The Relationship Between Serum8-OHdG And Endothelial Dysfunction And Carotid Intima-media Thickness In Peritoneal Dialysis Patients

Objective: Accelerated atherosclerosis is important cause of increasedmorbidity and mortality in peritoneal dialysis (PD). However, cause of thisincrease cardiovascular morbidity in these patients is not explained bytraditional risk factors alone and various nontraditional factors includingoxidative stress (OS) and endothelial dysfunction have been implicated. OSand endothelial dysfunction are key factors in the development andprogression of atherosclerosis. However, only a few studies have looked atthese factors, their correlates and their relationship with atherosclerosissimultaneously among PD patients of China. This research aimed toinvestigate the affection of oxidative stress in endothelial dysfunction,atherosclerosis in PD patients by8-OHdG, ET-1, eNOS levels and carotidintima-media thickness(CIMT)Methods:80cases of non-diabetic PD patients undergoing regularlyperitoneal dialysis≥3months from the center of the second hospital, hebeimedical univertsity was enrolled.12cases of age and sex-matched healthycontrols. Record the patient’s general situation and clinical indicators aboutdialysis: hemoglobin, albumin, hypersensitive c-reactive protein, totalcholesterol, urea nitrogen, serum creatinine, serum calcium, serum phosphorus,etc. And calculate the urea clearance index (KT/V). Levels of serum8-OHdGwere measured using an enzyme-linked immunosorbent assay (ELISA), levelsof serum ET-1were measured by method of radioimmunoassay, levels ofserum eNOS were measured by method of enzyme nitrate reduction. UsingHD15000(ATL) color doppler ultrasonic diagnostic instrument monitoringcarotid intimal medial thickness. All the data were processed and analysed bySPSS13.0software. Results:1The general data of PD patientsPD group:38cases of men, mean age (41.6±14.03years), mean dialysisduration (median24, range13-44months). The primary disease typesincluded chronic glomerulonephritis (n=60), polycystic kidney (n=3), chronicinterstitial nephritis (n=1), lupus nephritis (n=1), chronic renal failureunknown etiology (n=15).2Carotid color ultrasonic determination resultsCompared with control group, CIMT was higher in PD group, which wassignificantly different (0.92±0.29vs1.21±0.40P<0.01). According to theresults of CIMT, PD patients were divided into two groups. PD patients withatherosclerosis of carotid artery (61cases CIMT≥1.0mm and (or) plaqueformation); PD patients without atherosclerosis of carotid artery (19casesCIMT<1.0mm). The incidence of atherosclerosis in PD patients was76.25%.While in the control group, carotid atherosclerosis (3cases), normal carotidartery (9cases), the incidence of atherosclerosis was25.00%, the incidencebetween the two groups was statistically significant (P<0.01)3The levels of serum8-OHdGCompared with control group, the levels of serum8-OHdG in PDpatients were higher(7.25±0.97ng/ml vs39.33±9.34ng/ml; P<0.01). The levelsof serum8-OHdG were higher in PD patients with atherosclerosis of carotidartery as compared to PD PD patients without atherosclerosis of carotidartery(42.83±7.70ng/ml vs28.07±3.15ng/ml; P<0.01).4The levels of serum ET-1、eNOSCompared with control group, the levels of serum ET-1in PD patientswere higher(16.00±1.41pg/ml vs139.35±31.12pg/ml; P<0.01). The levels ofserum ET-1were higher in PD patients with atherosclerosis of carotid arteryas compared to PD patients without atherosclerosis of carotidartery(147.97±28.49pg/ml vs111.69±22.05pg/ml; P<0.01).Compared with control group, the levels of serum eNOS in PD patientswere decreased(14.25±1.86u/ml vs12.57±1.76u/ml; P<0.01). The levels of serum eNOS were decreased in PD patients with atherosclerosis of carotidartery as compared to PD patients without atherosclerosis of carotidartery(12.14±1.52u/ml vs13.96±1.80u/ml; P<0.01).5The correlation analysis of the levels of serum8-OHdG and someclinical dataThe levels of serum8-OHdG in PD patients were correlated positivelywith age (r=0.697, P=0.000), dialysis duration (r=0.752, P=0.000),hsCRP(r=0.532,P=0.000), systolic blood pressure(r=0.350, P=0.001), diastolicblood pressure(r=0.269, P=0.016), ET-1(r=0.753, P=0.000), CIMT(r=0.863,P=0.000), correlated negatively with KT/V(r=-0.367, P=0.001),eNOS(r=-0.723, P=0.000), and not correlated with ALB, Hb, Scr, BUN,CHOL, Ca, Phos (P>0.05).6The correlation analysis of the levels of serum ET-1and some clinicaldataThe levels of serum ET-1in PD patients were correlated positively withage(r=0.639, P=0.000), dialysis duration (r=0.569, P=0.000), hsCRP (r=0.438,P=0.000), systolic blood pressure (r=0.364, P=0.001), diastolic blood pressure(r=0.280, P=0.002), CIMT(r=0.585, P=0.000),8-OHdG (r=0.753, P=0.000),correlated negatively with KT/V(r=-0.285, P=0.000), eNOS(r=-0.646,P=0.000), and not correlated with ALB, Hb, Scr, BUN, CHOL, Ca Phos (P>0.05).7The correlation analysis of the levels of serum eNOS and some clinicaldataThe levels of serum eNOS in PD patients were correlated negatively withage (r=-0.656, P=0.000), dialysis duration (r=-0.599, P=0.000), systolic bloodpressure (r=-0.299, P=0.007), diastolic blood pressure (r=-0.209, P=0.043),hsCRP (r=-0.408, P=0.000),8-OHdG (r=-0.723, P=0.000), CIMT (r=-0.579,P=0.00), correlated positively with KT/V(r=0.329, P=0.003), and notcorrelated with ALB, Hb, Scr, BUN, CHOL, Ca, Phos(P>0.05).8The correlation analysis of CIMT and some clinical data CIMT in PD patients were correlated positively with age (r=0.549,P=0.000), dialysis duration (r=0.591, P=0.000), hsCRP (r=0.444, P=0.000),systolic blood pressure (r=0.289, P=0.009), diastolic blood pressure (r=0.329,P=0.003), ET-1(r=0.585, P=0.000),8-OHdG (r=0.863, P=0.000, correlatednegatively with KT/V (r=-0.247, P=0.027), eNOS (r=-0.579, P=0.000), andnot correlated with ALB, Hb, Scr, BUN, CHOL, Ca, Phos(P>0.05).9Stepwise multiple regression analysisStepwise multiple regression analysis was used to define independentpredictors of CIMT in PD patients. CIMT was taken as a dependent variable.Age, dialysis duration, hsCRP, systolic and diastolic blood pressure, KT/V,8-OHdG, ET-1, eNOS were incorporated into the model as independentvariables. The regression model reveal that8-OHdG was the only independentpredictors of CIMT(B=0.038, P=0.000) in PD patients.Conclusion:From our results, we can conclude that as compared with controls, PDpatients have higher OS, greater endothelial dysfunction, and increasedstructural atherosclerosis. These abnormalities are closely related with eachother. Oxidative stress was involved in vascular endothelial dysfunction in PDpatients. The levels of surem8-OHdG as an OS marker independently riskfactors for atherosclerosis in PD patients. Antioxidant therapy may reduce theincidence of cardiovascular disease in PD patients.