Arterial hypertension and hyperlipidemia as determinants of glomerulosclerosis

Abstract

Arterial hypertension is a dominant pathogenetic factor for glomerulosclerosis. Nevertheless metabolic factors such as hyper- or dyslipoproteinemia may significantly modify and accelerate the process of glomerular scarring. Hyperlipidemia and lipoprotein abnormalities are often encountered in patients with nephrotic syndrome and chronic renal disease. Although the significance of lipid deposition in renal tissue and the role of lipoproteins in the pathogenesis of renal disease in man has not yet been clearly defined, experimental and clinical data indicate a damaging effect of disturbed lipid metabolism on the kidney. In humans glomerular lipid deposition is observed in several genetic diseases, including lecithin-cholesterol acyltransferase activity deficiency. Studies on animals with reduced renal mass, diabetes mellitus or arterial hypertension have shown that hypercholesterolemia increases the incidence of glomerulosclerosis. Especially the interaction of arterial hypertension and dyslipoproteinemia leads to a rapid and pronounced development of glomerulosclerosis. As most of these studies have been performed in the rat, which has a different lipoprotein profile than man, these results should be carefully interpreted with regard to their relevance for humans. In vitro cell culture studies on human glomerular cells have provided insight into the possible cellular mechanisms of lipid-induced glomerular damage. Apoprotein E containing lipoproteins that are pathologically elevated in many renal diseases are avidly taken up by human glomerular cells. Mesangial cells seem to play a central role in the initiation of glomerulosclerosis by proliferation and production of excess extracellular matrix. Lipoproteins are able to stimulate DNA synthesis in these cells and increase the synthesis of mitogens and matrix proteins. The pathogenetic role of modified, oxidized lipoproteins has not yet been elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)