狼疮性肾炎患者血清MCSF和SVEP1水平变化及意义

Changes and significances of serum MCSF and SVEP1 levels in patients with lupus nephritis

目的观察狼疮性肾炎(LN)患者血清MCSF、SVEP1水平变化,探讨二者与LN活动性、肾损伤程度的关系及对LN的诊断价值。方法2021年1月-2023年3月青岛市市立医院诊治系统性红斑狼疮(SLE)患者171例为SLE组,发生LN者126例为LN组,未发生LN者45例为非LN组。同期健康体检者90例为对照组。采用ELISA法检测3组入院时血清MCSF、SVEP1水平。比较LN组与非LN组临床症状、血常规、肾功能、估算肾小球滤过率(eGFR)、补体C3、补体C4、抗核抗体等抗体阳性率、24 h尿蛋白定量及血清MCSF、SVEP1水平。LN患者确诊后评估活动性指数、慢性化指数评分;采用Pearson相关法分析LN患者血清MCSF、SVEP1水平与活动性指数、慢性化指数评分的相关性;采用多因素logistic回归分析SLE患者发生LN的影响因素;绘制ROC曲线,评估血清MCSF、SVEP1水平评估SLE患者发生LN的效能。结果(1)SLE组血清MCSF[(28.78±11.72)ng/L]、SVEP1[(1098.18±404.84)ng/L]水平均高于对照组[(7.06±2.16)、(437.13±154.39)ng/L](t=23.486,P<0.001;t=18.900,P<0.001)。(2)LN组胸腔积液(51.59%)、肉眼血尿(56.35%)、抗dsDNA抗体阳性(51.59%)比率及血肌酐[(103.01±51.89)μmol/L]、血尿素[22.15(12.43,36.88)mmol/L]、血清MCSF[(32.90±10.07)ng/L]、血清SVEP1[(1231.73±363.04)ng/L]、24 h尿蛋白定量[1.20(0.73,1.83)g]水平均高于非LN组[31.11%、24.44%、31.11%、(73.91±33.32)μmol/L、13.33(10.73,15.95)mmol/L、(17.23±7.61)ng/L、(724.25±254.43)ng/L、0.29(0.21,0.41)g](χ^(2)=5.593、13.523、5.593,t=4.288、-4.265、9.512、8.642,U=-8.188;P均<0.05),血白蛋白[(26.11±6.54)g/L]、eGFR[(72.70±30.53)mL/(min·1.73 m^(2))]、补体C3[0.29(0.22,0.39)g/L]水平均低于非LN组[(31.73±7.26)g/L、(99.38±40.53)mL/(min·1.73 m^(2))、0.41(0.27,0.57)g/L](t=-4.811、-4.597,U=-3.844;P均<0.05)。(3)126例LN患者活动性指数评分为13.00(11.00,15.00)分,慢性化指数评分为6.00(4.00,7.00)分。LN患者血清MCSF水平与活动性指数评分、慢性化指数评分均呈正相关(r=0.716,P<0.001;r=0.814,P<0.001),血清SVEP1水平与活动性指数评分、慢性化指数评分均呈正相关(r=0.761,P<0.001;r=0.809,P<0.001)。(4)血白蛋白(OR=0.979,95%CI:0.960~0.998,P=0.030)、eGFR(OR=0.977,95%CI:0.956~0.998,P=0.035)、24 h尿蛋白定量(OR=1.012,95%CI:1.001~1.023,P=0.031)、血清MCSF(OR=1.261,95%CI:1.029~1.546,P=0.025)、血清SVEP1(OR=1.005,95%CI:1.001~1.009,P=0.023)是SLE患者发生LN的影响因素。(5)血清MCSF、SVEP1分别以25.11 ng/L、929.82 ng/L为最佳截断值,诊断SLE患者发生LN的AUC分别为0.888(95%CI:0.831~0.931,P<0.001)、0.875(95%CI:0.816~0.921,P<0.001),灵敏度分别为73.81%、78.57%,特异度分别为86.67%、84.44%;二者联合诊断的AUC为0.945(95%CI:0.899~0.974,P<0.001),灵敏度为83.33%,特异度为88.89%。结论SLE患者血清MCSF、SVEP1水平升高,可反映肾脏损伤程度,二者水平升高是SLE患者发生LN的危险因素,二者联合对LN诊断具有较高价值。

