Inflammation, Hemostasis, and the Risk of Kidney Function Decline in the Atherosclerosis Risk in Communities (ARIC) Study

Lori D. Bash, Thomas P. Erlinger, Josef Coresh, Jane Marsh-Manzi, Aaron R. Folsom, Brad C. Astor

Research output: Contribution to journalArticle

Abstract

Background: Inflammation and hemostasis may increase the risk of kidney function decline; however, data from prospective studies are sparse. Study Design: The Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational cohort. Setting & Participants: We used data from 14,854 middle-aged adults from 4 different US communities. Predictor: Markers of inflammation and hemostasis were examined. Outcomes & Measurements: The risk of kidney function decrease associated with these markers was studied. Glomerular filtration rate (GFR) was calculated from serum creatinine levels using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Chronic kidney disease (CKD) was defined as: (1) a decrease in estimated GFR to less than 60 mL/min/1.73 m2 from greater than 60 mL/min/1.73 m2 at baseline, or (2) a hospitalization discharge or death coded for CKD. Serum creatinine was measured at baseline and the 3- and 9-year follow-up visits. Hazard ratios (HRs) of CKD associated with increased levels of inflammatory and hemostatic variables were estimated by using multivariate Cox proportional hazards regression. Results: 1,787 cases of CKD developed between 1987 and 2004. After adjusting for demographics, smoking, blood pressure, diabetes, lipid levels, prior myocardial infarction, antihypertensive use, alcohol use, year of marker measurement, and baseline renal function using estimated GFR, the risk of incident CKD increased with increasing quartiles of white blood cell count (HR quartile 4 versus quartile 1, 1.30; 95% confidence interval [CI], 1.12 to 1.50; P trend = 0.001), fibrinogen (HR, 1.25; 95% CI, 1.09 to 1.44; P <0.001), von Willebrand factor (HR, 1.46; 95% CI, 1.26 to 1.68; P <0.001), and factor VIIIc (HR, 1.39; 95% CI, 1.20 to 1.60; P <0.001). A strong inverse association was found between serum albumin level and risk of CKD (HR, 0.63; 95% CI, 0.55 to 0.72; P <0.001). No independent association was found with factor VIIc level. Limitations: Although we lacked a direct measure of kidney function, associations were robust to case definitions. Conclusions: Markers of inflammation and hemostasis are associated with greater risk of kidney function decrease. Findings suggest that inflammation and hemostasis are antecedent pathways for CKD.

Original languageEnglish (US)
Pages (from-to)596-605
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume53
Issue number4
DOIs
StatePublished - Apr 2009

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Hemostasis
Chronic Renal Insufficiency
Atherosclerosis
Inflammation
Kidney
Confidence Intervals
Glomerular Filtration Rate
Creatinine
Prospective Studies
Diet Therapy
von Willebrand Factor
Hemostatics
Serum
Leukocyte Count
Serum Albumin
Fibrinogen
Antihypertensive Agents
Hospitalization
Smoking
Myocardial Infarction

Keywords

  • Atherosclerosis Risk in Communities (ARIC)
  • chronic kidney disease
  • hemostasis
  • Inflammation
  • kidney

ASJC Scopus subject areas

  • Nephrology

Cite this

Inflammation, Hemostasis, and the Risk of Kidney Function Decline in the Atherosclerosis Risk in Communities (ARIC) Study. / Bash, Lori D.; Erlinger, Thomas P.; Coresh, Josef; Marsh-Manzi, Jane; Folsom, Aaron R.; Astor, Brad C.

In: American Journal of Kidney Diseases, Vol. 53, No. 4, 04.2009, p. 596-605.

