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(Stroke. 2007;38:3121.)
© 2007 American Heart Association, Inc.

Original Contributions

Chronic Kidney Disease Is Associated With White Matter Hyperintensity Volume

The Northern Manhattan Study (NOMAS)

Minesh Khatri, BS; Clinton B. Wright, MD, MS; Thomas L. Nickolas, MD, MS; Mitsuhiro Yoshita, MD, PhD; Myunghee C. Paik, PhD; Grace Kranwinkel, MD; Ralph L. Sacco, MD, MS Charles DeCarli, MD

From the Division of Stroke and Critical Care, Department of Neurology (C.B.W., G.K.), and the Division of Nephrology, Department of Medicine (T.L.N.), College of Physicians and Surgeons of Columbia University, New York, NY; the Departments of Biostatistics (M.C.P.), Mailman School of Public Health, Columbia University, New York, NY; the Department of Neurology and Center for Neuroscience (C.D.), University of California–Davis, Sacramento, Calif; Duke University School of Medicine (M.K.), Durham, NC; and the Department of Neurology (R.L.S.), Miller School of Medicine, University of Miami, Miami, Fla.

Correspondence to Clinton B. Wright, MD, MS, Division of Stroke and Critical Care, College of Physicians and Surgeons of Columbia University, NI-Room 640, 710 W 168th Street, New York, NY 10032. E-mail cbw7{at}columbia.edu

Background and Purpose— White matter hyperintensities have been associated with increased risk of stroke, cognitive decline, and dementia. Chronic kidney disease is a risk factor for vascular disease and has been associated with inflammation and endothelial dysfunction, which have been implicated in the pathogenesis of white matter hyperintensities. Few studies have explored the relationship between chronic kidney disease and white matter hyperintensities.

Methods— The Northern Manhattan Study is a prospective, community-based cohort of which a subset of stroke-free participants underwent MRIs. MRIs were analyzed quantitatively for white matter hyperintensities volume, which was log-transformed to yield a normal distribution (log-white matter hyperintensity volume). Kidney function was modeled using serum creatinine, the Cockcroft-Gault formula for creatinine clearance, and the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate. Creatinine clearance and estimated glomerular filtration rate were trichotomized to 15 to 60 mL/min, 60 to 90 mL/min, and >90 mL/min (reference). Linear regression was used to measure the association between kidney function and log-white matter hyperintensity volume adjusting for age, gender, race–ethnicity, education, cardiac disease, diabetes, homocysteine, and hypertension.

Results— Baseline data were available on 615 subjects (mean age 70 years, 60% women, 18% whites, 21% blacks, 62% Hispanics). In multivariate analysis, creatinine clearance 15 to 60 mL/min was associated with increased log-white matter hyperintensity volume (ß 0.322; 95% CI, 0.095 to 0.550) as was estimated glomerular filtration rate 15 to 60 mL/min (ß 0.322; 95% CI, 0.080 to 0.564). Serum creatinine, per 1-mg/dL increase, was also positively associated with log-white matter hyperintensity volume (ß 1.479; 95% CI, 1.067 to 2.050).

Conclusions— The association between moderate–severe chronic kidney disease and white matter hyperintensity volume highlights the growing importance of kidney disease as a possible determinant of cerebrovascular disease and/or as a marker of microangiopathy.

Key Words: chronic • kidney failure • leukoaraiosis • magnetic resonance imaging

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