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Abstract 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.

BackgroundNew Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race adjustment were developed to estimate the glomerular filtration rate (eGFR). We aimed to compare the performance of five CKD-EPI eGFR equations, with or without race, in predicting cardiovascular disease (CVD) events and all-cause mortality in Black Americans from the Jackson Heart Study.MethodsJHS is an ongoing population-based prospective cohort study of African Americans in the Jackson, Mississippi, metropolitan area. Five CKD-EPI equations were used to estimate GFR at baseline using serum creatinine (Cr) or cystatin C (cys), including 2009 eGFRcr(ASR [age, sex, race]), 2021 eGFRcr(AS [age and sex]), 2012 eGFRcr-cys(ASR), 2021 eGFRcr-cys(AS), 2012 eGFRcys(AS). Endpoints were incident CVD events and all-cause mortality. Cox proportional hazards regression was used to assess the associations between different eGFRs and outcomes adjusting for atherosclerotic risk factors. Harrell’s C-statistics and Net Reclassification Index (NRI) were used to assess the predictive utility.ResultsAmong 5,129 participants (average age 54.8 ± 12.8 yrs), 1898 were male (37.0%). eGFRcr(AS) provided lower estimates and resulting in a greater proportion of participants categorized as CKD than eGFRcr(ASR), eGFRcr-cys(ASR), eGFRcr-cys(AS) and eGFRcys(AS). A median follow-up of 13.7 and 14.3 years revealed 411 (9.3%) CVD incidents and 1,207 (23.5%) deaths. Lower eGFRs were associated with CVD incidents and all-cause mortality. eGFRcr-cys(ASR), eGFRcr-cys(AS) and eGFRcys(AS) were strongly associated with incident CVD events and all-cause mortality than eGFRcr(ASR) and eGFRcr(AS). A significant discrimination improvement was found in C-statistics for predicting incident CVD events and all-cause mortality after adding each eGFR measure to the basic model including atherosclerotic risk factors. Across a 7.5% 10-year risk threshold, eGFRcys(AS) improved net classification of all-cause mortality (NRI: 2.19, 95%CI: 0.08, 4.65%).ConclusioneGFR based on creatinine omit race has the lowest mean and detects more CKD patients in Black population. The eGFRs incorporating cystatin C strengthens the association between the eGFR and the risks of incident CVD and all-cause mortality. Cystatin C-based eGFR equations might be more appropriate for predicting CVD and mortality among Black population.

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.

Summary: Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p

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 (β = −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.

BackgroundControversy exists regarding the association of cigarette smoking and renal dysfunction, particularly among African Americans, who are disproportionately affected by chronic kidney disease; therefore, we evaluated the relationship between cigarette smoking and rapid renal function (RRF) decline in the Jackson Heart Study. Methods and ResultsRates of RRF decline were determined among 3648 African American participants enrolled at baseline in the Jackson Heart Study. RRF decline was defined as an absolute decline of estimated glomerular filtration rate of 30% from visit 1 to visit 3. There were 422 current, 659 past, and 2567 never smokers identified at visit 1. After adjustment for age, sex, body mass index, diabetes, hypertension, cholesterol, physical activity, education, alcohol consumption, and prevalent cardiovascular disease, current smokers demonstrated a significantly higher incidence of RRF decline compared with never smokers (incidence rate ratio 1.83, 95% CI 1.31–2.56). Current smokers using 1 to 19 and ≥20 cigarettes daily had an increased incidence of RRF decline (incidence rate ratios of 1.75 [95% CI 1.18–2.59] and 1.97 [95% CI 1.17–3.31], respectively). There was a significant, progressive reduction in estimated glomerular filtration rate from visit 1 to visit 3 in current and past smokers compared with never smokers. Finally, current smokers had a 1.38‐fold increase in C‐reactive protein compared with never smokers, after controlling for covariates. ConclusionsIn a large African American cohort, current cigarette smoking was independently associated with RRF decline in a dose‐dependent manner. There was also evidence of increased inflammation (C‐reactive protein) in current smokers, suggesting a potential mechanism for these relationships.

Patients with chronic diabetic complications experience high morbidity and mortality. Sex disparities in modifiable factors such as processes of care or self-care activities have not been explored in detail, particularly in these high-risk patients. Sex differences in processes of care and self-care activities were assessed in a cross-sectional analysis of the Pathways Study, an observational cohort of primary care diabetic patients from a managed care organization (N=4,839). Compared to men, women had decreased odds of dyslipidemia screening (adjusted odds ratio (AOR) 0.73, 95% CI 0.62–0.85), reaching low-density lipoprotein goal (AOR 0.70, 95% CI 0.58–0.86), and statin use (AOR 0.69, 95% CI 0.58–0.81); women had 19% greater odds of reaching hemoglobin A1c

