Dande Ranadheer R, Peev Vasil, Altintas Mehmet M, Reiser Jochen
Rush University Medical Center, Chicago, IL, USA.
J Diabetes Res. 2017;2017:3232848. doi: 10.1155/2017/3232848. Epub 2017 May 17.
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. DN typically manifests by glomerular hyperfiltration and microalbuminuria; then, the disease progresses to impaired glomerular filtration rate, which leads to ESRD. Treatment options for DN include the strict control of blood glucose levels and pressure (e.g., intraglomerular hypertension). However, the search for novel therapeutic strategies is ongoing. These include seeking specific molecules that contribute to the development and progression of DN to potentially interfere with these "molecular targets" as well as with the cellular targets within the kidney such as podocytes, which play a major role in the pathogenesis of DN. Recently, podocyte membrane protein urokinase receptor (uPAR) and its circulating form (suPAR) are found to be significantly induced in glomeruli and sera of DN patients, respectively, and elevated suPAR levels predicted diabetic kidney disease years before the occurrence of microalbuminuria. The intent of this review is to summarize the emerging evidence of uPAR and suPAR in the clinical manifestations of DN. The identification of specific pathways that govern DN will help us build a more comprehensive molecular model for the pathogenesis of the disease that can inform new opportunities for treatment.
糖尿病肾病（DN）是全球终末期肾病（ESRD）的主要病因。DN通常表现为肾小球高滤过和微量白蛋白尿；随后，疾病进展为肾小球滤过率受损，进而导致ESRD。DN的治疗选择包括严格控制血糖水平和血压（如肾小球内高血压）。然而，新型治疗策略的探索仍在进行中。这些策略包括寻找有助于DN发生和发展的特定分子，以潜在地干扰这些“分子靶点”以及肾脏内的细胞靶点，如足细胞，其在DN的发病机制中起主要作用。最近，发现足细胞膜蛋白尿激酶受体（uPAR）及其循环形式（suPAR）分别在DN患者的肾小球和血清中显著诱导表达，并且suPAR水平升高在微量白蛋白尿出现前数年就能预测糖尿病肾病。本综述的目的是总结uPAR和suPAR在DN临床表现方面的新证据。确定控制DN的特定途径将有助于我们建立一个更全面的疾病发病分子模型，为新的治疗机会提供依据。
