Plasma and urine levels of resistin and adiponectin in chronic kidney disease
Introduction
Chronic kidney disease (CKD) is a major public health problem. Around 20 million adults in the United States have CKD, 8 million of whom are classified as having moderate or severe kidney disease [1]. Glomerular filtration rate (GFR), the best measure of overall kidney function in health and disease, can be estimated from serum creatinine levels using prediction equations such as the Cockcroft–Gault equation [2] and the MDRD study equation [3]. A GFR level less than 60 mL/min/1.73 m2 represents a loss of 50% or more of normal kidney function in adults. The level of kidney function, regardless of diagnosis, determines the stage of CKD [4]. Recent studies show that even mild renal dysfunction is associated with an increased risk of cardiovascular disease (CVD) [5], [6]. Patients with CKD have risk increased for morbidity and mortality from CVD and considered as potential candidates for aggressive risk factor reduction [7]. Their multiple metabolic abnormalities, such as hypertension, insulin resistance, and dyslipidemia, along with other CKD-related risk factors, may accelerate atherosclerosis [8].
In cross-sectional studies, plasma adiponectin levels are inversely correlated with obesity [9], [10], dyslipidemia [11], coronary artery disease [12], insulin resistance [13], [14], waist-to-hip ratio [14], and increased levels of CRP and IL-6 [15], two inflammatory mediators and markers of increased cardiovascular risk. Resistin has been shown to promote endothelial cell activation and has been linked to cardiovascular disease in the metabolic syndrome [16]. Circulating levels of resistin are proportional to the degree of adiposity [17], more so with abdominal adiposity [18], with multifold expression in visceral adipocytes [19]. Adipose tissue also synthesizes and secretes TNF-α, IL-6, and other cytokines. Increased synthesis of these cytokines in obese subjects leads to insulin resistance in muscle [20], increased synthesis of acute-phase reactants in the liver (CRP and fibrinogen), or activation of macrophages in atheromatous plaques [21]. Both total and abdominal adiposity were strongly associated with significant increased levels of CRP and IL-6 [22]. Resistin appears to be a pro-inflammatory cytokine.
This study evaluated the relation of plasma adiponectin and resistin to GFR, body mass index (BMI), insulin resistance and inflammatory markers, C-reactive protein (CRP) and tumor necrosis factor α (TNF-α) in subjects with CKD stages 3 and 4.
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Materials and methods
This is a cross-sectional study was carried out following after an institutional review board approval. The study subjects included 43 subjects with CKD and 34 control subjects with normal kidney function. Clinical data obtained from subjects at clinic visits is shown in Table 1. These include blood pressure, height, weight, BMI, measurement of waist circumference, smoking, alcohol use and family history of diabetes. Blood samples were obtained after an overnight fast (∼10 h). Basal metabolic
Statistical methods
The primary purpose of this study was to correlate the serum levels of resistin and adiponectin with insulin resistance and to compare the levels of resistin and adiponectin in subjects with CKD with those of control subjects. The results are expressed as the means ± SD unless otherwise stated. Comparisons of the mean differences in the biochemical parameters between the controls and subjects with CKD were performed using Student’s t-test. The relationships between resistin and adiponectin with
Results
Demographic characteristics of the study population are presented in Table 1. Subjects with CKD tended to be older and most of them had hypertension compared with the control subjects. It would have eliminated the age as a confounding factor if the subjects with CKD were age matched. Biochemical data in subjects with CKD compared with the control subjects with normal kidney function was shown in Table 2. The mean GFR of subjects with CKD was 29.1 ± 7.1 (SD) mL/min/1.73 m2. Glomerular filtration
Discussion
There are several interesting findings in our study. Although 60% of subjects with CKD have CAD (compared with the 35% in literature [23], we found no decrease in adiponectin levels. In our past studies, we noted decreased adiponectin levels in subjects with prediabetes and diabetes and in subjects with CAD with normal kidney function [24]. Our adiponectin results are similar in that they did not decrease in patients with CKD and CAD [25], [26], [27], but in contrast they are not increased as
Conclusions
This study demonstrates the relationship between resistin and TNF-α in subjects with CKD and suggests that resistin may play a role in the sub-clinical inflammation associated with CKD.
Acknowledgments
This work was supported by an Edward Stiles Grant from LSU Health Sciences Center (Y.S.) and a grant (RO1 DK064797) from NIDDK and the Office of Dietary Supplements of the National Institutes of Health (S.K.J.).
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