URINARY ANGIOTENSINOGEN EXCRETION IN NORMALS AND PATIENTS WITH TYPE II DM

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 糖尿病肾病是糖尿病的严重并发症，其发病机制尚不清楚。来自实验动物模型的证据表明，糖尿病与肾组织肾素-血管紧张素系统的早期激活有关，即使全身性肾素-血管紧张素系统受到抑制。此外，临床研究表明，阻断肾素-血管紧张素系统可以延缓从轻度肾病到终末期肾病的进展，血管紧张素阻滞剂现在是糖尿病伴微量白蛋白尿患者的标准治疗方法。我们首次开发了一种检测人尿中血管紧张素原的方法，这是唯一已知的血管紧张素前体。这项研究测试了尿血管紧张素原的测定是否可以作为局部肾脏肾素-血管紧张素系统活性的标志，以及2型糖尿病患者尿血管紧张素原水平是否、多早和在多大程度上升高。这项研究预期，糖尿病受试者尿液血管紧张素原测定可以预测肾脏损害的程度，并可用于识别阻断肾素-血管紧张素系统有益的受试者。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetic nephropathy is a devastating complication of diabetes mellitus and its pathogenesis remains unclear. Evidence from experimental animal models indicates that diabetes is associated with an early activation of the renal tissue renin-angiotensin system even when the systemic renin-angiotensin system is suppressed. In addition, clinical studies have shown that blockade of the renin-angiotensin system delays progression from mild to end-stage renal disease, and angiotensin blockers now constitute standard therapy in diabetic subjects with microalbuminuria. We have developed an assay for human angiotensinogen, the only known precursor of angiotensin, in human urine for the first time. This study tests whether measurement of urinary angiotensinogen can serve as a marker for the activity of the local kidney renin-angiotensin system and whether, how early and to what extent urinary angiotensinogen levels are elevated in type-2 diabetes mellitus. This study anticipates that urinary angiotensinogen measurement in diabetic human subjects can predict the extent of kidney damage and can be employed to identify subjects in whom blockade of the renin-angiotensin system would be beneficial.