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Obesity and synergistic risk factors for chronic kidney disease in African American adults: the Jackson Heart Study.

ABSTRACT: Background:African Americans are at high risk for chronic kidney disease (CKD). Obesity may increase the risk for CKD by exacerbating features of the metabolic syndrome and promoting glomerular hyperfiltration. Whether other factors also affecting these pathways may amplify or mitigate obesity-CKD associations has not been investigated. Methods:We studied interactions between obesity and these candidate factors in 2043 African Americans without baseline kidney disease enrolled in the Jackson Heart Study. We quantified obesity as body mass index (BMI), sex-normalized waist circumference and visceral adipose volume measured by abdominal computed tomography at an interim study visit. Interactions were hypothesized with (i) metabolic risk factors (dietary quality and physical activity, both quantified by concordance with American Heart Association guidelines) and (ii) factors exacerbating or mitigating hyperfiltration (dietary protein intake, APOL1 risk status and use of renin-angiotensin system blocking medications). Using multivariable regression, we evaluated associations between obesity measures and incident CKD over the follow-up period, as well as interactions with metabolic and hyperfiltration factors. Results:Assessed after a median of 8?years (range 6-11?years), baseline BMI and waist circumference were not associated with incident CKD. Higher visceral adipose volume was independently associated with incident CKD (P?=?0.008) in a nonlinear fashion, but this effect was limited to those with lower dietary quality (P?=?0.001; P-interaction?=?0.04). In additional interaction models, higher waist circumference was associated with greater risk of incident CKD among those with the low-risk APOL1 genotype (P?=?0.04) but not those with a high-risk genotype (P-interaction?=?0.02). Other proposed factors did not modify obesity-CKD associations. Conclusions. Higher risks associated with metabolically active visceral adipose volume and interactions with dietary quality suggest that metabolic factors may be key determinants of obesity-associated CKD risk. Interactions between obesity and APOL1 genotype should be considered in studies of African Americans.

SUBMITTER: Olivo RE

PROVIDER: S-EPMC5982718 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Obesity and synergistic risk factors for chronic kidney disease in African American adults: the Jackson Heart Study.

Olivo Robert E RE Davenport Clemontina A CA Diamantidis Clarissa J CJ Bhavsar Nrupen A NA Tyson Crystal C CC Hall Rasheeda R Bidulescu Aurelian A Young Bessie B Mwasongwe Stanford E SE Pendergast Jane J Boulware L Ebony LE Scialla Julia J JJ

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20180601 6

<h4>Background</h4>African Americans are at high risk for chronic kidney disease (CKD). Obesity may increase the risk for CKD by exacerbating features of the metabolic syndrome and promoting glomerular hyperfiltration. Whether other factors also affecting these pathways may amplify or mitigate obesity-CKD associations has not been investigated.<h4>Methods</h4>We studied interactions between obesity and these candidate factors in 2043 African Americans without baseline kidney disease enrolled in ...[more]

PMID: 28992354

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Project description:BackgroundMelatonin is a hormone that is secreted at night by the pineal gland. It exerts its function by binding to the MT1 and MT2 receptors, which are encoded by the MTNR1A and MTNR1B genes, respectively. Previous studies reveal that MTNR1B variants are associated with insulin secretion impairments and an increased body mass index (BMI) in individuals of European and Asian ancestries. Obesity is highly prevalent in the US and disproportionately affects African Americans. Here, we hypothesized that common single nucleotide polymorphisms (SNPs) imputed in 1000 Genomes in the MTNR1B gene are associated with adiposity in African American adult men and women and that the association is modified by insomnia.MethodsWe used an additive genetic model to describe the association between the adiposity traits (BMI and waist circumference) and selected MTNR1B variants in 3,029 Jackson Heart Study participants, with an average age of 55.13 ± 12.84 years, and 62% were women. We regressed the adiposity measures on the estimated allelic or genotypic dosage at every selected SNP and adjusted for age, sex, population stratification, and insomnia. Thirty common SNPs, spanning the MTNR1B gene, with a minor allele frequency ≥ 5%, a call rate ≥ 90%, a Hardy-Weinberg equilibrium p value > 10-6, were available for the analysis.ResultsThe allele T of rs76371840 was associated with adiposity (OR = 1.47 [1.13-1.82]; PFDR-adjusted = 0.0499), and the allele A of rs8192552 showed a significant association with waist circumference (β = 0.023 ± 0.007; PFDR-adjusted = 0.0077) after correcting for multiple testing. When insomnia was included in the adiposity analysis model, the following four variants became significantly associated with adiposity: rs6483208; rs4388843; rs4601728; and rs12804291.ConclusionsOur data indicate that polymorphisms in the MTNR1B gene are associated with obesity traits in African Americans. To the best of our knowledge, this is the first study to explore the effect of insomnia on the association between the circadian MTNR1B genetic variants and metabolic traits in an African American sample population. We observed that insomnia affected the association between the MTNR1B variants and adiposity.

Project description:BackgroundRacial differences in rapid kidney function decline exist, but less is known regarding factors associated with rapid decline among African Americans. Greater understanding of potentially modifiable risk factors for early kidney function loss may help reduce the burden of kidney failure in this high-risk population.Study designProspective cohort study.Setting & participants3,653 African American participants enrolled in the Jackson Heart Study (JHS) with kidney function data from 2 of 3 examinations (2000-2004 and 2009-2013). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the CKD-EPI creatinine equation.PredictorsDemographics, socioeconomic status, lifestyle, and clinical risk factors for kidney failure.OutcomesRapid decline was defined as a ≥30% decline in eGFR during follow-up. We quantified the association of risk factors with rapid decline in multivariable models.MeasurementsClinical (systolic blood pressure and albuminuria [albumin-creatinine ratio]) and modifiable risk factors.ResultsMean age was 54±12 (SD) years, 37% were men, average body mass index was 31.8±7.1kg/m(2), 19% had diabetes mellitus (DM), and mean eGFR was 96.0±20mL/min/1.73m(2) with an annual rate of decline of 1.27mL/min/1.73m(2). Those with rapid decline (11.5%) were older, were more likely to be of low/middle income, and had higher systolic blood pressures and greater DM than those with nonrapid decline. Factors associated with ≥30% decline were older age (adjusted OR per 10 years older, 1.51; 95% CI, 1.34-1.71), cardiovascular disease (adjusted OR, 1.53; 95% CI, 1.12-2.10), higher systolic blood pressure (adjusted OR per 17mmHg greater, 1.22; 95% CI, 1.06-1.41), DM (adjusted OR, 2.63; 95% CI, 2.02-3.41), smoking (adjusted OR, 1.60; 95% CI, 1.10-2.31), and albumin-creatinine ratio > 30mg/g (adjusted OR, 1.55; 95% CI, 1.08-1.21). Conversely, results did not support associations of waist circumference, C-reactive protein level, and physical activity with rapid decline.LimitationsNo midstudy creatinine measurement at examination 2 (2005-2008).ConclusionsRapid decline heterogeneity exists among African Americans in JHS. Interventions targeting potentially modifiable factors may help reduce the incidence of kidney failure.

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Obesity and synergistic risk factors for chronic kidney disease in African American adults: the Jackson Heart Study.

Publications

Obesity and synergistic risk factors for chronic kidney disease in African American adults: the Jackson Heart Study.

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