Background. Survival statistics for daily haemodialysis are lacking as most centres providing this have treated only a small number of patients for short observation times. We pooled our 23-year, 1006-patient-year, five-centre experience of 415 patients treated by short daily haemodialysis. Methods. One hundred and fifty patients were treated in-centre, most because of medical complications and 265 by home or self-care haemodialysis. Patients were on daily haemodialysis for 29 ± 31 (0–272) months. Forty-two percent had primary and 31% had secondary renal failure. Treatment time was 136 ± 35 min, frequency 5.8 ± 0.5 times/week and weekly stdKt/V 2.7 ± 0.55. Results. Eighty-five patients (20%) died; 5-year cumulative survival was 68 ± 4.1% and 10-year survival was 42 ± 9%. Age, secondary renal failure and in-centre dialysis were associated with mortality, while gender, frequency of dialysis (5, 6 or 7 per week), continent, country and blood access were not. Survival was compared with matched patients from the USRDS 2005 Data Report using the standardized mortality ratio and cumulative survival curves. Both comparisons showed that the survival of the daily haemodialysis patients was 2–3 times higher and the predicted 50% survival time 2.3–10.9 years longer than that of the matched US haemodialysis patients. Survival of patients dialyzing daily at home was similar to that of age-matched recipients of deceased donor renal transplants. Conclusions. Survival of patients on short daily haemodialysis was 2–3 times better than that of matched three times weekly haemodialysis patients reported by the USRDS. [ABSTRACT FROM AUTHOR]

Objectives Social support may be an important mitigating factor against adverse cardiovascular outcomes by facilitating health-promoting behaviours or by buffering against the negative effects of stress. This study examined the association of social support with incident hypertension.Design Prospective cohort study.Setting We evaluated the association of social support with incident hypertension among participants in the Jackson Heart Study, a community-based cohort of African Americans.Participants This study included African American adults, who were free of hypertension at baseline (2000–2004). Functional social support, structural social support and satisfaction with social support were assessed at baseline among 1516, 1240 and 1503 participants, respectively.Outcome measures Incident hypertension was assessed at follow-up examinations in 2005–2008 and 2009–2013. Incident hypertension was defined by the first visit with systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg or self-reported antihypertensive medication use. Multivariable Poisson regression was used to estimate the association of baseline social support with incident hypertension, adjusting for relevant confounders.Results At baseline, the mean age of participants was 50 years and 64% were men. During a median follow-up time of 6.9 years, 54% of participants developed hypertension. A high level of functional social support was associated with lower risk of incident hypertension (incident rate ratio 0.64, (95% CI 0.41 to 0.97)), compared with a low level of functional social support. Level of structural social support and satisfaction with social support were not associated with hypertension risk.Conclusions These results suggest that greater functional support may be associated with a lower risk of incident hypertension.

Introduction Risk factors and mediators of associations of diabetes with COVID-19 outcomes are unclear.Research design and methods We identified all veterans receiving Department of Veterans Affairs healthcare with ≥1 positive nasal swab for SARS-CoV-2 (28 February–31 July 2020; n=35 879). We assessed associations of diabetes (with and without insulin use) with hospitalization, intensive care unit (ICU) admission, or death at 30 days, and with hazard of death until the censoring date. Among participants with diabetes (n=13 863), we examined associations of hemoglobin A1c and antihyperglycemic medication use with COVID-19 outcomes. We estimated mediation between diabetes and outcomes by comorbidities (cardiovascular disease, heart failure, and chronic kidney disease), statin or ACE inhibitor/angiotensin receptor blocker (ARB) use, and cardiac biomarkers (brain natriuretic peptide and troponin).Results Diabetes with and without insulin use was associated with greater odds of hospitalization, ICU admission, and death at 30 days, and with greater hazard of death compared with no diabetes (OR 1.73, 1.76 and 1.63, and HR 1.61; and OR 1.39, 1.49 and 1.33, and HR 1.37, respectively, all p

Co-inheritance of α-thalassemia has a significant protective effect on the severity of complications of sickle cell disease (SCD), including stroke. However, little information exists on the association and interactions for the common African ancestral α-thalassemia mutation (-α3.7 deletion) and β-globin traits (HbS trait [SCT] and HbC trait) on important clinical phenotypes such as red blood cell parameters, anemia, and chronic kidney disease (CKD). In a community-based cohort of 2,916 African Americans from the Jackson Heart Study, we confirmed the expected associations between SCT, HbC trait, and the -α3.7 deletion with lower mean corpuscular volume/mean corpuscular hemoglobin and higher red blood cell count and red cell distribution width. In addition to the recently recognized association of SCT with lower estimated glomerular filtration rate and glycated hemoglobin (HbA1c), we observed a novel association of the -α3.7 deletion with higher HbA1c levels. Co-inheritance of each additional copy of the -α3.7 deletion significantly lowered the risk of anemia and chronic kidney disease among individuals with SCT (P-interaction = 0.031 and 0.019, respectively). Furthermore, co-inheritance of a novel α-globin regulatory variant was associated with normalization of red cell parameters in individuals with the -α3.7 deletion and significantly negated the protective effect of α-thalassemia on stroke in 1,139 patients with sickle cell anemia from the Cooperative Study of Sickle Cell Disease (CSSCD) (P-interaction = 0.0049). Functional assays determined that rs11865131, located in the major alpha-globin enhancer MCS-R2, was the most likely causal variant. These findings suggest that common α- and β-globin variants interact to influence hematologic and clinical phenotypes in African Americans, with potential implications for risk-stratification and counseling of individuals with SCD and SCT.