Dataset Information

Interaction between GFR and risk factors for morbidity and mortality in African Americans with CKD.

ABSTRACT:

Background and objectives

The African American Study of Kidney Disease Trial identified risk factors for CKD progression and suggested that GFR level may modify the association between these risk factors and CKD progression or death.

Design, setting, participants, & measurements

Enrollment in the African American Study of Kidney Disease Trial occurred between June of 1995 and September of 2001, with median follow-up of 48.6 months. Among 1094 patients with hypertensive kidney disease in the trial, this study tested whether the association between six previously identified risk factors for CKD progression (or death) and a composite clinical outcome (progression of CKD, ESRD, or death) depends on level of GFR. Multivariate Cox regression was used to control for other baseline risk factors.

Results

After controlling for baseline risk factors, only proteinuria was more closely associated with the composite clinical outcome at lower levels of GFR (P value for interaction term=0.002); increased hazards of the clinical composite outcome associated with a doubling of proteinuria ranged from 30% (95% confidence interval=21%-39%) with a GFR of 50 to 55% (95% confidence interval=40%-72%) with a GFR of 25.

Conclusions

The magnitude of the association between proteinuria and CKD progression, ESRD, or death in the African American Study of Kidney Disease Trial cohort depends on the level of GFR; proteinuria is a stronger independent predictor of the composite clinical outcome at lower levels of GFR. This finding reinforces that African Americans with proteinuria and lower GFR represent a population at particularly high risk for adverse outcomes.

SUBMITTER: Erickson KF

PROVIDER: S-EPMC3531654 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Publications

Interaction between GFR and risk factors for morbidity and mortality in African Americans with CKD.

Erickson Kevin F KF Lea Janice J McClellan William M WM

Clinical journal of the American Society of Nephrology : CJASN 20121018 1

<h4>Background and objectives</h4>The African American Study of Kidney Disease Trial identified risk factors for CKD progression and suggested that GFR level may modify the association between these risk factors and CKD progression or death.<h4>Design, setting, participants, & measurements</h4>Enrollment in the African American Study of Kidney Disease Trial occurred between June of 1995 and September of 2001, with median follow-up of 48.6 months. Among 1094 patients with hypertensive kidney dise ...[more]

PMID: 23085727

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Project description:ObjectivesTo examine associations between inflammation and physical function and potential mediation by white matter hyperintensities (WMHs) in African Americans (AAs) and European Americans (EAs).DesignCross-sectional analysis using linear and logistic models with generalized estimating equations to account for family clustering, reporting results as regression coefficients (β) and odds ratios (ORs) adjusted for education, alcohol, exercise, body mass index, hypertension, diabetes mellitus, heart disease, cognition, ankle-brachial index, race (site), and supported interactions.SettingGenetic Epidemiology Network of Arteriopathy-Genetics of Microangiopathic Brain Injury Study cohort.ParticipantsAA and EA sibships with two or more siblings with hypertension before age 60 (N = 1,960; 65% female, 51% AA, aged 26-91, 50% obese, 72% hypertensive).MeasurementsInflammation (C-reactive protein (CRP), interleukin-6 (IL6), soluble tumor necrosis factor receptors (sTNFRs) 1 and 2, WMH volume (cm(3) ) according to magnetic resonance imaging), walking speed (cm/s) over 25 feet, and mobility difficulty (any self-reported difficulty walking half a mile).ResultsIn separate models, inflammatory markers were associated with walking speed (sTNFR1: β = -2.74, P < .001; sTNFR2: β = -1.23, P = .03; CRP: β = -1.95, P = .001; IL6: β = -1.24, P = .03) and mobility difficulty (sTNFR1: OR = 1.36, P = .001; sTNFR2: OR = 1.25, P = .005; CRP: OR = 1.22, P = .005; IL6: OR = 1.18, P = .02); the association between WMH volume and sTNFR1 in AA (β = 0.07, P = .06) did not reach typical statistical thresholds. WMH volume was associated with walking speed in AA (β = -3.17, P = .02) but not with mobility difficulty (OR = 1.10, P = .54). Adjusting for WMH did not change associations.ConclusionIn young, middle-aged, and older adults with prevalent cardiovascular risk factors, multiple inflammatory biomarkers were associated with slower walking speed independent of microvascular disease in the brain. There was little evidence of mediation by brain WMH volume. Inflammation may contribute to physical function impairments through pathways other than brain microvascular disease, particularly in AAs.

