儿童原发性肾病综合征患者血清miR-150水平变化及其临床意义

Study on the Levels and Clinical Significance of Serum miR-150 in Children with Nephrotic Syndrome

目的分析儿童原发性肾病综合征(nephritic syndrome,NS)患者血清miR-150水平变化,评估其作为NS新型辅助诊断标志物临床价值。方法收集2010年3月~2014年5月在南京军区总医院和江苏省中医院住院并确诊的78例原发性NS患儿及南京市儿童医院79例年龄、性别匹配的健康对照儿童血清样本,记录患者及对照临床资料。实时荧光定量PCR技术(quantitative real-time PCR,qRT-PCR)检测和比较NS患儿及对照儿童血清miR-150水平变化,同时测定其血清总蛋白(TP)、清蛋白(ALB)、球蛋白(GLO)、总胆固醇(TC)、三酰甘油(TG)和肾功能指标[尿素(Urea)、肌酐(Cr)、尿酸(Uric acid)和尿蛋白]水平,统计学分析血清miR-150临床价值及与上述指标相关性。结果 NS患儿血清miR-150的水平为101.4(21.29~336.6)fmol/L,明显高于对照组34.11(5.53~134.2)fmol/L(F=3.658,P<0.001)。ROC曲线分析显示,miR-150作为NS诊断的曲线下面积(ROCAUC)为0.892(95%CI=0.843~0.940)。Spearman相关性分析显示,NS患儿血清miR-150水平与GLO(r=-0.231,P=0.042)和TG(r=-0.233,P=0.040)水平均呈显著负相关。逐步多元线性回归分析显示,在校正其他相关因素的影响下NS患儿血清miR-150水平与ALB水平呈显著独立相关(β=0.241,P=0.034;校正r2=0.046)。多因素逻辑回归分析显示,在校正了年龄、性别等因素后,血清miR-150水平是NS的独立危险因素[OR=16.07(95%CI=5.35~48.28),P<0.001]。结论儿童NS患者血清miR-150水平显著升高,且与肾功能损伤和血脂指标密切相关,有望作为其临床辅助诊断新指标。

Objective To investigate the levels and clinical significance of serum miR-150 in children with primary nephrotic syndrome（NS）.Methods Serum samples were collected from 78 NS children and 79 age-and sex-matched control children in Nanjing General Hospital,Jiangsu Province Hospital of TCM and Nanjing Children Hospital from March 2010 to May 2014.Quantitive Real-time PCR（qRT-PCR）assays were used to determine the concentrations of serum miR-150 in NS and control children.The other lipid and renal function parameters including serum TP,ALB,GLO,TC,TG,Urea,Cr,Uric acid and Uric protein were also assessed.Statistical analyzes were used to evaluate the clinical value of serum miR-150 for NS as well as to assess the clinical association between the levels of serum miR-150 and other clinical parameters.Results The ser-um levels of miR-150 were significantly elevated in NS children[101.4（21.29~336.6）fmol/L（F=3.658,P〈0.001）]as compared with controls[34.11（5.53~134.2）fmol/L].ROC curve analysis showed that the area under the receiver operat-ing characteristic curve（AUCROC）was 0.892（95% CI=0.843~0.940）.Spearman rank correlations analyzes showed that the levels of serum miR-150 were significantly negatively associated with GLO（r=-0.231,P=0.042）and TG（r=-0.233,P=0.040）in NS children.Multiple linear regression analyses showed that serum miR-150 was independently associ-ated with serum ALB levels（β=0.241,P=0.034;adjusted r2=0.046）after adjustment of other related factors.Further-more,multivariate logistic regression analysis showed that serum miR-150 an independent risk factor for NS after adjusting other factors including age and gender[OR=16.07（95% CI=5.35~48.28）,P〈0.001].Conclusion The serum levels of miR-150 were markedly elevated in NS children and closely associated with with impaired kidney function as well as lipid pa-rameters,and may have the potential as a novel auxiliary diagnosis marker for assessing the development of NS.