Inflammation, hemostasis, and the risk of kidney function decline in the Atherosclerosis Risk in Communities (ARIC) Study.
BACKGROUND
Inflammation and hemostasis may increase the risk of kidney function decline; however, data from prospective studies are sparse.


METHODS
The Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational cohort.


METHODS
We used data from 14,854 middle-aged adults from 4 different US communities.


METHODS
Markers of inflammation and hemostasis were examined.


METHODS
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.


CONCLUSIONS
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.
Bash
Lori D
LD
Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21201, USA. lbash@jhsph.edu
Erlinger
Thomas P
TP
Coresh
Josef
J
Marsh-Manzi
Jane
J
Folsom
Aaron R
AR
Astor
Brad C
BC
D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications* / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood* / Q000453:epidemiology* / Q000503:physiopathology; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D014481:United States; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D012709:Serum Albumin; D014841:von Willebrand Factor; D005169:Factor VIII; D005340:Fibrinogen; D003404:Creatinine