Effect of lipids on glomerular injury and progression of renal disease.
Experimental studies have suggested that the dyslipidemia that frequently accompanies models of progressive renal injury contributes to glomerular and interstitial injury. This concept is supported by experiments demonstrating that while dietary-induced hypercholesterolemia is associated with modest renal injury, in the presence of hypertension or proteinuria, there is a synergistic effect. In addition, strategies to reduce circulating lipids by the use of different classes of antilipemic agents have also significantly ameliorated glomerular injury. The mechanisms whereby lipids contribute to renal injury are still incompletely understood. However, a direct effect of lipids on the biology of mesangial cells has been demonstrated. In addition, evidence supporting a pathogenetic role for oxidatively-modified low density lipoprotein has been developed. Recent experimental studies have also suggested that antilipemic agents, particularly the 3-hydroxy-3-methylglutaryl coenzyme A inhibitor class, modify the proliferative response to various mitogenic substances. Together these data provide compelling support that lipids participate in the pathogenesis of progressive renal disease.
Keane
W F
WF
Department of Medicine, Hennepin County Medical Center, University of Minnesota Medical School, Minneapolis 55415.
D000818:Animals; D002455:Cell Division; D005920:Glomerular Mesangium / Q000166:cytology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007674:Kidney Diseases / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051381:Rats
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D006903:Hydroxymethylglutaryl CoA Reductases