Division of Nephrology, Department of Medicine, Vanderbilt Medical Center and VA Medical Center, Nashville, Tennessee 37232-2372, USA.
J Clin Invest. 2012 Jan;122(1):13-6. doi: 10.1172/JCI61858. Epub 2011 Dec 27.
Glomerulosclerosis is a general term for scarring of the kidney glomerulus. It cannot be reversed. As glomerulosclerosis accumulates, the diseased kidney progresses to end-stage renal disease. Treatment with inhibitors of the renin-angiotensin system often decreases the rate of progression of glomerulosclerosis in chronic kidney diseases. Although the mechanisms by which these inhibitors mediate their beneficial effects are incompletely understood, it has been suggested that they act, at least in part, by reducing intraglomerular blood pressure and thereby shear stress-induced loss of podocytes, a key component of the glomerular filtration barrier. In this issue of the JCI, Sachs and colleagues provide experimental confirmation of the critical role of tight adhesion of podocytes to the glomerular basement membrane for maintaining glomerular integrity and provide evidence that inhibition of the renin-angiotensin system reduces glomerulosclerosis in animals with less tightly adherent podocytes, presumably by reducing intraglomerular blood pressure.
肾小球硬化是指肾脏肾小球的瘢痕形成,是一种不可逆转的病变。随着肾小球硬化的积累,病变的肾脏逐渐进展为终末期肾病。肾素-血管紧张素系统抑制剂的治疗通常可降低慢性肾脏病中肾小球硬化的进展速度。尽管这些抑制剂发挥其有益作用的机制尚不完全清楚,但有人提出,它们至少部分通过降低肾小球内血压和剪切力诱导的足细胞丢失来发挥作用,足细胞是肾小球滤过屏障的关键组成部分。在本期《临床研究杂志》中,萨克斯及其同事提供了实验证据,证实了足细胞与肾小球基底膜紧密黏附对于维持肾小球完整性的关键作用,并提供了证据表明,肾素-血管紧张素系统的抑制作用可降低黏附不紧密的足细胞动物的肾小球硬化程度,这可能是通过降低肾小球内血压实现的。