原发性肾病综合征患儿尿液肾损伤标志物检测的临床意义

Clinical significance of detection of urine renal injury biomarkers in children with primary nephrotic syndrome

目的探讨原发性肾病综合征(PNS)患儿尿液肾损伤标志物检测的临床意义。方法收集2016年1月至12月天津市儿童医院肾脏科初发PNS患儿79例,均予足量激素治疗4周,根据患儿对糖皮质激素的反应分为激素敏感(SSNS)组(63例)与激素耐药(SRNS)组(16例),各组根据诊断标准分为单纯型及肾炎型,检测治疗前后尿微量清蛋白(MAlb)、转铁蛋白(TfR)、视黄醇结合蛋白(RBP)、N-乙酰-β-D氨基葡萄糖苷酶(NAG)、α1-微量球蛋白(α1-MG)及β2-微量球蛋白(β2-MG)水平,并对各组各指标进行比较分析。结果治疗前SSNS组RBP、NAG、α1-MG和β2-MG水平[0.91(1.80) mg/L、28.00(31.5) U/L、8.40(14.2) mg/L、0.45(0.35) mg/L]均低于SRNS组[3.94(4.82) mg/L、37.10(18.20) U/L、11.10(21.42) mg/L、0.66(1.41) mg/L],差异均有统计学意义(均P<0.05)。治疗后SSNS组MAlb、TfR、RBP、NAG、α1-MG、β2-MG水平[14.10(5.60) mg/L、0.40(1.60) mg/L、0.26(0.38) mg/L、7.90(9.10) U/L、2.00(4.40) mg/L、0.27(0.35) mg/L]均低于治疗前[MAlb:1 704.00(1 995.60) mg/L、TfR:142.10(81.90) mg/L]和SRNS组治疗后[557.90(1 857.17) mg/L、117.40(102.10) mg/L、4.19(5.15) mg/L、38.80(32.43) U/L、10.85(16.60) mg/L、0.63(0.91) mg/L],差异均有统计学意义(均P<0.05);SRNS组治疗前后除MAlb[治疗前:2 258.75(2 028.43) mg/L]外,余指标改善不明显。治疗前单纯型PNS患儿中SRNS组RBP[2.91(1.84) mg/L]明显高于SSNS组[0.85(0.98) mg/L],肾炎型PNS患儿中SRNS组RBP、NAG、α1-MG和β2-MG水平[5.03(6.74) mg/L、47.50(18.45) U/L、13.95(21.43) mg/L、1.25(1.44) mg/L]明显高于SSNS组[2.20(2.14) mg/L、34.7(22.05) U/L、9.70(7.35) mg/L、0.55(0.36) mg/L ],差异均有统计学意义(均P<0.05)。通过受试者工作特征曲线分析各指标对激素疗效的预测,RBP、NAG、β2-MG差异均有统计学意义(均P<0.05),曲线下面积(AUC)分别为0.858、0.837、0.679,均<0.9,诊断价值不高。采用Logistic回归分析,认定RBP、NAG为影响因素并建立模型。通过这2项指标联合检测,诊断价值较高(AUC为0.956),诊断灵敏度为93.8%时,特异度为82.5%。结论尿RBP、NAG、α1-MG和β2-MG可早期反映PNS,特别是SRNS患儿的肾小管间质损害。联合检测RBP、NAG对激素疗效的预测具有一定价值。

Objective To investigate the clinical significance of detection of urine renal injury biomarkers in children with primary nephrotic syndrome (PNS). Methods Seventy-nine children with PNS at the Department of Nephrology, Tianjin Children′s Hospital were enrolled from January to December 2016, who were given sufficient glucocorticoid for 4 weeks.According to the response to glucocorticoid, they were divided into steroid-sensitive nephrotic syndrome (SSNS) group (63 cases) and steroid-resistant nephrotic syndrome (SRNS) group (16 cases), then they were divided into simple type and nephritic type according to diagnostic criteria.Urinary levels of microalbuminuria (MAlb), transferrin (TfR), retinal binding protein (RBP), N-acetyl-β-D-glucosaminidase (NAG),α1-microglobulin (α1-MG) and β2-microglobulin (β2-MG) were measured in the children before and after treatment, and the data were analyzed by the statistical method. Results Before treatment, the levels of RBP, NAG,α1-MG and β2-MG in the SSNS group [0.91(1.80) mg/L, 28.00(31.5) U/L, 8.40(14.2) mg/L, 0.45(0.35) mg/L]were lower than those in SRNS group[3.94(4.82) mg/L, 37.10(18.20) U/L, 11.10(21.42) mg/L, 0.66(1.41) mg/L], and the differences were statistically significant (all P<0.05);After treatment, the MAlb, TfR, RBP, NAG,α1-MG,β2-MG in the SSNS group [14.10(5.60) mg/L, 0.40(1.60) mg/L, 0.26(0.38) mg/L, 7.90(9.10) U/L, 2.00(4.40) mg/L, 0.27(0.35) mg/L] were lower than those before treatment[MAlb: 1 704.00(1 995.60) mg/L, TfR: 142.10(81.90) mg/L] and those after treatment in the SRNS group[557.90(1 857.17) mg/L, 117.40(102.10) mg/L, 4.19(5.15) mg/L, 38.80(32.43) U/L, 10.85(16.60) mg/L, 0.63(0.91) mg/L], and the differences were statistically significant (all P<0.05). However, before and after treatment, except for MAlb[before treatment: 2 258.75(2 028.43) mg/L], the indicators in the SRNS group were not significantly improved.Before treatment, the RBP in the SRNS group was significantly higher than that in the SSNS group in children with simple type PNS, and the RBP, NAG,α1-MG and β2-MG in the SRNS group were significantly higher than those in the SSNS group in children with nephritic type PNS (all P<0.05). According to receiver operating characteristic curve, there were obvious differences in the urinary levels of RBP, NAG and β2-MG, and area under curve(AUC) was 0.858, 0.837 and 0.679, respectively, all of which were <0.9, so the value of diagnosis was not high.Logistic regression analysis was used to identify RBP and NAG as influencing factors and to establish a model.Through the combined detection of these two indicators, the diagnostic value was higher (AUC was 0.956), and when the diagnostic sensitivity was 93.8%, the specificity could reach 82.5%. Conclusions Urinary RBP, NAG,α1-MG and β2-MG can early reflect tubular interstitial impairment in children with PNS, especially SRNS.Combined detection of RBP and NAG has certain value in predicting the efficacy of glucocorticoid.