Figure 69

The central role of angiotensin II(AII) in promoting progressive kidney failure. Based on studies in which the renin-angiotensin system has been blocked and renal injury ameliorated, it has been suggested that activation of this system is a crucial factor promoting progressive kidney failure. Increased activity of the renin-angiotensin system also may help explain the association between hypertension and progression of renal disease. AII may promote renal injury by several mechanisms. Activation of the renin-angiotensin system is one mechanism leading to an increase in systemic blood pressure, the result of peripheral vasoconstriction. Glomerular hypertension results not only from the increase in systemic blood pressure but also because of the ability of AII to constrict efferent arterioles, contributing to an increase in glomerular pressure. Glomerular hypertension damages the glomerular capillary wall and promotes injury by multiple mechanisms (see Fig. 6-1). An increase in glomerular pressure tends to increase protein filtration directly. In addition, evidence suggests that AII alters the permeability of the glomerular capillary wall to macromolecules, directly increasing protein filtration. By activating mesangial and epithelial cells, proteinuria itself is a factor promoting progressive kidney failure. Evidence also exists that AII directly stimulates production of various growth factors and cytokines by kidney cells, including fibrogenic cytokines such as transforming growth factor-beta and platelet-derived growth factor. Release of these factors has been linked to the development of glomerular sclerosis and interstitial fibrosis. AII also stimulates proliferation and growth of kidney cells that contribute to progression of renal disease.

12o 1oo 8o 60-4o 2o o

12o 1oo 8o 60-4o 200

Remnant

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Remnant AEI Triple

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