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Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.
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Ilhas de CpG , Metilação de DNA , Taxa de Filtração Glomerular , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Negro ou Afro-Americano/genética , Idoso , Estudo de Associação Genômica Ampla , Epigênese Genética , Adulto , Predisposição Genética para DoençaRESUMO
Objectives: To describe the social drivers of health and health status of Native Hawaiian and Pacific Islander (NHPI) youth in the US. Methods: This is a cross-sectional analysis of the 2014 NHPI National Health Interview Survey (NHIS) which surveyed about 3,000 NHPI households, including 1,428 NHPI youth (884 0-12 yo, 421 13-17 yo, and 123 18-21 yo). We described domains of social drivers of health (SDoH), health conditions, and associations of income and food insecurity with body mass index (BMI) for NHPI youth. Results: NHPI youth come from households with a wide range in income. Approximately 20% of the cohort were food insecure. Among 18-21 yo, 10% report chronic medical conditions (5% with prediabetes). 33% of 13-17 yo and 52% of 18-21 yo were overweight/ obese. For 13-17 yo, lower income was associated with higher BMI. There was no association between food insecurity and BMI for any age group. Conclusions: Overweight/ obesity are highly prevalent among NHPI youth which is concerning for development of diabetes, hypertension, cardiovascular and kidney disease. Health efforts should focus on SDoH, obesity prevention and management for NHPI youth.
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CONTEXT: Though discrimination in healthcare settings is increasingly recognized, the discriminatory experiences of patients with serious illness has not been well studied. OBJECTIVES: Describe racial differences in patient-reported experiences with discrimination in the healthcare setting and examine its association with mistrust. METHODS: We used surveys containing patient-reported frequency of discrimination using the Discrimination in Medical Setting (DMS) and Microaggressions in Health Care Settings (MHCS) scales, mistrust using the Group Based Medical Mistrust (GBMM) scale, and patient characteristics including patient-reported race, income, wealth, insurance status, and educational attainment. Univariable and multivariable linear regression models as well as risk ratios were used to examine associations between patient characteristics including self-reported race, and DMS, MHCS, and GBMM scores. RESULTS: In 174 participants with serious illness, racially minoritized patients were more likely to report experiencing discrimination and microaggressions. In adjusted analyses, DMS scores were associated with elements of class and not with race. Black, Native American/Alaskan Native (NA/AN), and multiracial participants had higher MHCS scores compared to White participants with similar levels of income and education. Higher income was associated with lower GBMM scores in participants with similar DMS or MHCS scores, but Black and NA/AN participants still reported higher levels of mistrust. CONCLUSION: In this cross-sectional study of patients with serious illness, discriminatory experiences were associated with worse mistrust in the medical system, particularly for Black and NA/AN participants. These findings suggest that race-conscious approaches are needed to address discrimination and mistrust in marginalized patients with serious illness and their families.
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Negro ou Afro-Americano , Confiança , Humanos , Estudos Transversais , Atenção à Saúde , Grupos Raciais , Estados Unidos , Brancos , Indígena Americano ou Nativo do AlascaRESUMO
Importance: Uncertainty remains among clinicians regarding processes to address and resolve conflict around anti-Black racism. Objective: To elicit clinicians' perceptions of their role in addressing concerns about anti-Black racism among Black patients with serious illness as well as their families. Design, Setting, and Participants: In this qualitative study, one-on-one semistructured interviews were conducted with 21 physicians at an academic county hospital between August 1 and October 31, 2022. Participants were provided clinical scenarios where anti-Black racism was a concern of a patient with serious illness. Participants were asked open-ended questions about initial impressions, prior similar experiences, potential strategies to address patients' concerns, and additional resources to support these conversations. A framework based on restorative justice was used to guide qualitative analyses. Main Outcomes and Measures: Perspectives on addressing anti-Black racism as described by physicians. Results: A total of 21 medical subspecialists (mean [SD] age, 44.2 [7.8] years) participated in the study. Most physicians were women (14 [66.7%]), 4 were Asian (19.0%), 3 were Black (14.3%), and 14 were White (66.7%). Participants identified practices that are normalized in clinical settings that may perpetuate and exacerbate perceptions of anti-Black racism. Using provided scenarios and personal experiences, participants were able to describe how Black patients are harmed as a result of these practices. Last, participants identified strategies and resources for addressing Black patients' concerns and facilitating conflict resolution, but they stopped short of promoting personal or team accountability for anti-Black racism. Conclusions and Relevance: In this qualitative study, physicians identified resources, skills, and processes that partially aligned with a restorative justice framework to address anti-Black racism and facilitate conflict resolution, but did not provide steps for actualizing accountability. Restorative justice and similar processes may provide space within a mediated setting for clinicians to repair harm, provide accountability, and facilitate racial healing.
