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Kidney Function and Fracture Risk: The Atherosclerosis Risk in Communities (ARIC) Study.

ABSTRACT: People with end-stage renal disease are at high risk for bone fracture. Less is known about fracture risk in milder chronic kidney disease and whether chronic kidney disease-associated fracture risk varies by sex or assessment with alternative kidney markers.Prospective cohort study.10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011.Kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFRcr), urine albumin-creatinine ratio, and alternative filtration markers.Fracture-related hospitalizations determined by diagnostic code.Baseline kidney markers; hospitalizations identified by self-report during annual telephone contact and active surveillance of local hospital discharge lists.Mean age of participants was 63 years, 56% were women, and 22% were black. During a median follow-up of 13 years, there were 722 incident fracture-related hospitalizations. Older age, female sex, and white race were associated with higher risk for fracture (P<0.001). The relationship between eGFRcr and fracture risk was nonlinear: <60mL/min/1.73m(2), lower eGFRcr was associated with higher fracture risk (adjusted HR per 10mL/min/1.73m(2) lower, 1.24; 95% CI, 1.05-1.47); there was no statistically significant association for ?60mL/min/1.73m(2) in the primary analysis. In contrast, there was a graded association between other markers of kidney function and subsequent fracture, including albumin-creatinine ratio (HR per doubling, 1.10; 95% CI, 1.06-1.14), cystatin C-based eGFR (HR per 1-SD decrease, 1.15; 95% CI, 1.06-1.25), and 1/?2-microglobulin (HR per 1-SD decrease, 1.26, 95% CI, 1.15-1.37).No bone mineral density assessment; one-time measurement of kidney function.Both low eGFR and higher albuminuria were significant risk factors for fracture in this community-based population. The shape of the association in the upper ranges of eGFR varied by the filtration marker used in estimation.

SUBMITTER: Daya N

PROVIDER: S-EPMC4724513 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Kidney Function and Fracture Risk: The Atherosclerosis Risk in Communities (ARIC) Study.

Daya Natalie N Voskertchian Annie A Schneider Andrea L C ALC Ballew Shoshana S McAdams DeMarco Mara M Coresh Josef J Appel Lawrence J LJ Selvin Elizabeth E Grams Morgan E ME

American journal of kidney diseases : the official journal of the National Kidney Foundation 20150804 2

<h4>Background</h4>People with end-stage renal disease are at high risk for bone fracture. Less is known about fracture risk in milder chronic kidney disease and whether chronic kidney disease-associated fracture risk varies by sex or assessment with alternative kidney markers.<h4>Study design</h4>Prospective cohort study.<h4>Setting & participants</h4>10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011.<h4>Predictor</h4>Kidney function as ...[more]

PMID: 26250781

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Project description:BackgroundFrail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals.Study designObservational study.Setting & participants4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013).PredictorsKidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr) and serum cystatin C level (eGFRcys) and urine albumin-creatinine ratio.OutcomeFrailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity).Results341 (7%) participants were classified as frail, 1,475 (30%) had eGFRcr<60mL/min/1.73m2, 2,480 (50%) had eGFRcys<60mL/min/1.73m2, and 1,006 (20%) had albuminuria with albumin excretion ≥ 30mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys<60mL/min/1.73m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and albumin-creatinine ratio. Frail individuals with eGFRcr of 60 to <75mL/min/1.73m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45-<60, 32% to 30-<45, and 3% to <30mL/min/1.73m2). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants).LimitationsCross-sectional study design.ConclusionsFrail individuals had a high prevalence of reduced kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr. Given the substantial medication burden and uncertainty in chronic kidney disease classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population.

