Nephrosclerosis: update on a centenarian

Abstract

Nephrosclerosis is an umbrella term defining changes in all compartments of the kidney, changes caused by hypertension and by ageing. Among other lesions, arteriolosclerosis and arteriolohyalinosis play a major role in inducing glomerular ischaemic shrinking and sclerosis along with glomerulomegaly and focal-segmental glomerulosclerosis (FSGS). These lesions are accompanied by tubulointerstitial inflammation and fibrosis that predict the decline of renal function. Nephrosclerosis is a major cause of renal insufficiency in blacks of African descent with a severe, early form of renovasculopathy and a rapid course to renal failure with predominant lesions of FSGS. It seems that in blacks, separate genetic factors independently lead to vascular lesions and to hypertension with a different time-scale of their onset and of their progression, nephroangiosclerosis preceding the onset of hypertension. Conversely, true and histologically identified nephrosclerosis in white Europeans rarely leads to end-stage renal disease in the absence of malignant hypertension. Various animal models demonstrate that renal vascular lesions may exist in the absence of hypertension. These experiments also point to a major role of angiotensin II and of a number of independent and overlapping cellular and molecular pathways in a cascade of inflammatory events that end in renal fibrosis. Two pathophysiologic mechanisms are at work in inducing glomerular lesions and tubulointerstitial fibrosis: a loss of autoregulation of the renal blood flow caused by an arteriolohyalinosis of the glomerular afferent arteriole and ischaemia that fosters the generation of hypoxia inducible-fibrosing factors. Not all antihypertensive drugs equally protect the kidney from nephrosclerosis. Angiotensin II antagonists exert a favourable effect on hyperfiltration. Conversely, dihydropyridine calcium-channel blockers and vasodilators do not withstand the derangement of renal autoregulation.