Association of Kidney Function With Inflammatory and Procoagulant Markers in a Diverse Cohort: A Cross-Sectional Analysis From the Multi-Ethnic Study of Atherosclerosis (MESA)

Christopher Keller; Ronit Katz; Mary Cushman; Linda F. Fried; Michael Shlipak


BMC Nephrology 

In This Article

Abstract and Background


Background. Prior studies using creatinine-based estimated glomerular filtration rate (eGFR) have found limited associations between kidney function and markers of inflammation. Using eGFR and cystatin C, a novel marker of kidney function, the authors investigated the association of kidney function with multiple biomarkers in a diverse cohort.
Methods. The Multi-Ethnic Study of Atherosclerosis consists of 6,814 participants of white, African-American, Hispanic, and Chinese descent, enrolled from 2000–2002 from six U.S. communities. Measurements at the enrollment visit included serum creatinine, cystatin C, and six inflammatory and procoagulant biomarkers. Creatinine-based eGFR was estimated using the four-variable Modification of Diet in Renal Disease equation, and chronic kidney disease was defined by an eGFR < 60 mL/min/1.73 m2.
Results. Adjusted partial correlations between cystatin C and all biomarkers were statistically significant: C-reactive protein (r = 0.08), interleukin-6 (r = 0.16), tumor necrosis factor-α soluble receptor 1 (TNF-αR1; r = 0.75), intercellular adhesion molecule-1 (r = 0.21), fibrinogen (r = 0.14), and factor VIII (r = 0.11; two-sided p < 0.01 for all). In participants without chronic kidney disease, higher creatinine-based eGFR was associated only with higher TNF-αR1 levels.
Conclusion. In a cohort characterized by ethnic diversity, cystatin C was directly associated with multiple procoagulant and inflammatory markers. Creatinine-based eGFR had similar associations with these biomarkers among subjects with chronic kidney disease.


Higher levels of markers of inflammation, such as C-reactive protein (CRP) and interleukin 6 (IL-6), have been associated with cardiovascular disease in healthy populations.[1,2,3] In subjects with end stage renal disease (ESRD), inflammatory biomarkers are significantly elevated and predict poor outcomes.[4,5,6,7] In subjects with kidney disease not on hemodialysis, kidney function has been associated with markers of inflammation for creatinine-based estimated glomerular filtration rates (eGFR) below 60 mL/min/1.73 m2. Above that threshold, two studies did not find an association between eGFR and markers of inflammation.[8,9]

Cystatin C, a cysteine protease inhibitor secreted by all nucleated cells, is a novel serum marker for kidney disease that may better detect small changes in kidney function.[10,11,12] Since creatinine-based eGFR is not reliable above 60 mL/min/1.73 m2, cystatin C may be superior in detecting an association with inflammation in subjects with mild to moderate kidney disease.[13,14] Using cystatin C as a marker for kidney function in an ambulatory elderly cohort, all with creatinine-based eGFR ≥ 60, we reported linear associations between cystatin C and five inflammatory markers: CRP, IL-6, tumor necrosis factor alpha (TNF-α), and two soluble TNF-α receptors.[15] In a cohort with known coronary artery disease, cystatin C was associated with both CRP and fibrinogen across the entire cohort, while creatinine-based eGFR was significantly associated with CRP and fibrinogen only for eGFR < 60.[16]

The current study investigated the association of both creatinine-based eGFR and cystatin C with six inflammatory and procoagulant biomarkers in the Multi-Ethnic Study of Atherosclerosis (MESA), a large cohort characterized by racial and ethnic diversity. Compared with prior studies on kidney function and markers of inflammation, this study featured a population with four racial/ethnic groups, a younger mean age (62 years), no clinical cardiovascular disease, and more extensive measurements of both inflammatory and procoagulant biomarkers. In addition, a second objective of this study was to test whether the association between kidney function and multiple inflammatory and procoagulant biomarkers differed by race/ethnicity.


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