急性肾损伤（AKI）是导致慢性肾脏病（CKD）的重要原因。但是AKI后CKD进展的机制仍不清楚。我们的前期研究发现肾-脑肾素血管紧张素系统（RAS）轴活化通过交感神经传入和传出支形成病理正反馈环，促进盐敏感的肾纤维化。我们的最新实验发现，严重缺血性AKI或肾毒性AKI后，肾脏进行性纤维化，伴随肾内RAS持续活化以及肾、脑交感神经活性持续增加。故本项目假设：AKI后，肾脏和中枢通过交感神经反射弧导致肾脏-脑RAS轴的持续活化，这种病理性正反馈环促进AKI向CKD的转化。本项目拟在不同严重程度和不同原因的AKI动物模型上，进一步研究AKI后，CKD进展与肾/脑RAS、交感神经持续活化的关系；揭示肾-中枢交感反射弧/RAS轴的持续活化和“对话”在AKI-CKD进展中的作用及调节机制。并通过在AKI-CKD进展患者的研究证实这一假说的临床意义。该研究将为防治AKI-CKD进展提供新策略。

Acute kidney injury (AKI) is increasingly recognized as a major risk factor leading to progression to chronic kidney disease (CKD). However, the mechanism underlying AKI to CKD transition remains to be determined. Our recent study shows that the renin-angiotensin system (RAS) in the kidneys and brain interact via alterations in afferent and efferent sympathetic activity to promote salt-induced CKD progression. We recently observed a persistent activation of reno-cerebral sympathetic nervous system (SNS) and intrarenal RAS in animal with CKD progression after ischemic or nephrotoxic AKI. Therefore, we hypothesize that the reno-cerebral RAS axis，linked by a reno-cerebral sympathetic reflex, is activated after AKI. This vicious feedback circle contributes to the development of subsequent CKD. In this study, we will investigate the activity of reno-cerebral SNS and RAS in models with CKD progression after ischemic/nephrotoxic/obstructive AKI. We will investigate the role of reno-cerebral sympathetic reflex/RAS axis in the AKI-CKD transition. And we will also confirm this mechanisms in a cohort of patients with AKI-CKD progression. Our research will identify novel regulatory mechanisms underlying AKI-CKD transition, and thereby provides insights into potential new strategies for prevention and management of progressive CKD after AKI.