Abstract：
BACKGROUND: Renin-angiotensin system inhibitors (RASi) treatment is the basic therapy for IgA nephropathy (IgAN) patients. However, there is few of biomarker that can predict the efficacy of RASi. This study aimed to find urinary exosomal mRNAs related to the therapeutic effect of RASi in the treatment of proteinuria in IgAN patients.
METHODS: We divided IgAN patients in screening cohort into A1 (proteinuria increase at 3 months), B1 (proteinuria decrease less than 50 % at 3 months), C1 (proteinuria decrease more than 50 % at 3 months) groups according to changes of proteinuria after treatment. The urinary exosomes were collected before biopsy, RNAs were extracted and analyzed with the microarray assay. The candidate genes were screened by differentially expressed genes (DEGs) analysis and then validated by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort. A receiver operating characteristic (ROC) curve was used to evaluate gene performance in predicting therapeutic effect on RASi reducing proteinuria in IgAN patients.
RESULTS: ECE1 and PDE1A mRNAs were significantly different among the three groups, and were gradually decreased among A1, B1 and C1 groups. In the validation cohort, the level of urinary exosomal ECE1 and PDE1A mRNAs were also significantly lower in A2 group compared with C2 group(ECE1, P < 0.001;PDE1A, P < 0.01). Besides, the level of ECE1 mRNA was also lower in B2 group compared with C2 group (P < 0.01). The ROC curve verified that urinary exosomal ECE1 and PDE1A gene level predicted RASi efficacy in IgAN patients with area under curve (AUC) 0.68 and 0.63 respectively.
CONCLUSIONS: Urinary exosomal ECE1 and PDE1A mRNAs expression can serve as potential biomarkers for predicting the RASi efficacy to reduce proteinuria in IgAN patients.
METHODS: We divided IgAN patients in screening cohort into A1 (proteinuria increase at 3 months), B1 (proteinuria decrease less than 50 % at 3 months), C1 (proteinuria decrease more than 50 % at 3 months) groups according to changes of proteinuria after treatment. The urinary exosomes were collected before biopsy, RNAs were extracted and analyzed with the microarray assay. The candidate genes were screened by differentially expressed genes (DEGs) analysis and then validated by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort. A receiver operating characteristic (ROC) curve was used to evaluate gene performance in predicting therapeutic effect on RASi reducing proteinuria in IgAN patients.
RESULTS: ECE1 and PDE1A mRNAs were significantly different among the three groups, and were gradually decreased among A1, B1 and C1 groups. In the validation cohort, the level of urinary exosomal ECE1 and PDE1A mRNAs were also significantly lower in A2 group compared with C2 group(ECE1, P < 0.001;PDE1A, P < 0.01). Besides, the level of ECE1 mRNA was also lower in B2 group compared with C2 group (P < 0.01). The ROC curve verified that urinary exosomal ECE1 and PDE1A gene level predicted RASi efficacy in IgAN patients with area under curve (AUC) 0.68 and 0.63 respectively.
CONCLUSIONS: Urinary exosomal ECE1 and PDE1A mRNAs expression can serve as potential biomarkers for predicting the RASi efficacy to reduce proteinuria in IgAN patients.
摘要：
背景：肾素-血管紧张素系统抑制剂（RASi）治疗是IgA肾病（IgAN）患者的基础治疗。然而,很少有生物标志物可以预测RASi的疗效。本研究旨在寻找与RASi治疗IgAN患者蛋白尿疗效相关的尿外泌体mRNA。
方法：我们将筛查队列中的IgAN患者分为A1（3个月时蛋白尿增加），B1（3个月时蛋白尿减少小于50%），C1(3个月时蛋白尿下降50%以上)组治疗后根据蛋白尿的变化。活检前收集尿液外泌体，提取RNA并用微阵列测定进行分析。通过差异表达基因(DEGs)分析筛选候选基因,然后在验证队列中通过定量实时聚合酶链反应(qPCR)进行验证。使用受试者工作特征（ROC）曲线评估基因性能，以预测RASi减少IgAN患者蛋白尿的治疗效果。
结果：ECE1和PDE1AmRNA在三组间有显著差异，A1、B1、C1组逐渐降低。在验证队列中，与C2组相比，A2组的尿外泌体ECE1和PDE1AmRNA水平也显着降低（ECE1，P<0.001；PDE1A，P<0.01)。此外,B2组ECE1mRNA水平也低于C2组（P<0.01）。ROC曲线验证了尿外泌体ECE1和PDE1A基因水平预测IgAN患者的RASi疗效，曲线下面积（AUC）分别为0.68和0.63。
结论：尿外泌体ECE1和PDE1AmRNA的表达可作为潜在的生物标志物，用于预测RASi疗效以减少IgAN患者的蛋白尿。
方法：我们将筛查队列中的IgAN患者分为A1（3个月时蛋白尿增加），B1（3个月时蛋白尿减少小于50%），C1(3个月时蛋白尿下降50%以上)组治疗后根据蛋白尿的变化。活检前收集尿液外泌体，提取RNA并用微阵列测定进行分析。通过差异表达基因(DEGs)分析筛选候选基因,然后在验证队列中通过定量实时聚合酶链反应(qPCR)进行验证。使用受试者工作特征（ROC）曲线评估基因性能，以预测RASi减少IgAN患者蛋白尿的治疗效果。
结果：ECE1和PDE1AmRNA在三组间有显著差异，A1、B1、C1组逐渐降低。在验证队列中，与C2组相比，A2组的尿外泌体ECE1和PDE1AmRNA水平也显着降低（ECE1，P<0.001；PDE1A，P<0.01)。此外,B2组ECE1mRNA水平也低于C2组（P<0.01）。ROC曲线验证了尿外泌体ECE1和PDE1A基因水平预测IgAN患者的RASi疗效，曲线下面积（AUC）分别为0.68和0.63。
结论：尿外泌体ECE1和PDE1AmRNA的表达可作为潜在的生物标志物，用于预测RASi疗效以减少IgAN患者的蛋白尿。
