Cis-vaccenic acid and the Framingham risk score predict chronic kidney disease: The multi-ethnic study of atherosclerosis (MESA)

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Abstract

Introduction

Data on the associations of fatty acids with chronic kidney disease (CKD) are sparse.

Materials and methods

We performed a cross-sectional study of 2792 men and women from the MESA cohort of African–American, Caucasian, Chinese and Hispanic adults without known cardiovascular disease. Plasma phospholipid fatty acid proportions were associated with estimated glomerular filtration rate (eGFR) and the albumin/creatinine ratio.

Results

Cis-vaccenic acid (18:1n−7), adjusted for other fatty acids using multivariate logistic regression (CI: 1.0–1.4), and step-wise logistic regression (CI: 1.02–1.42), was positively associated with reduced eGFR. The Framingham Risk Score, when adjusting for fatty acid proportions and demographic factors, was positively associated with CKD as measured by the eGFR and the albumin/creatinine ratio.

Discussion and conclusions

Plasma phospholipid proportions of the 18 carbon monounsaturated cis-vaccenic acid {18:1n−7}) and the Framingham Risk Score are associated with kidney function. The potential role of 18:1n−7 in the development of CKD warrants further investigation.

Introduction

Chronic kidney disease (CKD) is reaching epidemic proportions worldwide [1], [2]. The National Kidney Foundation's Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) published criteria for defining and staging CKD in 2002 [3]. Stages 3, 4 and 5 represent significant kidney impairment encompassing Glomerular Filtration Rate (GFR) of 30–59 ml/min, 15–29 ml/min, and less than 15 ml/min or dialysis dependence, respectively. An estimated fifteen and a half million Americans (7.7% of the population) are afflicted with stage 3 CKD, and 700,000 (0.35%) with stage 4 [4]. The number of patients with end-stage CKD or receiving dialysis for end stage CKD was approximately 540,373 adult patients in 2008 [5]. CKD remains an important risk factor for cardiovascular disease and individuals with CKD should be targeted with aggressive prevention measures [6].

Given the overlap between cardiovascular disease and CKD risk, these data support the need to investigate the ability of fatty acid models to predict prevalent and incident CKD. Although lipoproteins have been associated with CKD, the role of fatty acids has not been established [7], [8]. One recent study of elderly Italians demonstrated that a higher level of plasma unsaturated fatty acids predicted a less steep decline in GFR [9]. Similar data for younger individuals have been lacking. Due to the fact that many fatty acids are determined primarily by diet, lifestyle modification may have implications for public health strategies for the prevention of CKD. Using a cross-sectional study design, we investigated the association between plasma phospholipid fatty acids and CKD in a relatively young population within the Multi-Ethnic Study of Atherosclerosis. We hypothesized that plasma phospholipid fatty acid proportions, in a model created de novo within the MESA dataset, are associated with CKD as defined by either the estimated GFR (eGFR) <60 ml/min/1.73 m2 or a spot albumin/creatinine ratio ≥30 mg/g, which defines microalbuminuria.

Section snippets

Study participants

MESA is a prospective, population-based study designed to investigate the prevalence, risk factors, and progression of subclinical cardiovascular disease in a multi-ethnic cohort in the United States [10], [11]. Its study design and methods have been described [10]. Between July 2000 and July 2002, 6814 participants aged 45–84 years were recruited from 6 U.S. communities: Forsyth County, NC; New York, NY; Baltimore, MD; St. Paul, MN; Chicago, IL; and Los Angeles, CA. By taking into account the

Results

Characteristics of enrolled participants are displayed in Table 1. A person with a calculated eGFR <60 ml/min/1.73 m2 was categorized as a “CKD participant” and someone with an eGFR ≥60 ml/min/1.73 m2 as a “non-CKD participant”. The majority of individuals were over the age of 60, female, non-Caucasian, and overweight. The average age was higher for the CKD participants than the non-CKD participants and more CKD participants than non-CKD participants were female and Caucasian. Although body mass

Discussion

While there are established relationships between fatty acids and cardiovascular disease [25], [26], the role of fatty acids in the development of human CKD has not been clearly established [7], [8], [27]. While risk is generally straightforward for less complicated CVD, the presence of renal disease complicates risk so that usual risk factors are not consistently predictive of CVD. In the other hand, because their concentrations are established by multiple factors including nutritional status,

Acknowledgements

We thank the other investigators, staff and participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at: http://www.mesa-nhlbi.org.

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    Sources of Support. This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. This publication was also made possible by Grant Number KL2 RR 024136 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov/. Information on Re-engineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp. Additional resources were provided by R01 HL071933 (S.G.), Reliant Pharmaceuticals and by NIH Grant (P20 RR016479) from the INBRE Program of the National Center for Research Resources.

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