Vascular mechanisms of renal fibrosis. Vasculonephropathies and hypertension

Nephrovasculopathies are an increasing cause of end-stage renal failure. Ne phrosclerosis is a common finding in the hypertensive patient. However, gen etic factors play a prominent role in its incidence. Nephrosclerosis is a c ommon cause of early renal failure in blacks of African ancestry, as oppose d to white Europeans, in whom hypertensive nephrosclerosis rarely and slowl y leans to uremia. That primary hypertension is accompanied by arterionephr osclerosis and arteriolonephrosclerosis, by focal and segmental glomerulosc lerosis leading to glomerular obsolescence and by interstitial fibrosis has been established for nearly a century. However, renal vascular lesions can be observed in animal models as well as in some humans, especially blacks in the absence of or preceding the onset of hypertension. This suggests tha t nephroangiosclerosis might stem from a genetic defect in the renal vascul ar bed, a defect closely associated with the hypertensive trait. Atheroscle rotic renal artery stenosis is a major, potentially remediable cause of chr onic renal failure, especially in whites. Its prevalence in the atheroscler otic population is in the order of 15 percent. This figure has obvious bear ing in terms of health cost. Early diagnosis and treatment by angioplasty o r surgery can preclude development to end-stage renal disease and maintenan ce hemodialysis, as renal atrophy due to chronic ischemia resulting from re nal artery stenosis can be halted or partially reversed by revascularizatio n before extensive fibrosis sets in. Finally renal vascular lesions are com monly observed in the course of various nephropathies, even in the absence of hypertension. The relationship between fibrogenesis and these vascular l esions, which develop along with interstitial fibrosis and entail an unfavo rable prognosis in various glomerulopathies, remains to be elucidated. This is especially the case for focal-segmental glomerulosclerosis, membranous glomerulopathy and IgA glomerulonephritis. The pathophysiology of renal fib rosis induced by ischemia is centered on increased generation of angiotensi n II that is fibrogenic owing to interaction with endothelin 1, PDGF-BB and TGF-beta. These notions open perspectives toward pharmacologic means to re tard or even prevent the development of such various ischemic conditions to end-stage renal failure.