Original article
Serum visfatin as a non-traditional biomarker of endothelial dysfunction in chronic kidney disease: An Egyptian study

https://doi.org/10.1016/j.ejim.2010.09.011Get rights and content

Abstract

Background

Endothelial dysfunction (ED) is closely linked to cardiovascular disease and outcome in patients with chronic kidney disease (CKD). Visfatin is an adipocytokine that recently generated much interest; however, its role in CKD remains to be clarified. This study aimed to assess visfatin in correlation with markers of ED and inflammation in Egyptian patients with CKD.

Methods

The study included 40 non-diabetic, clinically stable CKD patients and 20 healthy volunteers. Serum levels of visfatin, markers of ED (intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) and markers of inflammation (interleukin-6 (IL-6), and C-reactive protein (CRP)) were measured. Endothelial function was evaluated using brachial artery flow-mediated dilatation (FMD).

Results

Serum visfatin, ICAM-1, VCAM-1, CRP, and IL-6 levels were significantly elevated and FMD% was decreased in CKD patients as compared to controls. Visfatin correlated positively with ICAM-1, VCAM-1, CRP, and IL-6 and negatively with FMD% in CKD patients. In a multiple regression model, visfatin was strongly and independently associated with FMD (Beta = −0.02, P < 0.001) in CKD patients.

Conclusions

Serum visfatin is strongly associated with endothelial adhesion molecules and FMD%, suggesting that visfatin is an important promising biomarker for prediction of ED and future cardiovascular risk in CKD patients. Moreover, the relationship between visfatin and IL-6 indicates that circulating visfatin may reflect the sub-clinical inflammatory status. Thus, visfatin might be involved in the complex interactions between ED, inflammation, and atherosclerosis and their major clinical consequences; however, further prospective studies are required to prove this hypothesis.

Introduction

Cardiovascular disease (CVD) is a major contributor to the morbidity and mortality in patients with chronic kidney disease (CKD) [1]. As traditional risk factors cannot explain the high prevalence of CVD in this population, non-traditional factors are taken into account, such as inflammation, insulin resistance, oxidative stress and endothelial dysfunction [2]. Endothelial dysfunction (ED) represents an obligatory, prodromal phase in the atherosclerotic process. It has been implicated in the pathophysiology of different forms of CVD, including chronic heart failure, diabetes mellitus, hypertension, coronary heart disease and CKD [3], [4]. The etiology of ED is complex and involves dysregulation of multiple pathways [4].

Adipose tissue is now known to be a complex organ with pleiotropic functions far beyond the mere storage of energy. Indeed, it has recently been shown that fat tissue secretes a number of adipocytokines, including leptin, adiponectin, resistin and visfatin, as well as proinflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 [5]. It plays an important role in the catabolic uremic milieu, and has been linked to systemic inflammation and uremic anorexia [6], [7], [8]. In recent years, a cross-talk between the adipose tissue and the endothelium has been discovered and the issue is being intensively investigated.

Visfatin, also known as pre-B cell colony-enhancing factor 1(PBEF-1) or nicotinamide phosphoribosyltransferase (Nampt), is a ubiquitous adipokine first described by Fukuhara et al. [9] in 2005. It is produced by adipose tissue, skeletal muscle, bone marrow, the liver, lymphocytes and mesangial cells. However, the pathophysiological role of visfatin in the kidney is not completely understood [10]. Recently, visfatin was shown to be associated with flow-mediated dilatation, a surrogate marker of ED in diabetic patients [11]. This link appears to be of particular relevance in patients with CKD, because reduced glomerular filtration rate can contribute to the accumulation of this adipokine.

The aim of the present study was to assess the clinical significance of serum visfatin and to evaluate its possible correlation with markers of ED and inflammation in Egyptian patients with CKD.

Section snippets

Subjects

This study was performed on sixty subjects. Forty clinically stable chronic kidney disease patients on conservative treatment (23 males and 17 females) with a mean age (± SD) of 47.2 ± 11.1 years were selected from those attending the Internal Medicine Department in Tanta University Hospital. All patients were diagnosed as having CKD according to their estimated glomerular filtration rate and the presence of kidney injury as defined by National Kidney Foundation K/DOQI Guidelines [12]. Patients

Results

The main clinical and biochemical data of the patients with chronic kidney disease are presented in Table 1. There were no statistically significant differences between patients and controls regarding age, BMI, total cholesterol and LDL-cholesterol levels. The triglycerides were higher (p < 0.01) and HDL-cholesterol, and serum albumin levels were significantly lower (p < 0.001) in CKD patients than those of the controls (Table 1).

Serum visfatin, ICAM-1 and VCAM-1 levels were higher in CKD patients

Discussion

The lifespan of patients with CKD is markedly reduced due to premature cardiovascular death in more than 50% of this population; however, the conventional risk factors cannot explain the extraordinary increase in morbidity and mortality among CKD patients [22]. Indeed, chronic renal disease is a highly atherogenic disease and state of sub-clinical systemic inflammation involving cytokines derived from adipose tissue-adipocytokines. Deteriorating renal function may increase overall inflammatory

Learning points

  • •

    Serum visfatin can be considered as a promising biomarker for prediction of ED in CKD, that can allow the early identification of patients at higher risk of developing future CVD.

  • •

    Further research is still needed to clarify the potential influence of different adipocytokines on the endothelial health and vascular outcome in CKD.

  • •

    Visfatin might represent interesting novel drug target to reduce atherosclerotic CVD risk in patients with CKD, but its potential therapeutic possibility cannot be

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