Project description:Novel biomarkers that more accurately reflect kidney function and predict future CKD are needed. The human metabolome is the product of multiple physiologic or pathophysiologic processes and may provide novel insight into disease etiology and progression. This study investigated whether estimated kidney function would be associated with multiple metabolites and whether selected metabolomic factors would be independent risk factors for incident CKD.In total, 1921 African Americans free of CKD with a median of 19.6 years follow-up among the Atherosclerosis Risk in Communities Study were included. A total of 204 serum metabolites quantified by untargeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry was analyzed by both linear regression for the cross-sectional associations with eGFR (specified by the Chronic Kidney Disease Epidemiology Collaboration equation) and Cox proportional hazards model for the longitudinal associations with incident CKD.Forty named and 34 unnamed metabolites were found to be associated with eGFR specified by the Chronic Kidney Disease Epidemiology Collaboration equation with creatine and 3-indoxyl sulfate showing the strongest positive (2.8 ml/min per 1.73 m(2) per +1 SD; 95% confidence interval, 2.1 to 3.5) and negative association (-14.2 ml/min per 1.73 m(2) per +1 SD; 95% confidence interval, -17.0 to -11.3), respectively. Two hundred four incident CKD events with a median follow-up time of 19.6 years were included in the survival analyses. Higher levels of 5-oxoproline (hazard ratio, 0.70; 95% confidence interval, 0.60 to 0.82) and 1,5-anhydroglucitol (hazard ratio, 0.68; 95% confidence interval, 0.58 to 0.80) were significantly related to lower risk of incident CKD, and the associations did not appreciably change when mutually adjusted.These data identify a large number of metabolites associated with kidney function as well as two metabolites that are candidate risk factors for CKD and may provide new insights into CKD biomarker identification.

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Project description:BackgroundCardiac structural abnormalities, common in African Americans, are associated with adverse clinical outcomes. Associations between echocardiography-measured subclinical heart failure and kidney function decline are unknown and may identify novel risk factors for kidney disease in this population.Study designProspective cohort study.Setting & participants2,418 Jackson Heart Study participants with baseline echocardiograms and longitudinal measures of estimated glomerular filtration rate (eGFR) calculated from the CKD-EPI creatinine equation. 2,219 participants had baseline eGFRs≥60mL/min/1.73m2.PredictorsLeft ventricular mass (LVM) and ejection fraction (LVEF) and pulmonary artery systolic pressure (PASP) quantified from baseline echocardiograms.OutcomesPrimary outcome was >30% eGFR decline or progression to end-stage renal disease (ESRD; need for dialysis therapy) over a mean of 8 years. Secondary outcome, eGFR<60mL/min/1.73m2 or progression to ESRD and eGFR decline >1mL/min/1.73m2 per year among those with baseline eGFRs≥60mL/min/1.73m2.MeasurementsLogistic regression models, adjusted for demographics, physical characteristics, comorbid conditions, and medication use.ResultsMean age was 52.2±11.9 (SD) years, 37% of participants were men; mean baseline eGFR was 87.3±17.3mL/min/1.73m2. The primary and secondary outcomes occurred in 148 (6.1%) and 162 (7.1%) participants, respectively. In unadjusted models, every 25-g greater LVM was significantly associated with greater odds of eGFR decline > 30% or ESRD (OR, 1.38; 95% CI, 1.26-1.51) and incident eGFR<60mL/min/1.73m2 or ESRD (OR, 1.30; 95% CI, 1.20-1.42); only the former remained statistically significant after adjustment. There was no association of LVEF or PASP with either eGFR decline > 30% or ESRD (LVEF: adjusted OR, 0.95 [95% CI, 0.84-1.07]; PASP: adjusted OR, 0.98 [95% CI, 0.87-1.11]) or incident eGFR<60mL/min/1.73m2 or ESRD (LVEF: adjusted OR, 0.98 [95% CI, 0.86-1.11]; PASP: adjusted OR, 1.05 [95% CI, 0.94-1.18]) in multivariable models.LimitationsNo midstudy creatinine measurement at examination 2.ConclusionsGreater LVM was significantly associated with eGFR decline > 30% or ESRD among African Americans in a community-based cohort. Treating and reversing elevated LVM may reduce the burden and progression of kidney disease in this high-risk population.

Dataset Information

Interaction between GFR and risk factors for morbidity and mortality in African Americans with CKD.

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Publications

Interaction between GFR and risk factors for morbidity and mortality in African Americans with CKD.

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