Liu Wenjuan, Stanton Robert C, Zhang Zhaoyun
aDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China bRenal Division, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts, USA cInstitute of Endocrinology and Diabetology, Fudan University, Shanghai, China.
Curr Opin Nephrol Hypertens. 2017 Sep;26(5):351-357. doi: 10.1097/MNH.0000000000000344.
Diabetic kidney disease (DKD) is one of the most common complications in diabetes mellitus and accounts for a large proportion of clinical nephrology practice. Studies have shown that the kallikrein-kinin system (KKS) may be involved in several pathogenic mechanisms that contribute to DKD, including oxidative stress, inflammatory cytokines, and profibrotic autacoids. This review focuses on recent research advance on the potential role of the KKS in the development of DKD and its clinical relevance.
A number of recent studies support the idea that there is a protective role of the KKS in diabetes. For example, agents that activate the KKS have shown strong renal protective effects that might highlight its potential to change the clinical practice. In addition, diabetic mice lacking both bradykinin B2 and B1 receptors have worse kidney lesions as compared with wild-type diabetic mice.
Current basic research has demonstrated that pharmacological activation of the KKS improves renal outcomes in diabetes. These findings suggest that this system may be a therapeutic target in preventing and treating DKD.
糖尿病肾病（DKD）是糖尿病最常见的并发症之一，在临床肾脏病实践中占很大比例。研究表明，激肽释放酶-激肽系统（KKS）可能参与了导致DKD的多种致病机制，包括氧化应激、炎性细胞因子和促纤维化自分泌物质。本综述重点关注KKS在DKD发生发展中的潜在作用及其临床相关性的最新研究进展。
近期多项研究支持KKS在糖尿病中具有保护作用这一观点。例如，激活KKS的药物已显示出强大的肾脏保护作用，这可能凸显了其改变临床实践的潜力。此外，与野生型糖尿病小鼠相比，同时缺乏缓激肽B2和B1受体的糖尿病小鼠肾脏病变更严重。
目前的基础研究表明，KKS的药理激活可改善糖尿病患者的肾脏预后。这些发现提示该系统可能是预防和治疗DKD的一个治疗靶点。