Objective To observe the changes of serum MCSF and SVEP1 in patients with lupus nephritis(LN),and to investigate their relationships with the activity of LN and degree of renal injury as well as their values to the diagnosis of LN.Methods Totally 171 patients with systemic lupus erythematosus(SLE)were diagnosed and treated in Qingdao Municipal Hospital from January 2021 to March 2023(SLE group),and were divided into LN group(n=126)and non-LN group(n=45),and another 90 healthy volunteers received physical examination during the same period(control group).ELISA was used to detect serum MCSF and SVEP1 levels on admission.The clinical symptoms,blood routine,renal function,estimated glomerular filtration rate(eGFR),complement C3,complement C4,antibody positivity of antinuclear antibodies,24-h urine protein,serum MCSF and SVEP1 were compared between LN group and non-LN group.The activity index and chronicity index scores were assessed in LN patients after diagnosis.Spearman's correlation coefficient was used to analyze the correlations of serum MCSF and SVEP1 levels with the activity index and chronicity index scores in LN patients.Multivariate logistic regression was used to analyze the influencing factors of LN in SLE patients.ROC curves were plotted to assess the efficiencies of serum MCSF and SVEP1 on diagnosing LN in SLE patients.Results(1)The serum levels of MCSF and SVEP1 were higher in SLE group[(28.78±11.72),(1098.18±404,84)ng/L]than those in control group[(7.06±2.16),(437.13±154.39)ng/L](t=23.486,P<0.001;t=18.900,P<0.001).(2)The proportions of pleural effusion,gross hematuria and anti-dsDNA antibody-positive,and the levels of blood creatinine,blood urea,serum MCSF,serum SVEP1 and 24-h urine protein were higher in LN group[51.59%,56.35%,51.59%,(103.01±51.89)μmol/L,22.15(12.43,36.88)mmol/L,(32.90±10.07)ng/L,(1231.73±363.04)ng/L,1.20(0.73,1.83)g]than those in non-LN group[31.11%,24.44%,31.11%,(73.91±33.32)μmol/L,13.33(10.73,15.95)mmol/L,(17.23±7.61)ng/L,(724.25±254.43)ng/L,0.29(0.21,0.41)g](χ^(2)=5.593,χ^(2)=13.523,χ^(2)=5.593,t=4.288,t=-4.265,t=9.512,t=8.642,U=-8.188;all P values<0.05),and the albumin,eGFR and complement C3 were lower in LN group[(26.11±6.54)g/L,(72.70±30.53)mL/(min·1.73 m^(2)),0.29(0.22,0.39)g/L]than those in non-LN group[(31.73±7.26)g/L,(99.38±40.53)mL/(min·1.73 m^(2)),0.41(0.27,0.57)g/L](t=-4.811,t=-4.597,U=-3.844;all P values<0.05).(3)The activity index score of 126 patients with LN was 13,00(11.00,15.00),and the chronicity index score was6.00(4.00,7.00).The serum MCSF level in patients with LN was positively correlated with the activity index score and the chronicity index score(r=0.716,P<0.001;r=0,814,P<0.001),and the serum SVEP1 level was positively correlated with the activity index score and the chronicity index score(r=0.761,P<0.001;r=0.809,P<0.001).(4)Albumin(OR=0.979,95%CI:0.960-0.998,P=0.030),eGFR(OR=0.977,95%CI:0.956-0.998,P=0.035),24-h urine protein(OR=1.012,95%CI:1.001-1.023,P=0.031),serum MCSF(OR=1.261,95%CI:1.029-1.546,P=0.025)and serum SVEP1(OR=1.005,5%CI:1.001-1.009,P=0.023)were the influencing factors of LN in SLE patients.(5)When the optimal cut-off values of serum MCSF and SVEP1 were 25.11 ng/L and 929.82 ng/L,the AUCs for diagnosing LN were 0.888(95%CI:0.831-0.931,P<0.001)and 0.875(95%CI:0.816-0.921,P<0.001),the sensitivities were 73.81%and 78.57%,and the specificities were 86.67%and 84.44%,respectively.The AUC of the combination of them two was 0.945(95%CI:0.899-0.974,P<0.001),with a sensitivity of 83.33%and a specificity of 88.89%.Conclusion The serum MCSF and SVEP1 levels are elevated in SLE patients,which can reflect the degree of renal injury and are the risk factors of LN in SLE patients,and the combination of them two is of high value to the diagnosis of LN.