This protocol will evaluate the utility of the two GFR markers, creatinine and cystatin C, in comparison with measured glomerular filtration rate (GFR) by iohexol clearance in 375 Black and White adult participants of the population-based Multi-ethnic Study of Atherosclerosis (MESA) cohort from the Johns Hopkins clinical center. Although GFR estimation by creatinine has improved over the past decade, there has been inadequate inclusion of persons over 65 years of age, and no study of GFR measurement has occurred within a population-based sample of Blacks and Whites in the United States. To advance the detection and definition of CKD across a broad age range of diverse adults,, we must focus on the higher ranges of GFR, and we must identify the optimal strategy for GFR estimation.
The first Aim of this cross-sectional study will be to determine the influence of Black race-ethnicity on serum levels of filtration markers (creatinine and cystatin C) in the general population, and to modify current GFR equations to capture optimally the influence of Black race.
The second Aim will be: to evaluate age-related decline in GFR; to compare the relative ability of the filtration markers to capture declining GFR with age; and, to modify current GFR equations to incorporate the influence of age. In executing these Aims, we will determine the optimal biomarker(s) for GFR estimation ? creatinine, cystatin C, or both. In addition, blood specimens will be stored with the potential for examination of future filtration markers. To accomplish our objectives, we will measure iohexol-GFR in approximately 375 Black and White MESA participants, spanning a target age range of 55-95. This study could be a major contributor to the National Institute of Health?s efforts to address the persistent racial disparities in the burden of kidney disease in the United States.

Public Health Relevance

Chronic kidney disease is a public health problem that disproportionately affects racial and ethnic minorities in the US. The normal levels of kidney function and the accuracy of equations to estimate kidney function are not known in racial and ethnic minorities, which represent barriers to effective clinical practice, research and public health efforts for CKD in these groups. The goals of the proposed project are to characterize the usual levels of kidney function in racial and ethnic minorities; to develop more accurate ways to estimate kidney function in racial and ethnic groups.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-S (O2))
Program Officer
Narva, Andrew
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Tufts University
United States
Zip Code
Foster, Meredith C; Levey, Andrew S; Inker, Lesley A et al. (2017) Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly: AGES-Kidney and MESA-Kidney. Am J Kidney Dis 70:406-414
Park, Meyeon; Vittinghoff, Eric; Ganz, Peter et al. (2014) Role of soluble endothelial cell-selective adhesion molecule biomarker in albuminuria and kidney function changes in patients with coronary artery disease: the Heart and Soul Study. Arterioscler Thromb Vasc Biol 34:231-6
Shlipak, Michael G; Mattes, Monica D; Peralta, Carmen A (2013) Update on cystatin C: incorporation into clinical practice. Am J Kidney Dis 62:595-603
Shlipak, Michael G; Day, Erica C (2013) Biomarkers for incident CKD: a new framework for interpreting the literature. Nat Rev Nephrol 9:478-83