Chronic kidney disease (CKD) is an important health problem in the elderly, with an increasing incidence of kidney failure and a high prevalence of earlier stages of CKD, with poor outcomes and high cost. It is well-known that GFR declines and albuminuria increases with aging, and that both are associated, independently and in combination, with an increased risk for kidney failure, complications of CKD and cardiovascular disease (CVD). However, the causes of age-related changes in kidney function are not well understood, in large part, due to absence of reliable information about the level of GFR in a representative elderly population. Our central hypothesis is that decreased GFR and increased albuminuria in the elderly reflect microvascular disease in the kidney due to exposure to CVD risk factors throughout the life course, mediated in part by increased aortic stiffness. The Age, Gene/Environment Susceptibility-Reykjavic Study (AGES-Reykjavik Study) (N01-AG-1-2100) is a genetic epidemiology study nested in a population based cohort study of CVD in Iceland begun in 1967. Iceland has a burden of CVD similar to the US Caucasian population. The study includes a comprehensive assessment of CVD risk factors in mid-life;vascular, neurocognitive, musckoskeletal and metabolic phenotypes of quantitative traits in late life;and a genome wide scan. We propose an ancillary study to the current visit.
Specific aims i nclude: 1. To determine the level of measured GFR by age, sex and CVD risk factors. We will measure GFR using plasma clearance of iohexol in a subcohort (N=800). 2. To determine the burden of CKD in aging. We will assay creatinine, cystatin C and albuminuria in all subjects (N=3484), relate them to CKD complications, clinical and subclinical CVD and CVD risk factors and compare the results to a comparable US population (NHANES 99-04). 3. To relate late-life kidney function to midlife and late-life CVD risk factors and late-life aortic stiffness. Measures of aortic stiffness were obtained in 940 subjects at the previous visit and will be obtained in all subjects at the current visit (N=3484). Measurement of GFR and aortic stiffness in a representative cohort of community dwelling elderly individuals will allow the most accurate investigation of the level of kidney function, burden of CKD, and potential mechanisms for the decline in kidney function with age. This information is essential for the identification of modifiable risk factors for development of CKD, as well as development of targeted strategies for prevention and treatment of CKD in the elderly. The principal investigator and research team are ideally suited to carry out this investigation. Their expertise, together with the unique design and comprehensive assessment in the AGES-Reykjavik Study, will allow for the most comprehensive and rigorous examination of relationships among kidney function, aortic stiffness and aging.

Public Health Relevance

Chronic kidney disease is a common problem in the elderly that is associated with an increased risk for kidney failure, complications of low kidney function and disease of the heart and blood vessels. Kidney function goes down with age but the cause is not completely understood and is thought to be related to high blood pressure caused by stiffening of the aorta that occurs with aging. This study will measure kidney function and stiffening of the aorta in a group of community dwelling older adults.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK082447-04
Application #
8463507
Study Section
Special Emphasis Panel (ZDK1-GRB-S (O3))
Program Officer
Narva, Andrew
Project Start
2010-05-01
Project End
2015-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
4
Fiscal Year
2013
Total Cost
$396,841
Indirect Cost
$108,161
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
Cooper, Leroy L; Woodard, Todd; Sigurdsson, Sigurdur et al. (2016) Cerebrovascular Damage Mediates Relations Between Aortic Stiffness and Memory. Hypertension 67:176-82
Inker, Lesley A; Tighiouart, Hocine; Coresh, Josef et al. (2016) GFR Estimation Using β-Trace Protein and β2-Microglobulin in CKD. Am J Kidney Dis 67:40-8
van Sloten, Thomas T; Mitchell, Gary F; Sigurdsson, Sigurdur et al. (2016) Associations between arterial stiffness, depressive symptoms and cerebral small vessel disease: cross-sectional findings from the AGES-Reykjavik Study. J Psychiatry Neurosci 41:162-8
Zachariah, Justin P; Hwang, Susan; Hamburg, Naomi M et al. (2016) Circulating Adipokines and Vascular Function: Cross-Sectional Associations in a Community-Based Cohort. Hypertension 67:294-300
Okparavero, Aghogho; Foster, Meredith C; Tighiouart, Hocine et al. (2016) Prevalence and complications of chronic kidney disease in a representative elderly population in Iceland. Nephrol Dial Transplant 31:439-47
Bell, Vanessa; Sigurdsson, Sigurdur; Westenberg, Jos J M et al. (2015) Relations between aortic stiffness and left ventricular structure and function in older participants in the Age, Gene/Environment Susceptibility--Reykjavik Study. Circ Cardiovasc Imaging 8:e003039
Mitchell, Gary F (2015) Does Measurement of Central Blood Pressure have Treatment Consequences in the Clinical Praxis? Curr Hypertens Rep 17:66
Bell, Vanessa; Mitchell, Gary F (2015) Influence of vascular function and pulsatile hemodynamics on cardiac function. Curr Hypertens Rep 17:580
Woodard, Todd; Sigurdsson, Sigurdur; Gotal, John D et al. (2015) Segmental kidney volumes measured by dynamic contrast-enhanced magnetic resonance imaging and their association with CKD in older people. Am J Kidney Dis 65:41-8
Inker, Lesley A; Okparavero, Aghogho; Tighiouart, Hocine et al. (2015) Midlife Blood Pressure and Late-Life GFR and Albuminuria: An Elderly General Population Cohort. Am J Kidney Dis 66:240-8

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