Creatinina , Tasa de Filtración Glomerular , Promoción de la Salud , Humanos , Riñón , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Estados UnidosRESUMEN
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_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.
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Nefrología , Insuficiencia Renal Crónica , Adulto , Humanos , Estados Unidos , Cistatina C , Tasa de Filtración Glomerular/fisiología , Creatinina , Promoción de la Salud , Insuficiencia Renal Crónica/fisiopatología , Riñón/fisiopatologíaRESUMEN
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.
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For almost two decades, equations that use serum creatinine, age, sex, and race to eGFR have included "race" as Black or non-Black. Given considerable evidence of disparities in health and healthcare 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 one, 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.