The Research On Association Between Dickkopf-1 And Abdominal Aortic Calcification And Arteriosclerosis In Peritoneal Dialysis Patients

Objective: During the long-term progression of chronic kidney disease(CKD),the body may have different degrees and different parts of metastatic calcification due to mineral and bone metabolism lesions.Among which vascular calcification and arteriosclerosis caused by calcification are one of the common manifestations.It is a good indicator to predict the morbidity and mortality of cardiovasculardisease(CVD)in CKD patients.The latest data showed that vascular calcification occurs at an extremely high rate in patients who require blood purification treatment at the end stage.It has been reported that Wnt/β-catenin signaling pathway was involved in calcification of blood vessels and soft tissues at home and abroad,and was overexpressed in calcification and calcification defense.As an endogenous antagonist of the Wnt signaling pathway,Dickkopf-1(DKK1)couid prevent the formation of active Wnt complexes and affect the calcification of blood vessels and soft tissues.However,the relationship between DKK1 and vascular calcification and arteriosclerosis was not yet clear,especially whether DKK1 could be used as a new biomarker to predict the occurrence of cardiovascular disease in patients with peritoneal dialysis(PD).In this study,clinical data including serum levels of DKK1,AACs and ba PWV were investgated in PD patients with the aim of exploring the relationship between serum DKK1 expression and vascular calcification and arteriosclerosis,and to optimize the prevention of cardiovascular disease.Method:Patients with PD for more than 3 months were randomly selected from the Department of Nephrology,Second Hospital of Hebei Medcial University,and relevant data were collected in the meantime.Serum DKK1 was determined by enzyme-linked immunoassay(ELISA).Lateral abdominal plain film was performed to estimated the calcification of the abdominal aortic,and the degree of abdominal aortic calcification was calculated by AACs.The large artery stiffness was assessed by brachial ankle pulse wave conduction veiocity using arteriosclerosis detection device.Using logistic regression analysis to search the risk factors of abdominal aortic calcification and arteriosclerosis.Structuring the receiver operating characteristic cure(ROC)to evaluated the clinical significance of serum DKK1 level in predicting abdominal aortic calcification and arteriosclerosis in PD patients.Results:1.General information on peritoneal dialysis patients:Among the 77 cases of PD patients,42 were male and 35 were female.The average age was(46.04±12.43)years and the average dialysis age was 25(10～34.5)months.Patients were divided into normal group and abdominal aortic calcification group according to whether the AACs of the lateral abdominal plain film was greater than 0.According to the comparison in pair,we found that the age,SBP,PP,LDL,Hb Alc,AACs,and ba PWV indicators in abdominal aortic calcification group were relatively higher.and the blood Scr and serum DKK1 levels were lower than those in the normal group,the difference was statistically significant(P<0.05).According to the test results of the arteriosclerosis tester,the patients were divided into the normal group and the arteriosclerosis group at 1400cm/s.The comparison between the two groups suggested that the indexes of age,SBP,DBP,PP,FBG,Hb Alc,AACs and ba PWV of patients in the arteriosclerosis group were higher than those of the normal group,and the serum DKK1 level was lower(P<0.05).The history of phosphorus bond and ACEI/ARB medication was statistically different(P<0.05).2.Single factor correlation analysis of serum DKK1:Single-factor linear correlation analysis showed that serum DKK1 was negatively correlated with age,SBP,DBP,PP,FBG,Hb Alc,LDL,hs-CRP,AACs,ba PWV,and had nothing to do with other indicators.3.Correlation analysis of serum DKK1 and abdominal aortic calcification:3.1 Among 77 PD patients,the percentage of abdominal aorta calcification reached 83.1%,and light,moderate,and severe calcification accounted for16.9%,37.7%,and 28.6%,respectively.3.2 Analyzing the occurrence and distribution of abdominal aortic calcification in PD patients with different past medical