Oxidative stress, phosphate and creatinine levels are independently associated with vascular endothelial growth factor levels in patients with chronic renal failure
Introduction
Atherosclerosis and consequent cardiovascular disease (CVD) are recognized as leading reasons of the increased morbidity and mortality observed in patients with chronic renal failure (CRF). Accelerated atherosclerosis in this population appears to be caused by a synergism of different mechanisms, such as metabolic syndrome, anemia, inflammation, oxidative stress (SOX) and abnormal calcium and phosphate metabolism [1]. These non-traditional risk factors seem to appear early during the progression of kidney damage and probably are responsible for the large difference in cardiovascular mortality between patients with CRF and the general population [2].
Oxidative stress as well as inflammation are present in patients with CRF [3], [4], [5], [6], [7], and may contribute to enhanced cardiovascular complications in this population [1], [2]. On the other hand, atherosclerosis is also associated with increased expression of adhesion molecules, cytokines and growth factors—including vascular endothelial growth factor (VEGF), produced by cells participating in this process [8]. VEGF is a main regulator of blood vessel growth, it plays an important role in the maintenance of endothelial integrity and vascular permeability to serum proteins. Its level is increased in conditions associated with increased risk of vascular disease, for example in cardiac allografts atherosclerosis [9] or in patients with diabetic nephropathy [10]. However, controversy remains as to whether VEGF has vasoprotective [11] or atherosclerogenic effects [12]. Recently, Doi et al. [13] reported the contribution of VEGF to CRF progression, especially in males.
To our knowledge, there is only one report demonstrating elevated VEGF levels in non-diabetic predialysis uraemia [14] but the reasons for higher level of this growth factor in renal insufficiency are unknown. In our previous study, we have demonstrated the association between VEGF levels and oxidative stress in hemodialysis patients [15]. The aim of the present study was to determine VEGF levels across the whole range of renal function and the possible relationship between oxidative stress, inflammation and this growth factor level in uraemia.
Section snippets
Subjects
Fifty-five adult patients with CRF, who were clinically stable and free of active infection, and autoimmune diseases, participated in the study. None of the patients received immunosuppressive treatment, lipid-lowering agents, non-steroidal anti-inflammatory drugs or antioxidants such as vitamin E, C or allopurinol at the time of the study. End stage renal disease was attributed to glomerulonephritis in 22 cases, interstitial nephritis in 6, polycystic kidney disease in 9, hypertensive
Results
The demographic, biochemical and clinical characteristics of controls and CRF patients are shown in Table 1. There was no difference among CRF groups in age, BMI, total cholesterol, triglycerides, platelets, leukocytes, total protein, albumin, calcium, blood pressure and antihypertensive medication. Serum creatinine, urea, phosphate, and CaxP increased, as expected, whereas eGFR and hemoglobin levels decreased significantly as CRF advanced. Creatinine, urea, triglycerides, phosphate, and CaxP
Discussion
In this study, we have determined the plasma VEGF levels in patients with CRF stage 1 to 5, and we have tried to find the factors affecting its level in this population. This is the first study that shows an association between plasma VEGF levels, markers of renal function, oxidative stress and inflammation in patients with CRF. We also showed, that this effect is linear and is present already in patients with mild renal insufficiency. However, in the multiple regression analysis model the
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