Microsoft Word - NEF001BF.rtf

William F. Keane, MD, Department of Medicine, Division of Nephrology, Hennepin County Medical Center, 701 Park Avenue South, Minneapolis, MN 55415 (USA) It is widely recognized that once a critical number of nephrons has been damaged, a progressive loss of renal function occurs even if the original cause of renal injury is no longer present [1]. The final pathological picture, i.e. glomerulosclerosis, is remarkably similar regardless of the etiology, suggesting that different causes can ultimately merge into a common pathway of progressive glomerular damage. Several mechanisms have been proposed for this continuous decline in renal function. Hemodynamic factors, coagulation disorders and metabolic abnormalities may all play important roles in the pathogenesis of glomerulosclerosis [1]. Although the potential involvement of lipids in renal damage was suggested by Virchow [2] more than a century ago, there has not been a renewed interest in this issue until recent years [3]. Investigations during the last decade have provided relevant contributions to our understanding of how lipids can contribute to the process of glomerulosclerosis [4, 5]. Experimental Evidence A number of experimental models support a role for lipids in the progression of renal disease. Animals from different species placed on a high cholesterol diet develop hypercholesterolemia and modest glomerulosclerosis [6]. The extent of glomerular injury, in general, correlates with the circulating cholesterol level [6]. Different animal models of hyperlipidemia secondary to proteinuria or other metabolic abnormalities are also associated with glomerulosclerosis and progressive renal injury [5, 6]. Therapeutic interventions with several unrelated antilipemic agents in experimental models of progressive renal disease have slowed the loss of function and prevented the development of glomerulosclerosis [7]. The magnitude of glomerular injury induced by hypercholesterolemia in otherwise normal kidneys appears relatively modest. However, the presence of preexisting glomerular disease [8,9], reduction of the number of nephrons [10,11], or hypertension [12,13] will increase the extent and severity of glomerulosclerosis. Clinical Evidence Although lipid abnormalities are almost a constant feature of kidney diseases [14], few clinical studies have addressed the role of hyperlipidemia in the pathogenesis of progressive renal insufficiency in humans. However, certain lipid disorders appear clearly associated with the development of spontaneous glomerular injury. Patients with a deficient lecithincholesterol acyltransferase activity develop abnormally large lipid-laden lipoproteins, glomerular lipid deposition and renal failure [15]. Another rare disorder, the so-called