history,the risk of abdominal aortic calcification in diabetic patients was higher than that in non-diabetic patients.Among them,the risk of mild and moderate calcification was lower than that in non-diabetic patients.The risk of severe calcification was higher than that of non-diabetic patients.Compared with non-hypertensive patients,patients with cardio-cerebrovascular disease and patients without cardio-cerebrovascular disease have no statistically significant differences in the incidence of abdominal aortic calcification and the distribution of calcification.3.3 Linear correlation analysis showed that AACs increased with the increase of age,SBP,PP,FBG,Hb Alc,LDL,ba PWV,and decreased with the increase of serum DKK1.3.4 One-way analysis of variance: The serum DKK1 level of the abdominal aortic calcification group was lower than that of the non-calcification group.By comparing any two groups in the calcification group,we found that only the serum DKK1 level of the moderate and the severe calcification group was lower than that of the mild calcification group(P<0.05).Although the serum DKK1 level of the severe calcification group was lower than that of the moderate calcification group,the difference was not statistically significant(P>0.05).3.5 Logostic regression analysis showed that advanced age,advanced dialysis age,hypertension,diabetes,high phosphorus,high i PTH,low magnesium,and low serum DKK1 were independent risk factors for abdominal aortic calcification.3.6 ROC curve prompts: The area under the curve(AUC)of DKK1 predicting abdominal aortic calcification was 0.875(95%CI 0.771～0.979,P=0.000).When the serum DKK1 level was 9929.82pg/m L as the best cut-off value,the sensitivity and specificity of abdominal aorta calcification were 92.3% and75.0%,respectively.4.Analysis of the relationship between serum DKK1 and arteriosclerosis:4.1 Of 77 patients,52 cases(76.5%)developed arteriosclerosis,55.8% had mild sclerosis,9.1% had moderate sclerosis,and 2.6% had severe sclerosis.4.2 We have analyzed the distribution of arteriosclerosis in PD patients with different past medical history.In patients with hypertension,the incidence of mild,moderate,and severe arteriosclerosis was higher than that of non-hypertensive patients.Compared with non-diabetic patients,diabetic patients have a higher incidence of mild and severe arteriosclerosis,and a lower incidence of moderate arteriosclerosis.4.3 Linear correlation analysis showed that ba PWV increased with the increase of age,SBP,DBP,PP,LDL,hs-CRP,AACs,and decreased with the increase of Alb and serum DKK1.4.4 One-way analysis of variance: The serum DKK1 level of the normal group is higher than that of the arteriosclerosis group with the statistically significant difference(P<0.05).There was no significant difference in serum DKK1 levels between the mild cirrhosis group,the moderate cirrhosis group and the severe cirrhosis group(P>0.05).4.5 Logistic regression analysis showed that old age,high BMI,high SBP,high LDL,high hs-CRP and low serum DKK1 were independent risk factors for arteriosclerosis.4.6 The ROC curve suggested that the AUC of serum DKK1 predicting arteriosclerosis was 0.935(95%CI 0.884～0.987,P=0.000),the corresponding best cut-off point of serum DKK1 level was 9107.47pg/m L,and its sensitivity for predicting arteriosclerosis was 92.0% and the specificity was 76.9%.Conclusions:1.Serum DKK1 level was negatively correlated with the calcification of abdominal aorta score and the conduction velocity of brachial ankle pulse wave.Low level of serum DKK1 was an independent risk factor for calcification and arteriosclerosis of abdominal aorta in CKD patients with PD.2.As a negative regulator,serum DKK1 was involved in the pathological process of vascular calcification in PD patients,whose level could indirectly reflect the vascular calcification.Clinically,the vascular calcification of PD patients can be followed up by measuring serum DKK1 combined with lateral abdominal plain film and brachial and ankle pulse wave transduction velocity examination,so as to detect high-risk patients early and reduce the occurrence of adverse cardiovascular events.However,due to the complexity of the mechanism,there was no recognized best predictive value,so further research was still needed to confirm.