Research output: Contribution to journalArticle

Bash, Lori D. ; Erlinger, Thomas P. ; Coresh, Josef ; Marsh-Manzi, Jane ; Folsom, Aaron R. ; Astor, Brad C. / Inflammation, Hemostasis, and the Risk of Kidney Function Decline in the Atherosclerosis Risk in Communities (ARIC) Study. In: American Journal of Kidney Diseases. 2009 ; Vol. 53, No. 4. pp. 596-605.
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abstract = "Background: Inflammation and hemostasis may increase the risk of kidney function decline; however, data from prospective studies are sparse. Study Design: The Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational cohort. Setting & Participants: We used data from 14,854 middle-aged adults from 4 different US communities. Predictor: Markers of inflammation and hemostasis were examined. Outcomes & Measurements: The risk of kidney function decrease associated with these markers was studied. Glomerular filtration rate (GFR) was calculated from serum creatinine levels using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Chronic kidney disease (CKD) was defined as: (1) a decrease in estimated GFR to less than 60 mL/min/1.73 m2 from greater than 60 mL/min/1.73 m2 at baseline, or (2) a hospitalization discharge or death coded for CKD. Serum creatinine was measured at baseline and the 3- and 9-year follow-up visits. Hazard ratios (HRs) of CKD associated with increased levels of inflammatory and hemostatic variables were estimated by using multivariate Cox proportional hazards regression. Results: 1,787 cases of CKD developed between 1987 and 2004. After adjusting for demographics, smoking, blood pressure, diabetes, lipid levels, prior myocardial infarction, antihypertensive use, alcohol use, year of marker measurement, and baseline renal function using estimated GFR, the risk of incident CKD increased with increasing quartiles of white blood cell count (HR quartile 4 versus quartile 1, 1.30; 95{\%} confidence interval [CI], 1.12 to 1.50; P trend = 0.001), fibrinogen (HR, 1.25; 95{\%} CI, 1.09 to 1.44; P <0.001), von Willebrand factor (HR, 1.46; 95{\%} CI, 1.26 to 1.68; P <0.001), and factor VIIIc (HR, 1.39; 95{\%} CI, 1.20 to 1.60; P <0.001). A strong inverse association was found between serum albumin level and risk of CKD (HR, 0.63; 95{\%} CI, 0.55 to 0.72; P <0.001). No independent association was found with factor VIIc level. Limitations: Although we lacked a direct measure of kidney function, associations were robust to case definitions. Conclusions: Markers of inflammation and hemostasis are associated with greater risk of kidney function decrease. Findings suggest that inflammation and hemostasis are antecedent pathways for CKD.",
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AU - Bash, Lori D.

AU - Erlinger, Thomas P.

AU - Coresh, Josef

AU - Marsh-Manzi, Jane

AU - Folsom, Aaron R.

AU - Astor, Brad C.

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N2 - Background: Inflammation and hemostasis may increase the risk of kidney function decline; however, data from prospective studies are sparse. Study Design: The Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational cohort. Setting & Participants: We used data from 14,854 middle-aged adults from 4 different US communities. Predictor: Markers of inflammation and hemostasis were examined. Outcomes & Measurements: The risk of kidney function decrease associated with these markers was studied. Glomerular filtration rate (GFR) was calculated from serum creatinine levels using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Chronic kidney disease (CKD) was defined as: (1) a decrease in estimated GFR to less than 60 mL/min/1.73 m2 from greater than 60 mL/min/1.73 m2 at baseline, or (2) a hospitalization discharge or death coded for CKD. Serum creatinine was measured at baseline and the 3- and 9-year follow-up visits. Hazard ratios (HRs) of CKD associated with increased levels of inflammatory and hemostatic variables were estimated by using multivariate Cox proportional hazards regression. Results: 1,787 cases of CKD developed between 1987 and 2004. After adjusting for demographics, smoking, blood pressure, diabetes, lipid levels, prior myocardial infarction, antihypertensive use, alcohol use, year of marker measurement, and baseline renal function using estimated GFR, the risk of incident CKD increased with increasing quartiles of white blood cell count (HR quartile 4 versus quartile 1, 1.30; 95% confidence interval [CI], 1.12 to 1.50; P trend = 0.001), fibrinogen (HR, 1.25; 95% CI, 1.09 to 1.44; P <0.001), von Willebrand factor (HR, 1.46; 95% CI, 1.26 to 1.68; P <0.001), and factor VIIIc (HR, 1.39; 95% CI, 1.20 to 1.60; P <0.001). A strong inverse association was found between serum albumin level and risk of CKD (HR, 0.63; 95% CI, 0.55 to 0.72; P <0.001). No independent association was found with factor VIIc level. Limitations: Although we lacked a direct measure of kidney function, associations were robust to case definitions. Conclusions: Markers of inflammation and hemostasis are associated with greater risk of kidney function decrease. Findings suggest that inflammation and hemostasis are antecedent pathways for CKD.

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