肾素-血管紧张素系统抑制剂(RASI)是IgA肾病(IgAN)患者的首选和基础治疗，然而我们的研究发现约40% 接受标准化RASI治疗的IgAN患者疗效不佳。其发生机制尚不清楚，也缺乏可预测的标志物。我们前期工作发现IgAN患者存在与RASI治疗反应性相关的微小RNA（miRNA）谱。本课题拟在已有研究基础上首先采用高通量RNA测序技术，筛选IgAN患者血清中RASI治疗反应相关的非编码RNA (ncRNA) 表达谱(主要为miRNA及长非编码RNA）；随后利用肾病动物模型及体外足细胞模型探讨在RASI治疗基础上干预目标ncRNA表达对降蛋白尿效应的影响及机制；最后在IgAN患者队列中验证目标ncRNA对RASI疗效的预测价值。本课题将有助于阐明IgAN患者RASI治疗反应差异的发生机制及寻找预测疗效的新型生物标志物，为实现IgAN最优化RASI治疗效应及个体化精准治疗提供新思路。

Renin-angiotensin system inhibitor (RASI) is the first choice and baseline therapy for IgAN patients. However, our ongoing registered clinical trial found that about 40% of IgAN patients showed poor or no response to standard RASI therapy. Currently, the underlying mechanism for resistance to RASI therapy in IgAN remains largely unclear and useful biomarkers for predicting treatment response are also lacking. Our preliminary work showed that there are miRNA profiles related to RASI treatment response in IgAN patients. Based on these, we will firstly collect serum samples before and after RASI therapy from IgAN patients for profiling miRNAs and lncRNAs related to treatment response using RNA sequencing. Secondly, biological functions of candidate ncRNAs will be explored in vivo and in vitro, with an emphasis in additive treatment effect on RASI therapy. Lastly, ncRNA profiles will be tested as biomarkers for predicting treatment response to RASI therapy in IgAN cohort. The study will help to elucidate the mechanisms of different response to RASI therapy and find useful biomarkers to predict treatment response in IgAN, thus may have clinical implications for optimizing efficacy of RASI therapy in IgAN and other chronic kidney diseases.