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Médicos , Racismo , Adulto , Feminino , Humanos , Masculino , População Negra , Justiça Social , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Racism negatively affects clinical outcomes in Black patients, but uncertainty remains among physicians regarding how to address interpersonal anti-Black racism incidences involving them to facilitate racial healing and promote accountability. OBJECTIVE: Elicit physician perspectives on addressing concerns from Black patients about interpersonal racism involving them or their team. PARTICIPANTS: Twenty-one physician subspecialists at an urban academic medical center. APPROACH: We conducted one-on-one semi-structured interviews to help inform the development of a clinician-facing component of a program to address the distress of racism experienced by Black patients with serious illness. We asked clinicians to describe experiences discussing racism with patients and identify additional resources to support these conversations. MAIN MEASURES: Physician perspectives, including barriers and facilitators, to promote racial healing and clinician accountability when discussing clinician-perpetuated interpersonal racism with Black patients. KEY RESULTS: Of the 21 participating physicians, 67% were women with a mean age of 44.2 years and mean of 10.8 years of experience as an attending physician. Four identified as Asian, three identified as Black, and 14 identified as White. Participants largely felt unprepared to discuss racism with their patients, especially if the harm was caused by them or their team. Participants felt patients should be given tools to discuss concerns about racism with their clinicians, but worried about adding additional burdens to Black patients to call out racism. Participants believed programs and processes with both patient- and clinicians-facing components had the potential to empower patients while providing resources and tools for clinicians to engage in these highly sensitive discussions without perpetuating more harm. CONCLUSIONS: Addressing and improving communication about interpersonal racism in clinical settings are challenging. Dual-facing programs involving patients and clinicians may help provide additional resources to address experiences of interpersonal racism and hold clinicians accountable.
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Importance: Black patients with serious illness experience higher-intensity care at the end of life. Little research has used critical, race-conscious approaches to examine factors associated with these outcomes. Objective: To investigate the lived experiences of Black patients with serious illness and how various factors may be associated with patient-clinician communication and medical decision-making. Design, Setting, and Participants: In this qualitative study, one-on-one, semistructured interviews were conducted with 25 Black patients with serious illness hospitalized at an urban academic medical center in Washington State between January 2021 and February 2023. Patients were asked to discuss experiences with racism, how those experiences affected the way they communicated with clinicians, and how racism impacted medical decision-making. Public Health Critical Race Praxis was used as framework and process. Main Outcomes and Measures: The experience and of racism and its association, as described by Black patients who had serious illness, with patient-clinician communication and medical decision-making within a racialized health care setting. Results: A total of 25 Black patients (mean [SD] age, 62.0 [10.3] years; 20 males [80.0%]) with serious illness were interviewed. Participants had substantial socioeconomic disadvantage, with low levels of wealth (10 patients with 0 assets [40.0%]), income (annual income <$25â¯000 among 19 of 24 patients with income data [79.2%]), educational attainment (mean [SD] 13.4 [2.7] years of schooling), and health literacy (mean [SD] score in the Rapid Estimate of Adult Literacy in Medicine-Short Form, 5.8 [2.0]). Participants reported high levels of medical mistrust and high frequency of discrimination and microaggressions experienced in health care settings. Participants reported epistemic injustice as the most common manifestation of racism: silencing of their own knowledge and lived experiences about their bodies and illness by health care workers. Participants reported that these experiences made them feel isolated and devalued, especially if they had intersecting, marginalized identities, such as being underinsured or unhoused. These experiences were associated with exacerbation of existing medical mistrust and poor patient-clinician communication. Participants described various mechanisms of self-advocacy and medical decision-making based on prior experiences with mistreatment from health care workers and medical trauma. Conclusions and Relevance: This study found that Black patients' experiences with racism, specifically epistemic injustice, were associated with their perspectives on medical care and decision-making during serious illness and end of life. These findings suggest that race-conscious, intersectional approaches may be needed to improve patient-clinician communication and support Black patients with serious illness to alleviate the distress and trauma of racism as these patients near the end of life.