Project description:BACKGROUND:Reduced lung function is associated with clinical outcomes such as cardiovascular disease. However, little is known about its association with incident end-stage renal disease (ESRD) and chronic kidney disease (CKD). STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:14,946 participants aged 45 to 64 years at baseline (1987-1989) in the Atherosclerosis Risk in Communities (ARIC) Study (45.0% men and 25.2% black), with follow-up through 2012. PREDICTORS:Race- and sex-specific quartiles of percent-predicted forced vital capacity (FVC) and the proportion of forced expiratory volume in 1 second of expiration to FVC (FEV1/FVC) at baseline determined with spirometry. OUTCOMES:Incident ESRD (defined here as renal replacement therapy or death due to CKD) as the primary outcome and incident CKD (defined here as ESRD, ?25% decline in estimated glomerular filtration rate to a level <60mL/min/1.73m2, or CKD-related hospitalizations/deaths) as the secondary outcome. RESULTS:During a median follow-up of 23.6 years, 526 (3.5%) participants developed ESRD. After adjusting for potential confounders, the cause-specific HR of incident ESRD for the lowest (vs highest) quartile was 1.72 (95% CI, 1.31-2.26) for percent-predicted FVC and 1.33 (95% CI, 1.03-1.73) for FEV1/FVC. Compared to a high-normal lung function pattern, a mixed pattern (ie, percent-predicted FVC<80% and FEV1/FVC<70%; 3.4% of participants) demonstrated the highest adjusted cause-specific HR of ESRD at 2.28 (95% CI, 1.50-3.45), followed by the restrictive pattern (ie, percent-predicted FVC<80% and FEV1/FVC?70%; 4.8% of participants) at 2.03 (95% CI, 1.47-2.81), obstructive pattern (ie, percent-predicted FVC?80% and FEV1/FVC<70%; 18.9% of participants) at 1.47 (95% CI, 1.09-1.99), and low-normal pattern (ie, percent-predicted FVC 80%-<100% and FEV1/FVC?70%, or percent-predicted FVC?80% and FEV1/FVC 70%-<75%; 44.3% of participants) at 1.21 (95% CI, 0.94-1.55). Similar associations were seen with incident CKD. LIMITATIONS:Limited number of participants with moderate/severe lung dysfunction and spirometry only at baseline. CONCLUSIONS:Reduced lung function, particularly lower percent-predicted FVC, is independently associated with CKD progression. Our findings suggest a potential pathophysiologic contribution of reduced lung function to the development of CKD and a need for monitoring kidney function in persons with reduced lung function.

Project description:RATIONALE & OBJECTIVE:The relationship between hypertension, antihypertension medication use, and change in glomerular filtration rate (GFR) over time among individuals with preserved GFR requires investigation. STUDY DESIGN:Observational study. SETTING & PARTICIPANTS:14,854 participants from the Atherosclerosis Risk in Communities (ARIC) Study. PREDICTORS:Baseline hypertension status (1987-1989) was categorized according to the 2017 American College of Cardiology/American Heart Association Clinical Practice Guideline as normal blood pressure, elevated blood pressure, stage 1 hypertension, stage 2 hypertension without medication, or stage 2 hypertension with medication. OUTCOMES:Slope of estimated GFR (eGFR) at 5 study visits over 30 years. ANALYTICAL APPROACH:Mixed models with random intercepts and random slopes were fit to evaluate the association between baseline hypertension status and slope of eGFR. RESULTS:At baseline, 13.2%, 7.3%, and 19.4% of whites and 15.8%, 14.9%, and 39.9% of African Americans had stage 1 hypertension, stage 2 hypertension without medication, and stage 2 hypertension with medication. Compared with those with normal blood pressure, the annual eGFR decline was greater in people with higher blood pressure (whites: elevated blood pressure, -0.11mL/min/1.73m2; stage 1 hypertension, -0.15mL/min/1.73m2; stage 2 hypertension without medication, -0.36mL/min/1.73m2; stage 2 hypertension with medication, -0.17mL/min/1.73m2; African Americans: elevated blood pressure, -0.21mL/min/1.73m2; stage 1 hypertension, -0.16mL/min/1.73m2; stage 2 hypertension without medication, -0.50mL/min/1.73m2; stage 2 hypertension with medication, -0.16mL/min/1.73m2). The 30-year predicted probabilities of developing chronic kidney disease stage G3a+with normal blood pressure, elevated blood pressure, stage 1 hypertension, stage 2 hypertension without medication, or stage 2 hypertension with medication among whites were 54.4%, 61.6%, 64.7%, 78.1%, and 70.9%, respectively, and 55.4%, 62.8%, 60.9%, 76.1%, and 66.6% among African Americans. LIMITATIONS:Slope estimated using a maximum of 5 eGFR assessments; differential loss to follow-up. CONCLUSIONS:Compared to normotension, baseline hypertension status was associated with faster kidney function decline over 30-year follow-up in a general population cohort. This difference was attenuated among people using antihypertensive medications.

