尿液生物标志物早期预测IgA肾病进展风险的应用研究

IgA肾病是我国最常见的慢性肾小球肾炎类型，是进展性慢性肾脏病和终末期肾脏病(ESRD)的最主要病因。缺乏早期预测IgA肾病进展风险的有效方法是目前制约IgA肾病早期治疗的瓶颈问题。现有IgA肾病进展风险的预测指标（牛津病理积分，蛋白尿和eGFR）存在创伤性，敏感性、特异性不高，预测效率有限等问题。本项目拟根据在前期实验研究中发现的与IgA肾病进展风险相关的新生物标志物，利用前瞻性、多中心、大样本病人随访队列，评估这些新生物标志物对IgA肾病进展风险的预测能力；筛选预测准确性最高的生物标志物；确定生物标志物与临床/病理风险因素联合应用对临床风险再分层的改善作用；最后，通过内部和外部队列验证，建立并验证可供临床使用的IgA肾病进展风险预测模型。为早期识别具有进展为ESRD风险的高危IgA肾病患者群提供高效诊断方法，从而使早期干预进展性IgA肾病成为可能。

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and the leading cause of end-stage renal disease (ESRD) in China. About 10%~60% of patients with IgAN will progressed to ESRD, which is an established major health problem responsible for high morbidity and mortality. Early identifying IgAN patients who are at high risk for developing future ESRD would allow risk stratification and improve efficiency in timely renal protection treatment. Currently, renal pathology, estimated glomerular filtration rate(eGFR), and proteinuria are our best means of identifying IgAN patients at high risk of progression to ESRD, which have shortcomings such as invasive, insensitive and inadequate. There is substantial interest in identifying and validating novel biomarkers in IgAN to better identify patients at high risk of rapid loss of renal function. Through basic science and preliminary clinical study on IgAN, we have identified two candidate biomarkers (urinary angiotensinogen，uAGT and urinary matrix metalloprotease 7, uMMP-7), which might serve as noninvasive markers for predicting IgAN progression. The present study will set up a prospective, multicenter, large sample cohorts to investigate the performance of new biomarkers (uAGT and uMMP-7) in predicting IgAN progression (progressing to ESRD). The primary objective is to evaluate the predictive performance of the novel biomarkers for IgAN progression either individually or in combination; to compare their performance with that of previously reported biomarkers or clinic predictive model; and to determine the effect on early risk reclassification by addition of the new biomarkers to the clinic model currently used in clinical practice.