Evaluation of Plasma Levels of Neopterin and Advanced Oxidation Protein Products in Patients With End Stage Renal Failure and Those on Maintenance Hemodialysis
Background: Chronic inflammation is a common feature of end stage renal disease (ESRD) and haemodialysis patients (HD). It plays a key role in atherosclerotic plaque development which is enhanced by activated macrophages that synthesize neopterin (NP) Oxidative stress demonstrated by the presence of advanced oxidation protein products (AOPP) and acute phase reaction, marked by C- reactive protein (CRP) are predictive for cardiovascular morbidity and mortality in normal subjects and in chronic renal failure patients.
Aim of the work: The aim of the present study was the evaluation of neopterin (NP) and advanced oxidation protein products (AOPPs) in conservatively treated uremic patients as well as in patients on regular hemodialysis ,to throw light on possible use of these parameters to explain the development of atherosclerosis in such patients.
Subjects and methods: The present work was conducted on sixty subjects, of matched age and socioeconomic state. divided into three groups composed of 20 subjects each as follows ; group I consisted of normal healthy volunteers as controls , group II composed of patients with chronic renal failure on conservative treatment and group III consisted of patients with end stage renal disease on maintenance hemodialysis using polysulphone membrane and on bicarbonate dialysis. All studied subjects were subjected to thorough clinical examination, electrocardiography, B-mode ultrasound for carotid intima media thickness(CIMT) and laboratory investigations including: complete urine analysis, fasting serum glucose ,urea ,uric acid, creatinine , cholesterol (total ,high and low density lipoprotein fractions) , triglycerides and high sensitive Creactive protein(Hs-CRP) levels, alanine aminotransferase activity and evaluation of creatinine clearance if possible .Estimation of plasma levels of neopterin (NP)was done by enzyme-linked immunosorbent assay (ELISA) and advanced oxidation protein products (AOPPs) were measured spectrophotometrically.
Results: Plasma neopterin and AOPPs and serum Hs-CRP levels were significantly higher in all patients groups when compared to control group and a positive significant correlation was found between Hs-CRP and NP in ESRD group. Carotid intima media thickness (CIMT) was significantly increased in ESRD and HD group versus control group. There was a positive significant correlation between CIMT and; age, neopterin levels and the presence of plaques in HD patients.
1. Inflammation is a common feature of ESRD and in HD patients as evidenced by the increased levels of the acute phase reactant Hs-CRP.
2. ESRD and HD patients have an increased prevalence of atherosclerosis as evidenced by increased CIMT.
3. Neopterin is an independent predictor of atherosclerosis as evidenced by the positive significant correlation between CIMT and plasma neopterin in HD patients.
4. Haemodialysis may induce repetitive bouts of oxidative stress evidenced by increased plasma level of AOPPs in HD patients.
5. The inflammatory theory of cardiovascular disease in ESRD is supported in this study by the increase of the inflammatory marker neopterin and by the significant correlation between noepterin and C-reactive protein.
Key Words: End stage renal disease (ESRD), haemodialysis patients (HD),neopterin (NP) , advanced oxidation protein products (AOPP)