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Letramento em Saúde , Relações Médico-Paciente , Racismo , Humanos , Masculino , Pessoa de Meia-Idade , Morte , Confiança , Negro ou Afro-Americano , Feminino , IdosoRESUMO
Insurance type, a marker of socioeconomic status, has been associated with poor access to kidney transplant (KT) and worse KT outcomes before the implementation of the Affordable Care Act (ACA) and the revised Kidney Allocation System (KAS). In this study, we assessed if insurance type remained a risk marker for worse waitlist and transplant outcomes after ACA and KAS. Methods: Using Scientific Registry of Transplant Recipients data, we assessed insurance type of waitlisted candidates pre- (2008-2014) versus post- (2014-2021) KAS/ACA using chi-square tests. Next, we performed a competing risk analysis to study the effect of private versus public (Medicare, Medicaid, or government-sponsored) insurance on waitlist outcomes and a Cox survival analysis to study posttransplant outcomes while controlling for candidate, and recipient and donor variables, respectively. Results: The proportion of overall KT candidates insured by Medicaid increased from pre-KAS/ACA to post-KAS/ACA (from 12 667 [7.3%] to 21 768 [8.8%], P < 0.0001). However, KT candidates with public insurance were more likely to have died or become too sick for KT (subdistribution hazard ratio [SHR] = 1.33, confidence interval [CI], 1.30-1.36) or to receive a deceased donor KT (SHR = 1.57, CI, 1.54-1.60) but less likely to receive a living donor KT (SHR = 0.87, CI, 0.85-0.89). Post-KT, KT recipients with public insurance had greater risk of mortality (relative risks = 1.22, CI, 1.15-1.31) and allograft failure (relative risks = 1.10, CI, 1.03-1.29). Conclusions: Although the implementation of ACA marginally increased the proportion of waitlisted candidates with Medicaid, publicly insured KT candidates remained at greater risk of being removed from the waitlist, had lower probability of living donor kidney transplantation, and had greater probability of dying post-KT and allograft failure. Concerted efforts to address factors contributing to these inequities in future studies are needed, with the goal of achieving equity in KT for all.
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Diagnostic and therapeutic advances during the past decades have substantially improved health outcomes for patients with acute coronary syndrome. Both age-related physiological changes and accumulated cardiovascular risk factors increase the susceptibility to acute coronary syndrome over a lifetime. Compared with younger patients, outcomes for acute coronary syndrome in the large and growing demographic of older adults are relatively worse. Increased atherosclerotic plaque burden and complexity of anatomic disease, compounded by age-related cardiovascular and noncardiovascular comorbid conditions, contribute to the worse prognosis observed in older individuals. Geriatric syndromes, including frailty, multimorbidity, impaired cognitive and physical function, polypharmacy, and other complexities of care, can undermine the therapeutic efficacy of guidelines-based treatments and the resiliency of older adults to survive and recover, as well. In this American Heart Association scientific statement, we (1) review age-related physiological changes that predispose to acute coronary syndrome and management complexity; (2) describe the influence of commonly encountered geriatric syndromes on cardiovascular disease outcomes; and (3) recommend age-appropriate and guideline-concordant revascularization and acute coronary syndrome management strategies, including transitions of care, the use of cardiac rehabilitation, palliative care services, and holistic approaches. The primacy of individualized risk assessment and patient-centered care decision-making is highlighted throughout.
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Síndrome Coronariana Aguda , Estados Unidos/epidemiologia , Humanos , Idoso , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/terapia , Fatores de Risco , American Heart Association , Medição de Risco , PrognósticoRESUMO
Introduction: Secretion of solutes by the proximal tubules represents an intrinsic kidney function not directly reflected by the glomerular filtration rate (GFR). The early loss of secretory clearance may reflect unrecognized kidney dysfunction, portending future disease progression. Methods: We designed a nested case-control study within the Jackson Heart Study (JHS), a prospective study of African American adults in Mississippi, to associate baseline differences in proximal tubular secretion of 5 endogenously produced solutes with future estimated glomerular rate (eGFR) decline. We matched 127 pairs by creatinine-eGFR, age, diabetes, and sex among the patients who provided a 24-hour urine collection; cases had a ≥25% decline in eGFR compared to <10% in controls over 10 years of follow-up. We measured baseline plasma and urine concentrations of secretory solutes using liquid chromatography-mass spectrometry to determine the odds ratio of kidney disease progression. Results: Mean age was 60 years; 76% were women; 30% had diabetes; mean baseline eGFR was 94±20 ml/min per 1.73 m2. The eGFR decline over 10 years was 38±13% in cases and 0±10% in controls. After adjustment for the matching variables plus albuminuria, systolic blood pressure, body mass index, and smoking, each 50% lower kidney clearance of isovalerylglycine, kynurenic acid, and xanthosine were associated with 1.4 to 2.2 greater odds of eGFR decline. Kynurenic acid exhibited the strongest association; each 50% lower clearance of this secretory solute was associated with 2.20-fold higher odds of eGFR decline (95% confidence interval [CI] 1.32-3.67). Conclusion: We found that in this community-based study of adults without significant kidney disease, lower proximal tubular secretory solute clearance is associated with future eGFR decline.
