Anderson S, Vora J P
Division of Nephrology and Hypertension, Oregon Health Sciences University, Portland 97201, USA.
J Diabetes Complications. 1995 Oct-Dec;9(4):304-7. doi: 10.1016/1056-8727(95)80028-d.
Glomerular hyperfiltration has long been recognized in insulin-dependent diabetes, and has been more recently recognized in patients with non-insulin dependent diabetes mellitus as well. Experimentally, glomerular hyperfiltration has been shown to result from elevations in the glomerular capillary blood flow and the glomerular capillary hydraulic pressure (PGC). Of the hemodynamic determinants of hyperfiltration, it is glomerular hypertension that is most damaging to the glomerulus. Experimental and clinical studies have confirmed that antihypertensive agents that lower PGC more consistently slow the progression of injury than do those that fail to control glomerular hypertension. The pathogenesis of diabetic hyperfiltration is multifactoral. Many mediators have been proposed, including changes due to the altered metabolic milieu, and alterations in endogenous levels of such vasoactive mediators as atrial natriuretic peptide, endothelial-derived relaxing factor, angiotensin II, prostaglandins, thromboxanes, and kinins, among others. It has more recently been suggested that local renal tissue levels, rather than circulating levels, play the more profound role in hemodynamic regulation. For example, the renin-angiotensin system (RAS) appears to be disproportionately active in the renal tissue, potentially explaining the renal vascular responsiveness to angiotensin-converting enzyme inhibition despite absence of systemic RAS activation. Little is yet known of the mechanisms by which glomerular hypertension leads to injury. Innovative new in vitro systems have been developed to address this question. These studies postulate that glomerular hemodynamic factors (shear stress, pulsatile flow) modify the growth and activity of glomerular component cells, inducing the expression of cytokines and other mediators, which then stimulate matrix production and promote structural injury.
长期以来，人们已经认识到胰岛素依赖型糖尿病患者存在肾小球高滤过现象，最近也发现非胰岛素依赖型糖尿病患者也有这种情况。实验表明，肾小球高滤过是由肾小球毛细血管血流量增加和肾小球毛细血管液压（PGC）升高所致。在高滤过的血流动力学决定因素中，肾小球高血压对肾小球的损害最大。实验和临床研究证实，与未能控制肾小球高血压的药物相比，能更持续降低PGC的抗高血压药物能更有效地减缓损伤的进展。糖尿病高滤过的发病机制是多因素的。人们提出了许多介质，包括代谢环境改变引起的变化，以及心房利钠肽、内皮衍生舒张因子、血管紧张素II、前列腺素、血栓素和激肽等血管活性介质内源性水平的改变等。最近有人提出，局部肾组织水平而非循环水平在血流动力学调节中起更重要的作用。例如，肾素-血管紧张素系统（RAS）在肾组织中似乎过度活跃，这可能解释了尽管没有全身RAS激活，但肾血管对血管紧张素转换酶抑制仍有反应。关于肾小球高血压导致损伤的机制，目前所知甚少。已经开发了创新的新体外系统来解决这个问题。这些研究推测，肾小球血流动力学因素（剪切应力、脉动流）会改变肾小球组成细胞的生长和活性，诱导细胞因子和其他介质的表达，进而刺激基质产生并促进结构损伤。
