Elsevier

Cytokine

Volume 37, Issue 1, January 2007, Pages 1-5
Cytokine

Plasma and urine levels of resistin and adiponectin in chronic kidney disease

https://doi.org/10.1016/j.cyto.2007.02.003Get rights and content

Abstract

Background: Subjects with chronic kidney disease (CKD) have an increased risk of developing coronary atherosclerosis. Adipocyte hormones, resistin and adiponectin are implicated in insulin resistance and atherosclerosis. However, few studies in the literature address the role of adipocyte hormones in CKD. The aim of this study was to compare the levels of resistin, adiponectin and other inflammatory markers in subjects with CKD with those of the control subjects. Materials and methods: In a cross-sectional study, we measured basal metabolic panel, fasting lipid panel and levels of glucose, resistin, adiponectin, insulin, C-reactive protein (CRP) and TNF-α in 43 subjects with CKD compared with those of 34 control subjects. We also measured the resistin and adiponectin levels in urine samples (16). Results: Subjects with CKD have increased insulin levels and insulin resistance index (IRI). Compared with controls, subjects with CKD had increased levels of resistin (5.12 ± 3.2 vs.7.5 ± 5.9; p < 0.05), CRP (1.7 ± 2.2 vs. 5.97 ± 6.0; p < 0.0005), and TNF-α (3.4 ± 2.0 vs. 5.2 ± 3.5; p < 0.005). Resistin levels correlate with CRP and TNF-α, even with BMI as a covariate. Although 60% of subjects with CKD have CAD, e plasma levels of adiponectin were not decreased in subjects with CKD compared with controls (17.02 ± 9.8 vs. 16.40 ± 9.0 with p value 0.78). Urinary adiponectin levels correlate inversely with GFR (r = −0.4; p < 0.05) and plasma adiponectin levels (r = 0.9; p < 0.0001). Conclusions: Subjects with CKD had normal levels of plasma adiponectin despite the adverse metabolic environment for CAD. In addition, 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, suggesting that adiponectin clearance may be decreased as shown by the inverse correlation of urinary adiponectin with GFR.

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.

Section snippets

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.).

References (44)

  • R. Feinstein

    Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates

    J Biol Chem

    (1993)
  • A.S. Levey

    National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification

    Ann Intern Med

    (2003)
  • D.W. Cockcroft et al.

    Prediction of creatinine clearance from serum creatinine

    Nephron

    (1976)
  • A.S. Levey

    A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group

    Ann Intern Med

    (1999)
  • K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J...
  • M.J. Sarnak

    Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention

    Circulation

    (2003)
  • A.S. Go

    Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization

    N Engl J Med

    (2004)
  • D.E. Weiner

    Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies

    J Am Soc Nephrol

    (2004)
  • T. Shoji et al.

    Chronic kidney disease as a metabolic syndrome with malnutrition---need for strict control of risk factors

    Intern Med

    (2005)
  • K. Asayama

    Decrease in serum adiponectin level due to obesity and visceral fat accumulation in children

    Obes Res

    (2003)
  • M. Matsubara et al.

    Decreased plasma adiponectin concentrations in women with dyslipidemia

    J Clin Endocrinol Metab

    (2002)
  • K. Hotta

    Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients

    Arterioscler Thromb Vasc Biol

    (2000)
  • Cited by (51)

    • Circulating secreted frizzled-related protein 5 and chronic kidney disease in patients with acute ST-segment elevation myocardial infarction

      2018, Cytokine
      Citation Excerpt :

      In addition, adiponectin has also been reports to have anti-inflammatory properties [32,33] and to be inversely associated with obesity, coronary artery disease, and type 2 diabetes [32,34,35]. In contrast to these findings, prior studies of adiponectin and CKD have shown either higher adiponectin levels in patients with CKD compared to those without CKD [36] or no difference in adiponectin levels between the two groups in unadjusted analyses [37,38]. In the present study, we observed significant differences in the median values of Sfrp5 between the patients with and without CKD.

    • Serum adiponectin levels in renal transplant recipients with and without metabolic syndrome

      2012, Transplantation Proceedings
      Citation Excerpt :

      We demonstrated an inverse correlation between eGFR and serum APN level (Fig 1). This finding is consistent with the findings of previous reports,8 suggesting that renal clearance of APN may affect APN serum levels. However, the increased serum level of APN in patients with CKD may also be a response to myocardial dysfunction as shown by the increase of APN level in response to the infusion of atrial natriuretic peptide.9

    View all citing articles on Scopus
    View full text