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Background: Significant racial and ethnic disparities in cardiovascular (CV) and kidney function outcomes in older adults with chronic kidney disease (CKD) have been reported. However, little is known about the extent to which these disparities exist in patients with CKD during the foundational period of young adulthood. The objective of this study was to determine risk factors and rates of CV disease and CKD progression in young adults with CKD across racial and ethnic groups. Methods: We studied all participants aged 21-40 years of age enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study (n=317). Baseline CV risk factors were described across racial and ethnic groups. Results: Outcomes included CV events or death (first incidence of heart failure, myocardial infarction, and stroke or death) and CKD progression (>50% decline in eGFR from baseline or end stage kidney disease [ESKD]). Incidence rate ratios (IRRs) were compared as a secondary analysis for participants identifying as Black or Hispanic with those identifying as White or another race and ethnicity. Adjusted models included age, sex, and per APOL1 high-risk allele. CV risk factors were higher in Black and Hispanic participants, including mean SBP, BMI, median UACr, and LDL. Black and Hispanic participants had higher incidence rates of HF (17.5 versus 5.1/1000 person-years), all-cause mortality (15.2 versus 7.1/1000 person-years), and CKD progression (125 versus 59/1000 person-years). Conclusions: In conclusion, we found a higher prevalence of CV risk factors, some modifiable, in young adults with CKD who identify as Black or Hispanic. Future strategies to ameliorate the racial and ethnic inequality in health outcomes earlier in life for patients with CKD should be prioritized.
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Doenças Cardiovasculares , Falência Renal Crônica , Insuficiência Renal Crônica , Adulto , Apolipoproteína L1 , Doenças Cardiovasculares/epidemiologia , Etnicidade , Humanos , Falência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Adulto JovemRESUMO
The ethics of returning nonactionable genetic research results to individuals are unclear. Apolipoprotein L1 (APOL1) genetic variants are nonactionable, predominantly found in people of West African ancestry, and contribute to kidney disease disparities. To inform ethical research practice, we interviewed researchers, clinicians, and African American community members (n = 76) about the potential risks and benefits of returning APOL1 research results. Stakeholders strongly supported returning APOL1 results. Benefits include reciprocity for participants, community education and rebuilding trust in research, and expectation of future actionability. Risks include analytic validity, misunderstanding, psychological burdens, stigma and discrimination, and questionable resource tradeoffs.Conclusions:APOL1 results should be offered to participants. Responsibly fulfilling this offer requires careful identification of best communication practices, broader education about the topic, and ongoing community engagement.
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Apolipoproteína L1 , Transplante de Rim , Negro ou Afro-Americano/psicologia , Apolipoproteína L1/genética , Predisposição Genética para Doença , Testes Genéticos/métodos , HumanosRESUMO
BACKGROUND: Commonly used estimated glomerular filtration rate (eGFR) equations include a Black race modifier (BRM) that was incorporated during equation derivation. Race is a social construct, and a poorly characterized variable that is applied inconsistently in clinical settings. The BRM results in higher eGFR for any creatinine concentration, implying fundamental differences in creatinine production or excretion in Black individuals compared to other populations. Equations without inclusion of the BRM have the potential to detect kidney disease earlier in patients at the greatest risk of chronic kidney disease (CKD), but also has the potential to over-diagnose CKD or impact downstream clinical interventions. The purpose of this study was to use an evidence-based approach to systematically evaluate the literature relevant to the performance of the eGFR equations with and without the BRM and to examine the clinical impact of the use or removal. CONTENT: PubMed and Embase databases were searched for studies comparing measured GFR to eGFR in racially diverse adult populations using the Modification of Diet in Renal Disease or the 2009-Chronic Kidney Disease Epidemiology Collaboration-creatinine equations based on standardized creatinine measurements. Additionally, we searched for studies comparing clinical use of eGFR calculated with and without the BRM. Here, 8632 unique publications were identified; an additional 3 studies were added post hoc. In total, 96 studies were subjected to further analysis and 44 studies were used to make a final assessment. SUMMARY: There is limited published evidence to support the use of a BRM in eGFR equations.
