尿生物标志物预测急性肾损伤进展和慢性化研究

进展(严重度分期升级)和慢性化（发生慢性肾脏病）是急性肾损伤（AKI）发生后两个最主要的临床后果，是影响病人死亡和长期预后的最主要因素。如何早期预测AKI进展和慢性化是减少病人死亡或进入终末期肾脏病的关键问题。在临床传统指标基础上验证和寻找新的生物标志物预测AKI进展和慢性化将有助于临床医生及时甄别高危病人，提前采取措施保护肾脏，避免肾损伤的持续和进展，改善临床预后。本项目旨在通过建立三个AKI高危住院病人队列，采用前瞻性、多中心、大样本队列研究方法，评估我们之前基础研究发现的新生物标志物（AGT,MMP-7）对人类AKI后进展和慢性化的预测能力；比较新生物标志物和已报道的生物标志物对AKI进展和慢性化的预测价值。最后，建立基于生物标志物和临床危险因素的AKI进展和慢性化风险预测模型，为生物标志物在临床实践中的应用提供新信息，为防治AKI、改善AKI预后的临床转化研究提供新策略。

Acute kidney injury (AKI) is the leading cause threatening hospitalized patients’ life and associates with worse clinical outcomes. AKI also independently associated with increased risk of developing future chronic kidney disease (CKD) and end stage renal disease (ESRD). Early identification of patients who are at high risk for progressing to further stage and/or developing future CKD is helpful for close monitoring and timely intervention, which in turn will improve patients clinical outcomes and save medical cost. Biomarkers, such as NGAL, KIM-1 and IL-18, were used to predicting AKI progression (to higher severity stage) but only showed moderate performance (AUC 0.7~0.75). Lack of high performance biomarker or biomarkers combination hinders early prediction of AKI progressing to further stage or developing future CKD, thus delays timely management and prevention...Through base science and preliminary clinical study on AKI, we have identified two candidate biomarkers (urinary angiotensinogen，uAGT and urinary matrix metalloprotease 7, uMMP-7) for predicting AKI progression. Our preliminary data showed that uAGT levels significantly elevated in AKI stage 1 (KDIGO 2012) patients who subsequently progressed to stage 2 and/or stage 3 compared with those did not progressed. In AKI patients who developed CKD after 3 months, uMMP-7 remained continuously in higher levels compared with those did not developed CKD...The present study will set up three prospective, multicenter, large sample cohorts to investigate the performance of new biomarkers (uAGT and uMMP-7) in predicting AKI progression (progressing to higher stage or developing future CKD). The participants in three cohorts were patients with acute decompensated heart failure, admitted to mixed ICU or acute tubular necrosis (ATN), who enrolled at the day of first diagnosed AKI stage 1. Patients with advance CKD (eGFR<30ml/min/1.73m2) or receiving maintenance dialysis were excluded. The primary objective is to evaluate the predictive performance of the novel biomarkers for AKI progressing to higher stage and developing future CKD 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 risk reclassification by addition of the new biomarkers to the clinic model currently used in clinical practice.