Expression And Significance Of Sclerostin And DKK1 In Patients With Chronic Kidney Disease

Objective: The study was to investigate the possible association of circulating concentrations of the secreted Wnt signaling inhibitors DKK1 and Sclerostin expression in CKD,and their relationship with calcium and phosphorus metabolism,FGF-23,renal function and others.Methods: We collected 115 patients who first time came to the de partment of nephrology at the second hospital of Hebei University Scho ol of Medicine,from March 2015 to March 2016,According to the stand ard of NKF-K/DOQI(male 59 cases,female 56 cases).Among them,71 cas es of primary glomerular disease,17 cases of hpertensive renal damage,14 cases of diabetic nephropathy,and 13 cases of the others.In addition,co llected 25 healthy physical examination from health examination center of our hospital as control group(male 14 cases,female 11 cases).After a detailed assessment of heart,liver,lung,kidney,bone and endocrine diseases.And divided into 4 groups according to the criteria of eGFR1)CKD1-2:eGFR≥60(ml/min/1.73m2);2)CKD3: 30≤eGFR<59(ml/min/1.73m2);3)CKD4: 15≤eGFR<29(ml/min/1.73m2);4)CKD5: eGFR<15(ml/min/1.73m2)No n-dialysis patients.Serum levels of Sclerostin,FGF-23,and DKK1 were det ermined using an enzyme-linked immunosorbent assay.The data were ana lyzed by SPSS13.0 software.Results:1 Compared with the control group,Scr increased,eGFR decreased fr om CKD stage1-2,the difference was statistically significant(P<0.05).C ompared with the control group and CKD stage1-2,BUN was higher fro m CKD stage3(P<0.05).Compared with the control group and CKD sta ge1-2Hb decreased from CKD stage3,the difference was statistically sig nificant(P<0.05).The levels of serum calcium in CKD groups decreasedgradually,significantly in CKD5(2.11±0.26)mmol/L,Compared with the control group(2.33±1.20)mmol/L and CKD stage1-2(2.31±0.87)mmo l/L,CKD stage3(2.23±0.13)mmol/L,CKD stage4(2.21±0.15)mmol/L,the difference was statistically significant(P<0.05).The levels of serum phos phorus in CKD groups increased gradually,significantly in CKD stage4(1.41±0.84)mmol/L,Compared with the control group(1.03±1.20)mmol/L,CKD stage1-2(1.11±1.02)mmol/L,CKD stage3(1.17±0.26)mmol/L,the difference was statistically significant(P<0.05),The CKD stage5(1.62±0.23)mmol/L was significantly higher than that in CKD stage4(1.41±0.84)mmol/L,and the difference was statistically significant(P<0.05).The level s of serum iPTH in CKD groups increased gradually,significantly in C KD stage4(94.69±13.22)pg/mL,Compared with the control group(20.53±10.00)pg/mL,CKD stage1-2(22.41±11.73pg/mL),CKD stage3(46.15±19.24)pg/mL,the difference was statistically significant(P<0.05).The CKD sta ge5(155.23±79.43)pg/mL was significantly higher than that in CKD sta ge4(94.69±13.22)pg/mL,and the difference was statistically significant(P<0.05).2 The level of Sclerostin increased significantly from CKD sta ge3(49.50±4.39)pg/mL,Compared with the control group(26.57±8.03)pg/mL and the CKD stage1-2(29.40±7.68)pg/mL,the difference was statisticall y significant(P<0.05).The CKD stage4(58.09±9.17)pg/mL was significa ntly higher than that in the CKD stage3(49.50±4.39)pg/mL,the difference was statistically significant(P<0.05),the CKD stage5(98.44±10.63)pg/mL was higher than that in the CKD stage4(58.09±9.17)pg/mL,the differenc e was statistically significant(P<0.05).The level of DKKI increased fro m CKD stage3(36.87±9.07),Compared with the control group(24.05±7.05)pg/ml and the CKD stage1-2(28.14±9.14)pg/mL,the difference was stati stically significant(P<0.05).The level of FGF-23 increased significantly from CKD stage3(45.54±12.4)pg/mL,Compared with the control group(30.94±10.79)pg/mL and CKD stage1-2(32.75±15.59)pg/mL,the differenc e was statistically significant(P<0.05).The CKD stage4(70.34±8.85)pg/mL was significantly higher than that in the CKD stage3(45.54±12.4)pg/mL,the difference was statistically significant(P<0.05),the CKD stage5(123.43±26.9)pg/mL was higher than that in the CKD stage4(70.34±8.85)p g/mL,the difference was statistically significant(P<0.05).3 Correlation analysis showed that serum Sclerostin level is positive ly correlated with age(r=0.27,P<0.01),serum phosphorus(r=-0.727,P<0.01),FGF-23(r=0.795,P<0.01),calcium phosphorus product(r=0.532,P<0.01),iP TH(r=0.726,P<0.01).and negatively correlated with eGFR(r=-7.99,P<0.01),hemoglobin(r=-0.661,P<0.01),serum calcium(r=-0.400,P<0.01)(P<0.01).No correlation with BMI,ALB(P>0.05).The serum level of DKK1 is positive correlationand FGF-23(r=0.548,P<0.01),age(r=0.199,P<0.05)(P<0.01).Not related with Sclerostin,serum phosphorus,calcium phosphor us product,iPTH,eGFR,hemoglobin,serum calcium,BUN,ALB(P>0.05).4 Multivariate linear regression analysis was performed using Sclero stin as the dependent variable,eGFR,iPTH,FGF-23,serum calcium,serum p hosphorus,calcium and phosphorus product as independent variables,eGF R,iPTH,FGF-23,P into the equation,the test P<0.01.It was demonstrat ed that the above four factors were influenced factors of Sclerostin.The regression equation Y(Sclerostin)=21.81+20.76(P)-0.189(eGFR)+0.60(iPTH)+0.069(FGF-23).Performed using DKK1 as the dependent variable,eGFR,iPTH,FGF-23,serum calcium,serum phosphorus,calcium and phosphorus pr oduct as independent variables,the test P<0.05,There was no statistically significant difference.Conclusions: From the CKD stage4 iPTH,serum phosphorus signific antly increased,from the CKD stage5,serum calcium significantly decre ased,The serum level of Sclerostin and FGF-23 was increased from the beginning of CKD stage3,Sclerostin is correlated with FGF-23,DKK1 is correlated with FGF-23,FGF-23 is currently recognized as early pre dictors of CKD-MBD,it can be speculated that Sclerostin,DKK1 can b e used as early predictors CKD-MBD.