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Insuficiência Renal Crônica , Adulto , População Negra , Creatinina , Dieta , Taxa de Filtração Glomerular , Humanos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologiaRESUMO
RATIONALE & OBJECTIVE: Apolipoprotein L1 (APOL1) high-risk variants are associated with an increased risk for chronic kidney disease (CKD) among African Americans. Less is known regarding the risk for the development of CKD and kidney failure (end-stage kidney disease [ESKD]) among African Americans with only 1 APOL1 risk variant or whether the risk is modified by sickle cell trait. STUDY DESIGN: The Jackson Heart Study is a community-based longitudinal cohort study. SETTING & PARTICIPANTS: Self-reported African Americans in the Jackson Heart Study (n = 5,306). EXPOSURES: APOL1 G1 and G2 genotypes and sickle cell trait. OUTCOMES: Incident CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2), albuminuria (urinary albumin-creatinine ratio ≥ 30 mg/g), continuous and rapid kidney function decline (≥30% decline), and incident ESKD. ANALYTICAL APPROACH: Multivariable linear and logistic regression, and Cox proportional hazards models adjusted for age, sex, hypertension, diabetes, ancestry informative markers, and sickle cell trait. RESULTS: Of 2,300 participants, 41.3% had zero, 45.1% had 1, and 13.6% had 2 APOL1 risk variants. Sickle cell trait was present in 8.5%. Compared with participants with zero APOL1 risk variants, those with 2 alleles had an increased risk for incident albuminuria (adjusted HR [aHR], 1.88; 95% CI, 1.04 to 3.40), ESKD (aHR, 9.05; 95% CI, 1.79 to 45.85), incident CKD (aHR, 1.65; 95% CI, 1.06 to 2.57), continuous decline (ß = -1.90; 95% CI, -3.35 to -0.45), and rapid kidney function decline (OR, 2.21; 95% CI, 1.22 to 4.00) after adjustment for sickle cell trait, with similar results after adjustment for ancestry informative markers. Having 1 APOL1 risk variant was not associated with CKD outcomes and there was no interaction of APOL1 with sickle cell trait. LIMITATIONS: Single-site recruitment of African American individuals with APOL1 and sickle cell trait. CONCLUSIONS: The presence of 1 APOL1 risk allele was not associated with increased risk for CKD outcomes, whereas 2 risk alleles were associated with incident albuminuria, CKD, ESKD, and rapid and continuous kidney function decline. Additional studies are needed to determine factors that might alter the risk for adverse kidney outcomes among individuals with high-risk APOL1 genotypes.
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Background The majority of living organ donors are women, but few are deceased organ donors, which increases risks associated with sex mismatched organs. We sought to identify reasons for sex disparities in organ donation and strategies for equity. Methods and Results Using Amazon's Mechanical Turk, we examined US adults' perceptions regarding donation in a mixed-methods survey study. Results were compared by sex with Fisher's exact test and T-tests for quantitative results and qualitative descriptive analyses for write-in responses. Among 667 participants (55% women), the majority of men (64.8%) and women (63.4%) self-identified as registered donors. Women's willingness to donate their own organs to family members (P=0.03) or strangers (P=0.03) was significantly higher than men. Donors from both sexes were guided by: desire to help, personal experience, and believing organs would be useless to deceased donors. Non-donors from both sexes were guided by: no reason, medical mistrust, contemplating donation. When considering whether to donate organs of a deceased family member, women were equally guided by a family member's wishes and believing the family member had no further use for organs. Men had similar themes but valued the family member's wishes more. Among non-donors, both sexes would consider donation if more information was provided. Conclusions In a national survey, both sexes had similar reasons for becoming and not becoming an organ donor. However, compared with men, women were more willing to donate their organs to family members and strangers. Improving education and communicating wishes regarding organ donation with direct relatives may increase sex equity in deceased organ donation.