The Relationship Between SOST And DKK1 Protein Levels And Bone Mineral Density And Vascular Calcification In Maintenance Hemodialysis Patients

Objective: Vascular calcification(VC)is a common complication of chronic kidney disease(CKD)and an important cause of morbidity and mortality in CKD patients.The bone-vessel axis is a new perspective for chronic kidney disease and End Stage Renal Disease(ESRD)in recent years and also explains the potential link between chronic kidney disease,abnormal bone metabolism,and vascular calcification.The classical Wnt signaling pathway is involved in bone formation.In recent years,many studies have found that bone sclerostin(SOST)and Dickkopf related protein 1(DKK1)are inhibitors of Wnt signaling pathway.They may not only participate in bone formation,but also play a role in bone metabolism abnormality and vascular calcification in end-stage renal disease.At present,domestic and foreign studies have shown that SOST and DKK1 proteins are closely related to osteoporosis,cancer,diabetes and other diseases,but there are few studies on the relationship between abnormal bone metabolism and vascular calcification in ESRD patients.The purpose of this study was to investigate the levels of serum SOST,DKK1 and Bone mineral density(BMD)and Abdominal aortic calcification(AAC)in patients with maintenance hemodialysis(MHD).Comprehensive evaluation of the feasibility of SOST and DKK1 as a predictor of bone mass abnormality and vascular calcification in clinical,providing a theoretical basis for early clinical intervention and reducing morbidity and mortality.Method:Fifty patients with maintenance hemodialysis in the hemodialysis clinic of Hebei People's Hospital from October 2017 to October 2018 were selected as the experimental group,including 25 males and 25 females,with an average age of 56.94±12.22 years,median dialysis age 29.50(43)months.At the same time,30 healthy controls with age and gender matched with the dialysis group were selected,with an average age of 51.60±14.47 years including 16 males and 14 females.The clinical data of maintenance hemodialysis patients were collected and recorded in detail,including age,sex,body mass index,history of dialysis,primary disease,past history of cardiovascular disease,history of hypertension and history of diabetes mellitus,etc.After 8 hours of fasting in the healthy control group,venous blood was taken at 8 am on the second day.Patients in the maintenance hemodialysis group were fasted for 8 hours,and 5 ml of venous blood was taken on an empty stomach before the morning hemodialysis.The levels of SOST and DKK1 in fasting serum were measured by Enzyme-Linked Immunosorbent Assay(ELISA)kit provided by Wuhan Seville Biotechnology Co.,Ltd.In addition,total blood protein(TP),albumin(albumin,Alb),serum creatinine(Scr),blood urea nitrogen(BUN),uric acid(UA),blood Calcium(Ca),phosphorus(P),intact parathyroid hormone(iPTH),alkaline phosphatase(ALP),C-reaction protein(CRP)and other biochemical indicators were also detected at the same time.The above biochemical indicators were all completed on the Beckman Coulter automatic biochemical analyzer(AU5800).Bone mineral density(BMD)of maintenance hemodialysis patients was measured by dual-energy X-ray.According to the classification and diagnosis criteria of primary osteoporosis in 2017,the patients were divided into normal bone mass group,osteopenia group and osteoporosis group.Abdominal aorta calcification was detected by lateral abdominal plain film in maintenance hemodialysis group.Abdominal aorta calcification score was calculated by Kauppila semi-quantitative integral method to evaluate the degree of abdominal aorta calcification.The dialysis group was divided into non-calcification group,mild calcification group,moderate calcification group and severe calcification group.The clinical data,serum SOST,DKK1 levels and serum biochemical parameters of maintenance hemodialysis patients with different bone mass and different calcification degree were compared.The correlation between bone mineral density,vascular calcification and serum SOST and DKK1 levels were analyzed.Result:1 Comparison of serum SOST and DKK1 levels between the two groups: Compared with the healthy control group,the serum SOST and DKK1 levels of MHD patients were significantly higher than those of the healthy control group(P<0.05).2 Analysis of correlation between serum SOST and DKK1 level and clinical data in patients with MHD.The results showed that serum SOST was positively correlated with age,dialysis age,CRP,and alkaline phosphatase.There was a positive correlation between serum DKK1 and dialysis age,CRP,and alkaline phosphatase.There is a positive correlation between serum SOST and serum DKK1.3 The relationship between bone mineral density and clinical data in maintenance hemodialysis patients:3.1 According to the change of bone mass,among the 50 hemodialysis patients,there were 38 cases(76%)of abnormal bone mass,including 19 males and 19 females;There were 12 cases(24%)of normal bone mass,including 6 males(12%)and 6 females(12%);There were 17 cases(34%)of osteopenia,including 8 males(16%)and 9 females(18%);There were 21 cases(42%)of osteoporosis,including 11 males(22%)and 10 females(20%).3.2 Comparison of clinical data in different bone mass status of MHD patients:3.2.1 Compared with the normal bone mass group,the age of the osteoporosis group was significantly older in the MHD patients(P<0.05).Compared with the osteopenia group,the age of the osteoporosis group was significantly older in the MHD patients(P<0.05);but there was no significant difference in age between the normal bone mass group and the osteopenia group(P>0.05).3.2.2 Compared with the normal bone mass group,the dialysis age of the osteopenia group and the osteoporosis group was significantly prolonged in the MHD patients(P<0.05);Compared with the osteopenia group,the dialysis age of the osteoporosis group was significantly prolonged in MHD patients.