Age and cystatin C in healthy adults: a collaborative study

Michelle C. Odden 1 3 12 Ira B. Tager 3 12 Ron T. Gansevoort 0 12 Stephan J. L. Bakker 0 12 Ronit Katz 7 12 Linda F. Fried 6 12 Anne B. Newman 5 12 Robert B. Canada 4 12 Tamara Harris 9 12 Mark J. Sarnak 8 12 David Siscovick 2 12 Michael G. Shlipak 10 11 12 0 Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands 1 Department of General Internal Medicine, University of California , San Francisco, CA, USA 2 Departments of Medicine and Epidemiology, University of Washington , Seattle WA 3 Department of Epidemiology, School of Public Health, University of California , Berkeley 4 Departments of Medicine and Nephrology, University of Tennessee Health Science Center , Memphis, TN 5 Department of Epidemiology, University of Pittsburgh School of Medicine , Pittsburgh, PA 6 Renal Section, Veterans Affairs Pittsburgh Healthcare System 7 Collaborative Health Studies Coordinating Center, University of Washington , Seattle, WA 8 Division of Nephrology, Department of Medicine, Tufts Medical Center , Boston, MA 9 Laboratory of Epidemiology , Demography, and Biometry Program, National Institute on Aging , NIH, Bethesda, MD 10 Departments of Medicine, Epidemiology and Biostatistics, University of California , San Francisco 11 Department of General Internal Medicine, San Francisco VA Medical Center , San Francisco, CA, USA 12 Division of Nephrology, Department of Internal Medicine, School of Medicine, Ewha Medical Research Center, Ewha Womans University , Seoul, Korea Background. Kidney function declines with age, but a substantial portion of this decline has been attributed to the higher prevalence of risk factors for kidney disease at older ages. The effect of age on kidney function has not been well described in a healthy population across a wide age spectrum. Methods. The authors pooled individual-level crosssectional data from 18 253 persons aged 28-100 years in four studies: the Cardiovascular Health Study; the Health, Aging and Body Composition Study; the Multi-Ethnic Study of Atherosclerosis and the Prevention of Renal and C The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail: - Received for publication: 10.3.09; Accepted in revised form: 19.8.09 Vascular End-Stage Disease cohort. Kidney function was measured by cystatin C. Clinical risk factors for kidney disease included diabetes, hypertension, obesity, smoking, coronary heart disease, cerebrovascular disease, peripheral arterial disease and heart failure. Results. Across the age range, there was a strong, nonlinear association of age with cystatin C concentration. This association was substantial, even among participants free of clinical risk factors for kidney disease; mean cystatin C levels were 46% higher in participants 80 and older compared with those <40 years (1.06 versus 0.72 mg/L, P < 0.001). Participants with one or more risk factors had higher cystatin C concentrations for a given age, and the age association was slightly stronger (P < 0.001 for age and risk factor interaction). Conclusions. There is a strong, non-linear association of age with kidney function, even in healthy individuals. An important area for research will be to investigate the mechanisms that lead to deterioration of kidney function in apparently healthy persons. Introduction Kidney disease disproportionately affects older persons; the incidence of end-stage renal disease increases with age and the majority of subjects who initiate renal replacement therapy are over 60 years of age [1,2]. Although the strong association between age and kidney function is well established [3], it is unclear what portion of this decline is due to the higher prevalence of risk factors for kidney disease at older ages, such as hypertension, diabetes and vascular disease [4]. The inclusion of persons with these comorbid conditions in prior descriptive studies of kidney function may have inaccurately attributed the risk factorrelated decline in kidney function to ageing [5]. A greater understanding of age-related decline in kidney function in a clinically healthy population will inform studies aimed at prevention of kidney disease and its related morbidity in the elderly. Adding to the complexity of describing age-associated changes in kidney function has been the use of creatininebased measures in most prior epidemiologic studies. Serum creatinine concentrations are influenced by several factors other than glomerular filtration rate (GFR) including sex, body composition, activity, dietary intake and health status [6]. Older persons may have normal serum creatinine concentrations, despite the presence of kidney dysfunction [7]. Cystatin C is an alternative measure of kidney function that is a better estimate of GFR compared with serum creatinine in the elderly [810]. The present study combined cross-sectional data from four studies: the Cardiovascular Health Study (CHS); the Health, Aging and Body Composition Study (Health ABC); the Multi-Ethnic Study of Atherosclerosis (MESA) and the Prevention of Renal and Vascular End-Stage Disease cohort (PREVEND). The recent availability of cystatin C measurements in several large studies has afforded the opportunity to characterize cystatin C concentrations in 18 000 individuals aged 28100 years. The goal of this study was to examine cystatin C concentrations across adulthood to characterize the association of age with kidney function in a healthy population and to compare this association to that in persons with clinical risk factors for kidney disease. Subjects and methods Study population The CHS aimed to evaluate risk factors for the development and progression of cardiovascular disease in the elderly [11]. The study recruited persons from Medicare eligibility lists in Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania in 19891990 for the original cohort and 19921993 for a supplementary enrolment period designed to increase the number of African American participants. To be considered eligible for the study, persons had to meet the following criteria: (1) age 65 years; (2) not institutionalized; (3) expected to remain in the current community for 3 years or longer; (4) not under active treatment for cancer; and (5) able to give informed consent without requiring a proxy respondent. The Health ABC study was designed to examine the relation between age-related changes of health and body composition and incident functional limitations in initially well-functioning black and white adults aged 7079 years. Each of the two study sites, Pittsburgh, PA and Memphis, TN, recruited participants from a list of Medicare beneficiaries between April 1997 and June 1998. Inclusion criteria were (1) reported ability to walk one-quarter mile, climb ten steps and perform basic activities of dail (...truncated)