Project description:Rationale & objectiveObesity has been related to risk for chronic kidney disease. However, the associations of different measures of midlife obesity with long-term kidney function trajectories and whether they differ by sex and race are unknown.Study designObservational study.Setting & participants13,496 participants from the Atherosclerosis Risk in Communities (ARIC) Study.PredictorsMidlife obesity status as measured by body mass index (BMI), waist-to-hip ratio, and predicted percent fat at baseline.OutcomesEstimated glomerular filtration rate (eGFR) calculated using serum creatinine level measured at 5 study visits, and incident kidney failure with replacement therapy (KFRT).Analytical approachMixed models with random intercepts and random slopes for eGFR. Cox proportional hazards models for KFRT.ResultsBaseline mean age was 54 years, median eGFR was 103mL/min/1.73m2, and median BMI was 27kg/m2. Over 30 years of follow-up, midlife obesity measures were associated with eGFR decline in White and Black women but not consistently in men. Adjusted for age, center, smoking, and coronary heart disease, the differences in eGFR slope per 1-SD higher BMI, waist-to-hip ratio, and predicted percent fat were 0.09 (95% CI, -0.18 to 0.36), -0.25 (95% CI, -0.50 to 0.01), and-0.14 (95% CI, -0.41 to 0.13) mL/min/1.73m2 per decade for White men; -0.91 (95% CI, -1.15 to-0.67), -0.82 (95% CI, -1.06 to-0.58), and-1.02 (95% CI, -1.26 to-0.78) mL/min/1.73m2 per decade for White women; -0.70 (95% CI, -1.54 to 0.14), -1.60 (95% CI, -2.42 to-0.78), and-1.24 (95% CI, -2.08 to-0.40) mL/min/1.73m2 per decade for Black men; and-1.24 (95% CI, -2.08 to-0.40), -1.50 (95% CI, -2.05 to-0.95), and-1.43 (95% CI, -2.00 to-0.86) mL/min/1.73m2 per decade for Black women. Obesity indicators were independently associated with risk for KFRT for all sex-race groups except White men.LimitationsLoss to follow-up during 3 decades of follow-up with 5 eGFR assessments.ConclusionsObesity status is a risk factor for future decline in kidney function and development of KFRT in Black and White women, with less consistent associations among men.

Project description:Decreased kidney function and kidney damage may predate hypertension, but only a few studies have investigated both types of markers simultaneously, and these studies have obtained conflicting results.Cross-sectional for prevalent and prospective observational study for incident hypertension.9,593 participants from the ARIC (Atherosclerosis Risk in Communities) Study, aged 53-75 years in 1996-1998.Several markers of kidney function (estimated glomerular filtration rate using serum creatinine and/or cystatin C and 2 novel markers [?-trace protein and ?2-microglobulin]) and 1 marker of kidney damage (urinary albumin-creatinine ratio [ACR]). Every kidney marker was categorized by its quintiles (top quintile as a reference for estimated glomerular filtration rates and bottom quintile for the rest).Prevalent and incident hypertension.Prevalence ratios and HRs of hypertension based on modified Poisson regression and Cox proportional hazards models, respectively.There were 4,378 participants (45.6%) with prevalent hypertension at baseline and 2,175 incident hypertension cases during a median follow-up of 9.8 years. Although all 5 kidney function markers were associated significantly with prevalent hypertension, prevalent hypertension was associated most notably with higher ACR (adjusted prevalence ratio, 1.60 [95% CI, 1.50-1.71] for the highest vs lowest ACR quintile). Similarly, ACR was associated consistently with incident hypertension in all models tested (adjusted HR, 1.28 [95% CI, 1.10-1.49] for top quintile), while kidney function markers demonstrated significant associations in some, but not all, models. Even mildly increased ACR (9.14-14.0mg/g) was associated significantly with incident hypertension.Self-reported use of antihypertensive medication for defining incident hypertension, single assessment of kidney markers, and relatively narrow age range.Although all kidney markers were associated with prevalent hypertension, only elevated albuminuria was associated consistently with incident hypertension, suggesting that kidney damage is related more closely to hypertension than moderate reduction in overall kidney function.

Project description:<p>The Atherosclerosis Risk in Communities (ARIC) Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective epidemiologic study conducted in four U.S. communities. The four communities are Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date.</p> <p>ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were reexamined every three years with the first screen (baseline) occurring in 1987-89, the second in 1990-92, the third in 1993-95, and the fourth and last exam was in 1996-98. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort.</p> <p>In the Community Surveillance Component, currently ongoing, these four communities are investigated to determine the community-wide occurrence of hospitalized myocardial infarction and coronary heart disease deaths in men and women aged 35-84 years. Hospitalized stroke is investigated in cohort participants only. Starting in 2006, the study conducts community surveillance of inpatient (ages 55 years and older) and outpatient heart failure (ages 65 years and older) for heart failure events beginning in 2005.</p> <p>ARIC is currently funded through January 31, 2012.</p> <p>This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to atherosclerosis and cardiovascular disease through large-scale genome-wide association studies of well-characterized cohorts of adults in four defined populations. Genotyping was performed at the Broad Institute of MIT and Harvard, a GENEVA genotyping center. Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.</p>

Dataset Information

Kidney Function and Fracture Risk: The Atherosclerosis Risk in Communities (ARIC) Study.

Publications

Kidney Function and Fracture Risk: The Atherosclerosis Risk in Communities (ARIC) Study.

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