(P<0.05).3.2.3 Compared with the normal bone mass group,the urea nitrogen level of the osteopenia group was slightly lower in the MHD patients(P>0.05),and the urea nitrogen level of the osteoporosis group was significantly lower in the MHD patients(P<0.05);There was no significant difference in urea nitrogen levels between the osteopenia group and the osteoporosis group in the MHD patients(P>0.05).3.2.4 Compared with the normal bone mass group,the serum SOST level of the osteopenia group and osteoporosis group was significantly increased in the MHD patients(P<0.05);Compared with the osteopenia group,the serum SOST level of the osteoporosis group was significantly increased(P<0.05).3.2.5 Compared with the normal bone mass group,the serum DKK1 level of the osteopenia group was slightly increased in the MHD patients(P>0.05).Compared with the normal bone mass group and the osteopenia group,the serum DKK1 level of the osteoporosis group was significantly increased in the MHD patients(P<0.05).3.2.6 There were no significant differences in BMI,serum phosphorus,serum calcium and iPTH between the normal group,the osteopenia group and the osteoporosis group in the MHD patients(P>0.05).4 The relationship between abdominal aortic calcification and clinical data in maintenance hemodialysis patients4.1 According to the evaluation of abdominal aortic calcification score,36(72%)cases had abdominal aortic calcification in 50 hemodialysis patients,including 19(38%)males and 17(34%)females.There were 21 cases(42%)in the mild calcification group,including 9 males(18%)and 12 females(24%);there were 11 patients(22%)in the moderate calcification group,including 7 males(14%)and females 4(8%);and 4 cases(8%)in severe calcification group,including 3 males(6%)and 1 females(2%).4.2 Comparison of clinical data of different degrees of calcification in MHD patients:4.2.1 Compared with non-vascular calcification group,the age of the mild calcification group and moderate calcification group was slightly older in the MHD patients(P>0.05),and the severe calcification group had significantly higher age in the MHD patients(P<0.05).Compared with the moderate calcification group,the age of the severe calcification group were significantly increased in MHD patients(P<0.05).4.2.2 Compared with the non-vascular calcification group,the dialysis age of the mild calcification group,the moderate calcification group and the severe calcification group were higher in the MHD patients(P<0.05);Compared with the mild calcification group,the dialysis age of the moderate calcification group and the severe calcification group were higher in the MHD patients(P<0.05);Compared with the moderate calcification group,the dialysis age of the severe calcification group was higher in MHD patients(P<0.05).4.2.3 Compared with the non-vascular calcification group,the serum SOST level of the mild calcification group was slightly increased in the MHD patients(P>0.05),and the serum SOST level of moderate calcification group and severe calcification group was significantly increased(P<0.05);Compared with the mild calcification group,the serum SOST level of the moderate calcification group and the severe calcification group were significantly increased in the MHD patients(P<0.05);Compared with the moderate calcification group,the serum SOST level of the severe calcification group were significantly increased in MHD patients(P<0.05).4.2.4 Compared with the non-vascular calcification group,the serum DKK1 level of the mild calcification group was slightly increased in the MHD patients(P>0.05),and the serum DKK1 level of the moderate calcification group and the severe calcification group was significantly increased(P<0.05);Compared with the mild calcification group,the serum DKK1 level of the moderate calcification group and the severe calcification group was significantly increased in the MHD patients(P<0.05);but there was no significant difference in the serum DKK1 level between the moderate calcification group and the severe calcification group(P>0.05).4.2.5 There were no significant differences in gender,history of diabete,history of hypertension,history of coronary heart disease,and serum calcium,serum phosphorus,and iPTH between the four groups(P>0.05).4.2.6 Spearman correlation analysis showed that AAC score was positively correlated with dialysis age,coronary heart disease history,serum SOST,serum DKK1(P<0.05),but had no significant correlation with serum calcium,serum phosphorus,iPTH and other indicators(P<0.05).4.2.7 Logistic regression analysis showed that history of hypertension,history of coronary heart disease,dialysis age,serum phosphorus,iPTH,serum SOST were independent risk factors for abdominal aortic calcification in MHD patients.The higher the level of serum SOST,the greater the possibility of abdominal aortic calcification.No similar changes were found in serum DKK1.However,after reducing the inclusion and exclusion criteria of Logistic regression analysis,only the history of coronary heart disease,dialysis age,iPTH,serum phosphorus and abdominal aortic calcification were associated.Conclusion:1.The levels of serum SOST and DKK1 in maintenance hemodialysis patients were significantly higher than those in healthy controls.2.Abnormal bone mass and vascular calcification are common in maintenance hemodialysis patients,and the levels of serum SOST and DKK1 are negatively correlated with bone mineral density and positively correlated with vascular calcification.3.Bone mineral density was negatively correlated with age,dialysis age and alkaline phosphatase level,and positively correlated with serum phosphorus and urea level in maintenance hemodialysis patients.4.Abdominal aortic calcification was positively correlated with dialysis age and history of coronary heart disease in maintenance hemodialysis patients.Age,dialysis age,history of coronary heart disease,history of hypertension,serum phosphorus and iPTH could be independent risk factors for vascular calcification in maintenance hemodialysis patients.