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Lipoprotein Abnormalities Associated with Mild Impairment of Kidney Function in the Multi-Ethnic Study of Atherosclerosis

Ian H. de Boer^*, Brad C. Astor, Holly Kramer, Walter Palmas, Stephen L. Seliger^||, Michael G. Shlipak^¶, David S. Siscovick^**, Michael Y. Tsai, and Bryan Kestenbaum^*

^* Division of Nephrology and ^** Cardiovascular Health Research Unit, University of Washington, Seattle, Washington; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Preventive Medicine, Loyola University, Maywood, Illinois; Department of Medicine, Columbia University, New York, New York; ^|| Division of Nephrology, University of Maryland, Baltimore, Maryland; ^¶ Department of Medicine, University of California, San Francisco, San Francisco, California; and Laboratory Medical Pathology, University of Minnesota, Minneapolis, Minnesota

Correspondence: Dr. Ian H. de Boer, University of Washington, Division of Nephrology, Box 356521, BB-1265 Health Sciences Building, 1959 NE Pacific, Seattle, WA 98195. Phone: 206-543-3792; Fax: 206-685-6881; E-mail: deboer{at}u.washington.edu

Background and objectives: Impaired kidney function is associated with increased risk for cardiovascular disease and may progress over time to end-stage renal disease. Abnormal lipoprotein metabolism has been implicated as a possible cause of these complications, but lipoproteins have not been described at the earliest stages of kidney disease.

Design, setting, participants, & measurements: This study examined cross-sectional associations of serum cystatin C with conventional lipid measurements and detailed nuclear magnetic resonance lipoprotein measurements in the community-based Multi-Ethnic Study of Atherosclerosis. A total of 5109 participants with estimated glomerular filtration rate 60 ml/min per 1.73 m² were included in analyses.

Results: Adjusting for age, gender, race/ethnicity, diabetes, impaired fasting glucose, BP, smoking, medications, body mass index, and albuminuria, greater cystatin C concentrations were associated with progressively unfavorable lipid and lipoprotein concentrations, including greater triglyceride concentration (+22 mg/dl, comparing fifth versus first quintiles of cystatin C) and lesser high-density lipoprotein cholesterol concentration (–7 mg/dl) but not with low-density lipoprotein cholesterol measured using conventional methods. When low-density lipoprotein particle subclasses were examined in more detail using nuclear magnetic resonance, greater cystatin C was associated with greater concentrations of atherogenic small low-density lipoprotein particles (+63 nmol/L) and intermediate-density lipoprotein particles (+6 nmol/L) and with a decrease in mean low-density lipoprotein particle size.

Conclusions: Lipoprotein abnormalities are present with milder degrees of renal impairment than previously recognized, and abnormalities in low-density lipoprotein particle distribution may not be appreciated using conventional lipid measurements. These abnormalities may contribute to kidney disease progression and/or cardiovascular disease.