腹膜透析患者冠状动脉钙化相关血清学标志物的筛选及预测价值研究

Screening and predictive value of serum markers related to coronary artery calcification in peritoneal dialysis patients

目的 观察腹膜透析(peritoneal dialysis,PD)患者冠状动脉钙化(coronary artery calcification,CAC)的临床特征,筛选用于评估CAC的血清学标志物,并探讨其在CAC诊断中的应用价值。方法 选取2022年3月—2023年3月在南京市高淳人民医院肾内科行PD治疗的患者,收集临床资料,完善实验室检查,ELISA法检测血清骨硬化蛋白(sclerostin)、去磷酸化未羧化基质Gla蛋白(dephosphouncarboxylated matrix glaprotein,dp-ucMGP)、可溶性生长刺激表达基因2蛋白(soluble growth stimulation expressed gene2,sST2)水平,螺旋CT检测冠状动脉钙化积分(coronary artery calcium scoring,CACS),根据CACS将患者分为无钙化组(CACS=0)、轻度钙化组(0400)。比较4组患者临床资料及血检指标,筛选出可用于评估CAC的血清学标志物。结果 共纳入103例PD患者,其CAC发生率为67.96%(70/103)。4组间患者的年龄(F=9.644,P<0.001)、透析龄(F=8.141,P=0.043)、心血管病占比(F=8.424,P=0.038)、总Kt/V(F=3.775,P=0.013)、碱性磷酸酶(F=7.909,P=0.048)、sclerostin(F=31.513,P<0.001)、dp-ucMGP(F=24.188,P<0.001)、sST2(F=8.691,P=0.034)、B型钠尿肽前体(F=13.922,P=0.003)水平均有差异。Logistic回归分析显示:高龄(OR=1.192,95%CI:1.070~1.327,P=0.001)、低Kt/V(OR=0.006,95%CI:0.000~0.418,P=0.018)、高sclerostin(OR=1.826,95%CI:1.194~2.792,P=0.006)、高dp-ucMGP(OR=1.990,95%CI:1.235~3.207,P=0.005)是CAC发生的独立危险因素。ROC曲线分析显示血清sclerostin、dp-ucMGP及两者联合预测PD患者CAC的曲线下面积分别为0.817(95%CI:0.715~0.919,P<0.001)、0.797(95%CI:0.705~0.889,P<0.001)、0.855(95%CI:0.776~0.935,P<0.001)。结论血清sclerostin、dpucMGP是预测PD患者发生冠状动脉钙化潜在敏感的血清学标志物,有重要的临床应用价值。

Objective To observe the clinical features of coronary artery calcification(CAC)in peritoneal dialysis(PD)patients,to find out serological markers for evaluating CAC,and to estimate their application values for the diagnosis of CAC.Methods The PD patients treated during March 2022 to March 2023 in the Department of Nephrology,Nanjing Gaochun People's Hospital were recruited for this study.Their clinical data were collected,laboratory examinations were improved,and serum sclerostin,dephospho-uncarboxylated matrix glaprotein(dp-ucMGP)and soluble growth stimulation expressed gene 2(sST2)were dtermined by ELISA.Spiral CT was used to assess the coronary artery calcification score(CACS).According to CACS,patients were then divided into non-calcified group(CACS=0),mild calcified group(0<CACS<100),moderate calcified group(100≤CACS≤400)and severe calcified group(CACS>400).Clinical data and serum indexes were compared among the four groups,and the serological markers were then screened for evaluating CAC.Results The prevalence of CAC was 67.96%(70 cases)in a total of 103 PD patients.There were statistical differences in age(F=9.644,P<0.001),dialysis age(F=8.141,P=0.043),cardiovascular disease rate(F=8.424,P=0.038),total Kt/V(F=3.775,P=0.013),alkaline phosphatase(F=7.909,P=0.048),sclerostin(F=31.513,P<0.001),dp-ucMGP(F=24.188,P<0.001),sST2(F=8.691,P=0.034),and B-type natriuretic peptide precursor(F=13.922,P=0.003)among the four groups.Multivariate logistic regression showed that older age(OR=1.192,95%CI:1.070~1.327,P=0.001),low Kt/V(OR=0.006,95%CI:0.000~0.418,P=0.018),higher sclerotin(OR=1.826,95%CI:1.194~2.792,P=0.006),and higher dp-ucMGP(OR=1.990,95%CI:1.235~3.207,P=0.005)were the independent risk factors for CAC.ROC curve analysis showed that the areas under the curve of serum sclerostin,dp-ucMGP and their combined for predicting CAC in PD patients were 0.817(95%CI:0.715~0.919,P<0.001),0.797(95%CI:0.705~0.889,P<0.001),and 0.855(95%CI:0.776~0.935,P<0.001)respectively.Conclusion Serum sclerostin and dp-ucMGP levels are potentially sensitive serological markers for predicting CAC in PD patients,having important value for clinical application.