| Background and objective:Primary nephrotic syndrome (PNS) is one of the most common glomerulopathy that affect children. Its clinical manifestations are high proteinuria, hypoalbuminemia, hyperlipidemia and edema. High proteinuria, hypoalbuminemia and hyperlipidemia are all the risk factors of atherosclerosis (AS). AS is a general complication of nephrotic syndrome in adult, but PNS children rarely appear with clinical symptoms of AS. So how to early recognize the risk of AS and take positive and effective measures to prevent its development to the clinical AS is our focus, and there is still no study about this at home and abroad.Now the pathogenesis of AS is not very clear, especially the mechanism of nephrotic syndrome complicated with AS need more further research. AS is a chronic inflammatory disease, immune reaction is involved in its pathogenesis. Chemokine is a group of cytokines which has the function of chemotaxis, and it is involved in the process of inflammation and immune response. CXC chemokine ligand 16 (CXCL16), also named SR-PSOX, is a CXC chemokine, an adhesion molecule and a cell surface scavenger receptor. CXCL16 exist both in transmembrane-bound and soluble forms, and the function of it depend upon different forms. Soluble CXCL16 can functions as a chemoattractant for CXCR6+ cells, including CD8+ T cells, CD4+ T cells, NK cells and so on. Transmembrane-bound CXCL16 can act as both a cell surface adhesion molecule and a scavenger receptor. As an adhesion molecule it can promote binding and adhesion of CXCR6-expressing cells to different tissue and cells; as a scavenger receptor CXCL16 can mediate the uptake of phosphati-dylserine and oxidized low-density lipoprotein (oxLDL). In recent years, studies found that CXCL16 participate in the development and incidence of various kidney disease and cardiovascular disease.The aim of this study was to observe the changes of carotid arterial structure and function as well as the change of serum CXCL16 and to investigate the relationship between CXCL16 and AS in PNS children. So we can provide certain theoretical basis of the early prevention and treatment (such as CXCL16 targeted therapy) of AS in PNS children.Subjects:122 children with PNS were enrolled in the study. Of whom 82 children were in active state (active group) and 40 cases in remission state (remission group). According to glucocorticoid treatment response, the active group was divided into steroid sensitive group (n=60), steroid dependent group (n=6) and steroid resistance group (n=16); 40 new onset patients were divided into steroid sensitive group (n=32) and steroid resistance group (n=8).120 healthy children were selected as the control group.Methods:All the subjects were received carotid artery ultrasound examination. Carotid intima-media thickness (cIMT), carotid artery diastolic diameter (dD), carotid artery systolic diameter (sD) were measured. We use formulas to calculate carotid artery movement (△D), carotid stiffness coefficient (β), pressure-strain elastic modulus (Ep), arterial compliance (AC), mean wall cross-sectional area (WCSA), mean lumen cross sectional area of the artery (LCSA), mean cross-sectional distensibility coefficient (DC) and incremental elastic modulus (Einc).Blood samples were collected after a 12h overnight fast in the morning. Serum was collected from the fasting blood samples by centrifugation at 4℃. Serum albumin, total cholesterol, triglyceride were determined using automatic biochemical analyzer by bromocresol green method, enzymatic method and GPO-POD method, respectively. High density lipoprotein and low density lipoprotein were determined by the direct method, apolipoprotein A, apolipoprotein B and lipoprotein a were determined by immune turbidimetry. Serum CXCL16 and ox-LDL were determined by ELISA. The 24-hour urine of children in active group was accurately collected and 24-hour urine protein quantity was determined by phenol red method.Result:1.The level of serum lipid in children of each groupPediatric with PNS in active group had significantly higher TC, TG, LDL, apo-A, apo-B, Lp(a) and ox-LDL than remission group and control group (P<0.01) and furthermore, TC, TG, LDL, apo-B, Lp(a) and ox-LDL of remission group were still higher than control group (P<0.05).2.Carotid artery parameters in subjects of each groupcIMT, Ep, WCSA of active group were significantly higher than that of remission group and control group (P<0.05) and furthermore, there were statistical differences of cIMT and WCSA between remission group and control group (P<0.01); △D, AC in active group were significantly lower than remission group (P<0.05); P of active group were higher than control group (P<0.01). In the active group, cIMT in steroid dependent and steroid resistance patients were significantly higher than that of steroid sensitive children (P<0.01), while there were no statistical difference between steroid dependent and steroid resistance patients (P>0.05). In addition, cIMT in 40 new onset PNS children were also significantly higher than that of controls (.P<0.01).3.Serum CXCL16 levels in each groupSerum CXCL16 level in active group were significantly higher than remission group and control group (P<0.01) and at the same time, serum CXCL16 level of remission group were higher than that of control group (P<0.01). In 40 new onset PNS children, serum CXCL16 level in steroid resistance group were significantly higher than that of steroid sensitive group (P<0.05)4.The correlation among indexesSerum CXCL16 level was positively correlated with TC, TG, LDL, apo-A apo-B, Lp (a), ox-LDL,24-hour urine protein quantity, cIMT in PNS children and negatively correlated with serum ALB(P<0.01, respectively). cIMT was positively correlated with TC, TG, LDL, apo-A, apo-B, Lp(a), ox-LDL and negatively correlated with serum ALB (P<0.01, respectively).5.Multiple stepwise regression analysisIn multiple stepwise regression analysis, cIMT was independently associated with TC, CXCL16 and Lp(a) (R2=0.55, β=0.004, P<0.01; β=0.007, P<0.01; β=0.02, P=0.04)oConclusion:1.TC, TG, LDL, apo-B, Lp (a)Kand ox-LDL in active group and remission group of PNS children were increased obviously, suggesting that lipid metabolic disorders persisted in PNS children.2.The carotid arterial structure and function of PNS children were significantly changed compared with controls, suggesting that there were an increasing risk of AS in PNS children. In the active group, cIMT in steroid dependent and steroid resistance patients were significantly higher than that of steroid sensitive individual, suggesting that the risks of AS were more serious in steroid dependent and steroid resistance patients, In addition, cIMT in 40 new onset PNS children were also significantly higher than that of controls, suggesting that the risk of AS was existed in the early stage of onset.3.cIMT was positively correlated with TC, TG, LDL, apo-A, apo-B, Lp(a), ox-LDL, and multiple stepwise regression analysis showed that IMT was independently associated with TC and Lp(a), suggesting that hyperlipidemia as the independent risk factor may aggravate the risk of AS.4.Children with PNS had higher levels of serum CXCL16 in active group and remission group, and correlation analysis showed that serum CXCL16 was positively correlated with TC, TG, LDL, apo-A, apo-B, Lp (a), ox-LDL and 24-hour urine protein quantity and negatively correlated with serum ALB, suggesting that CXCL16 were involved in the pathogenesis of PNS.5.In 40 new onset PNS children, serum CXCL16 level in steroid resistance group were significantly higher than that of steroid sensitive group, suggesting that CXCL16 may be a biological indicator that can be used to predict the steroid treatment effect in the beginning of the disease.6.Serum CXCL16 was positively correlated with cIMT and multiple stepwise regression analysis showed that CXCL16 was independently associated with cIMT, suggesting that CXCL16 was involved in the pathogenesis of AS in PNS children. |
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