The elderly are the fastest growing subset of the US population. Age-associated increases in chronic disease and disability represent a significant financial burden on the healthcare system. Glomerular filtration rate (GFR) declines with age and low GFR defines chronic kidney disease (CKD). Many older adults have CKD, which is an important risk factor for adverse outcomes. Accurate assessment of GFR is central to clinical decision-making, assessment of the public health burden, and investigation into the epidemiology of CKD in older adults. However, there is active debate about what constitutes "normal" level of GFR in older adults and the best method to assess it. Creatinine based GFR estimates may not be accurate in older adults as malnutrition and loss of muscle mass, common with age and disease, affect serum creatinine independent of GFR. Cystatin C is an altnernative filtration marker not influenced by diet and muscle mass. The overall goal of this research is to explore the relationship of kidney function and aging.
Three aims are proposed: (1) Develop and validate GFR estimating eqations from cystatin C in the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) database (N>65 years= 1306). (2) Examine relationships among estimated GFR based on cystatin C, aging, nutrition, body composition, and mortality in the National Health and Nutrition Examination Survey (NHANES) (N>60 years= 7525). (3) Conduct a pilot study to examine the level of measured GFR in the general population of older adults (N=100) for subsequent implementation of ancillary studies to measure GFR in ongoing prospective cohort studies to provide information on normal levels of GFR across age and populations. A mentored, patient oriented Career Development Award is proposed to provide the candidate with rigorous methodological training and experience in clinical research related to kidney function and aging. The candidate proposes research projects and a career plan that includes didactic courses, expert advising, and mentored research to enhance the candidate's skills in complex statistical analyses of population based and longitudinal data, primary data collection and human subjects research, and to expand the candidate's kidney function and clinical geriatrics knowledge base. These projects and career development plan are consistent with the recognition by the Center for Disease Control of aging and chronic kidney disease as major public health problems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK081017-05
Application #
8257567
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2008-05-01
Project End
2013-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
5
Fiscal Year
2012
Total Cost
$169,668
Indirect Cost
$12,568
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
Juraschek, Stephen P; Coresh, Josef; Inker, Lesley A et al. (2013) Comparison of serum concentrations of ?-trace protein, ?2-microglobulin, cystatin C, and creatinine in the US population. Clin J Am Soc Nephrol 8:584-92
Viswanathan, Gautham; Sarnak, Mark J; Tighiouart, Hocine et al. (2013) The association of chronic kidney disease complications by albuminuria and glomerular filtration rate: a cross-sectional analysis. Clin Nephrol 80:29-39
Inker, Lesley A; Tonelli, Marcello; Hemmelgarn, Brenda R et al. (2012) Comparison of concurrent complications of CKD by 2 risk categorization systems. Am J Kidney Dis 59:372-81
Juraschek, Stephen P; Coresh, Josef; Inker, Lesley A et al. (2012) The effects of freeze-thaw on ?-trace protein and ?2-microglobulin assays after long-term sample storage. Clin Biochem 45:694-6
Tangri, Navdeep; Inker, Lesley A; Tighiouart, Hocine et al. (2012) Filtration markers may have prognostic value independent of glomerular filtration rate. J Am Soc Nephrol 23:351-9
Stevens, Lesley A; Li, Suying; Kurella Tamura, Manjula et al. (2011) Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) study equations: risk factors for and complications of CKD and mortality in the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis 57:S9-16
Inker, Lesley A; Eckfeldt, John; Levey, Andrew S et al. (2011) Expressing the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) cystatin C equations for estimating GFR with standardized serum cystatin C values. Am J Kidney Dis 58:682-4
Bowling, C Barrett; Inker, Lesley A; Gutierrez, Orlando M et al. (2011) Age-specific associations of reduced estimated glomerular filtration rate with concurrent chronic kidney disease complications. Clin J Am Soc Nephrol 6:2822-8
Stevens, Lesley A; Schmid, Christopher H; Greene, Tom et al. (2010) Comparative performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study equations for estimating GFR levels above 60 mL/min/1.73 m2. Am J Kidney Dis 56:486-95
Stevens, Lesley A; Li, Suying; Wang, Changchun et al. (2010) Prevalence of CKD and comorbid illness in elderly patients in the United States: results from the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis 55:S23-33

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