Lipids and the progression of renal disease

• Published in: Journal of the American Society of Nephrology 1990-11, Vol.1 (5 Suppl 2), p.S69-S74
• Main Authors: Keane, W F, O'Donnell, M P, Kasiske, B L, Schmitz, P G
• Format: Article
• Language: English
• Subjects: Animals; Disease Progression; Glomerular Mesangium - pathology; Glomerulosclerosis, Focal Segmental - pathology; Humans; Hypercholesterolemia - pathology; Hypertension - pathology; Kidney - pathology; Kidney Diseases - metabolism; Kidney Diseases - pathology; Lipid Metabolism; Lipids - chemistry; Macrophages - metabolism; Models, Biological
• ISSN: 1046-6673

The mechanisms involved in progressive renal injury have been the subject of intense investigation during the past decade. Hemodynamic and nonhemodynamic factors have been implicated in progressive renal damage, including abnormalities of lipid metabolism. The idea that abnormal lipid metabolism may be important in the development and progression of renal injury has intrigued investigators for over 100 years. Studies in models of progressive renal insufficiency have demonstrated that abnormalities in lipid metabolism may participate in the development of glomerular and tubular alterations leading to nephron destruction. This concept has been supported by the demonstration that pharmacologic intervention with different classes of lipid-lowering agents is associated with a reduction in the extent and severity of glomerular and tubular injury. The mechanism whereby hyperlipidemia contributes to renal injury are at present unknown. Morphologically, marked expansion of the mesangial matrix, prior to the development of glomerulosclerosis, suggests the possibility that altered production of mesangial matrix proteins may contribute to glomerular injury. Increased numbers of glomerular monocyte-derived macrophages and foam cells in hyperlipidemic rats have been described. The role that these cells may play in the development of proteinuria and glomerular damage has not been clarified. Biochemically, increased renal tissue content of cholesterol esters and reduced concentrations of essential fatty acids have been described. Whether these changes in tissue lipids contribute to renal injury is also unknown. In addition, persistent hyperlipidemia, particularly hypercholesterolemia, may also lead to glomerular hypertension, possibly through alterations in eicosanoid metabolism. Finally, preliminary data have suggested that oxidized lipoproteins may contribute to the hemodynamic and structural changes described in lipid-induced renal injury. The roles of altered platelet function and other lipid-derived inflammatory mediators are yet to be explored. In conclusion, experimental studies have indicated that hyperlipidemia is an important modulator of nephron damage and may contribute to the progression of renal disease. Whether alterations in lipid metabolism participate in progressive renal insufficiency in humans remains to be determined.