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      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)

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          Abstract

          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 m 2.

          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.

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          Most cited references25

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          Inflammatory markers and the risk of coronary heart disease in men and women.

          Few studies have simultaneously investigated the role of soluble tumor necrosis factor alpha (TNF-alpha) receptors types 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein, and interleukin-6 as predictors of cardiovascular events. The value of these inflammatory markers as independent predictors remains controversial. We examined plasma levels of sTNF-R1, sTNF-R2, interleukin-6, and C-reactive protein as markers of risk for coronary heart disease among women participating in the Nurses' Health Study and men participating in the Health Professionals Follow-up Study in nested case-control analyses. Among participants who provided a blood sample and who were free of cardiovascular disease at baseline, 239 women and 265 men had a nonfatal myocardial infarction or fatal coronary heart disease during eight years and six years of follow-up, respectively. Using risk-set sampling, we selected controls in a 2:1 ratio with matching for age, smoking status, and date of blood sampling. After adjustment for matching factors, high levels of interleukin-6 and C-reactive protein were significantly related to an increased risk of coronary heart disease in both sexes, whereas high levels of soluble TNF-alpha receptors were significant only among women. Further adjustment for lipid and nonlipid factors attenuated all associations; only C-reactive protein levels remained significant. The relative risk among all participants was 1.79 for those with C-reactive protein levels of at least 3.0 mg per liter, as compared with those with levels of less than 1.0 mg per liter (95 percent confidence interval, 1.27 to 2.51; P for trend <0.001). Additional adjustment for the presence or absence of diabetes and hypertension moderately attenuated the relative risk to 1.68 (95 percent confidence interval, 1.18 to 2.38; P for trend = 0.008). Elevated levels of inflammatory markers, particularly C-reactive protein, indicate an increased risk of coronary heart disease. Although plasma lipid levels were more strongly associated with an increased risk than were inflammatory markers, the level of C-reactive protein remained a significant contributor to the prediction of coronary heart disease. Copyright 2004 Massachusetts Medical Society.
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            Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease.

            The National Kidney Foundation has advocated the use of the abbreviated Modification of Diet in Renal Disease (MDRD) equation to estimate glomerular filtration rate (GFR) from serum creatinine measurements in clinical laboratories. However, healthy persons were not included in the development of the MDRD equation. To assess the accuracy of the MDRD equation in patients with chronic kidney disease compared with healthy persons and to develop a new equation that uses both patients with chronic kidney disease and healthy persons. Cross-sectional study. The Mayo Clinic, a tertiary-care medical center. Consecutive patients (n = 320) who had an iothalamate clearance test specifically for chronic kidney disease evaluation and consecutive healthy persons (n = 580) who had an iothalamate clearance test specifically for kidney donor evaluation. Serum creatinine levels, GFR, demographic characteristics, and clinical characteristics were abstracted from the medical record. The MDRD equation underestimated GFR by 6.2% in patients with chronic kidney disease and by 29% in healthy persons. Re-estimated coefficients for serum creatinine and sex were similar to the original MDRD equation in the chronic kidney disease series but not in the healthy series. At the same serum creatinine level, age, and sex, GFR was on average 26% higher in healthy persons than in patients with chronic kidney disease (P < 0.001). A quadratic GFR equation was developed to estimate logarithmic GFR from the following covariates: 1/SCr, 1/SCr2, age, and sex (where SCr = serum creatinine). The new equation was not developed in a general population sample. Elderly and African-American persons were underrepresented. The MDRD equation systematically underestimates GFR in healthy persons. A new equation developed with patients who have chronic kidney disease and healthy persons may be a step toward accurately estimating GFR when the diagnosis of chronic kidney disease is unknown.
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              Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency.

              Renal insufficiency has been associated with cardiovascular disease events and mortality in several prospective studies, but the mechanisms for the elevated risk are not clear. Little is known about the association of renal insufficiency with inflammatory and procoagulant markers, which are potential mediators for the cardiovascular risk of kidney disease. The cross-sectional association of renal insufficiency with 8 inflammatory and procoagulant factors was evaluated using baseline data from the Cardiovascular Health Study, a population-based cohort study of 5888 subjects aged > or =65 years. C-reactive protein, fibrinogen, factor VIIc, and factor VIIIc levels were measured in nearly all participants; interleukin-6, intercellular adhesion molecule-1, plasmin-antiplasmin complex, and D-dimer levels were measured in nearly half of participants. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. Multivariate linear regression was used to compare adjusted mean levels of each biomarker in persons with and without renal insufficiency after adjustment for other baseline characteristics. Renal insufficiency was present in 647 (11%) of Cardiovascular Health Study participants. After adjustment for baseline differences, levels of C-reactive protein, fibrinogen, interleukin-6, factor VIIc, factor VIIIc, plasmin-antiplasmin complex, and D-dimer were significantly greater among persons with renal insufficiency (P<0.001). In participants with clinical, subclinical, and no cardiovascular disease at baseline, the positive associations of renal insufficiency with these inflammatory and procoagulant markers were similar. Renal insufficiency was independently associated with elevations in inflammatory and procoagulant biomarkers. These pathways may be important mediators leading to the increased cardiovascular risk of persons with kidney disease.
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                Author and article information

                Journal
                BMC Nephrol
                BMC Nephrology
                BioMed Central
                1471-2369
                2008
                5 August 2008
                : 9
                : 9
                Affiliations
                [1 ]Department of Medicine, University of California San Francisco, San Francisco, CA, USA
                [2 ]San Francisco Veterans Affairs Medical Center, General Internal Medicine Section, San Francisco, CA, USA
                [3 ]Collaborative Health Studies Coordinating Center, University of Washington, Seattle, WA, USA
                [4 ]Departments of Medicine and Pathology, University of Vermont, Burlington, VT, USA
                [5 ]Renal Section, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA
                Article
                1471-2369-9-9
                10.1186/1471-2369-9-9
                2533297
                18681974
                76a9bdee-5b72-4720-af14-da7bb721c041
                Copyright © 2008 Keller et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 March 2008
                : 5 August 2008
                Categories
                Research Article

                Nephrology
                Nephrology

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