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Risk factor profile for chronic kidney disease is similar to risk factor profile for small artery disease

Turner, Stephen T.a,c; Rule, Andrew D.a,c; Schwartz, Gary L.a,c; Kullo, Iftikhar J.b,c; Mosley, Thomas H.f; Jack, Clifford R.d; Kardia, Sharon L.R.g; Boerwinkle, Erich; Bailey, Kent R.e

doi: 10.1097/HJH.0b013e328349052b
Original papers: Kidney

Background and method: We investigated whether chronic kidney disease detected by increased serum creatinine (SCr) or urine albumin-to-creatinine ratio (UACR) may reflect arteriosclerosis involving the kidneys. The sample consisted of 1585 members of sibships (804 non-Hispanic whites and 781 non-Hispanic blacks) in which at least two siblings had primary hypertension. We first evaluated the correlations of increased SCr and UACR with the presence of cerebral small vessel arteriosclerosis, which was determined by increased subcortical white matter hyperintensity (WMH) volume on brain magnetic resonance imaging; and with peripheral large vessel arteriosclerosis, which was determined by decreased ankle-brachial index (ABI). After age adjustment, increased SCr and UACR correlated with increased WMH volume (0.54 and 0.52, respectively) and with decreased ABI (0.50 and 0.54, respectively; all P < 0.001). We then used logistic regression to evaluate the dependency of each measure of disease on conventional risk factors for arteriosclerosis to assess whether the risk factors’ effects were proportional across different measures of disease.

Results: Age, race, sex, hypertension, diabetes, total cholesterol, and smoking made similar overall contributions to the prediction of each measure of disease, as judged by the model C-statistics, which varied in a narrow range from 0.84 to 0.85 (all P < 0.001). However, the relative contributions that the modifiable risk factors, including hypertension, diabetes, total cholesterol, and smoking made to prediction of increased SCr and UACR were disproportionate to their relative contributions to prediction of decreased ABI (P < 0.0001).

Conclusion: The findings support the view that chronic kidney disease detected by increased SCr or UACR primarily reflects small vessel arteriosclerosis involving the kidneys.

aDivision of Nephrology and Hypertension

bDivision of Cardiovascular Diseases

cDepartment of Internal Medicine

dDepartment of Diagnostic Radiology

eDivision of Biostatistics, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota

fDepartment of Medicine, University of Mississippi Medical Center, Jackson, Mississippi

gDepartment of Epidemiology, University of Michigan, Ann Arbor, Michigan

hHuman Genetics Center and Institute of Molecular Medicine, University of Texas-Houston Health Science Center, Houston, Texas, USA

Correspondence to Stephen T. Turner, MD, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA Tel: +1 507 284 8129; fax: +1 507 266 1702; e-mail:

Abbreviations: ABI, ankle-brachial index; CKD, chronic kidney disease; CKD-EPI, chronic kidney disease epidemiology; HDL, high-density lipoprotein; SCr, serum creatinine; UACR, urine albumin-to-creatinine ratio

Received 5 February, 2011

Revised 6 April, 2011

Accepted 20 May, 2011

© 2011 Lippincott Williams & Wilkins, Inc.