Role of lipids in the progression of renal disease in chronic renal failure: evidence from animal studies and pathogenesis

Abstract

The purpose of this review has been to summarize the effects of lipids on the progression of renal disease in chronic renal failure. Animal studies show that hypercholesterolemia as induced by a high cholesterol diet can aggravate the progression of renal disease in experimental models of chronic renal failure. Hypolipidemic treatment, when given to animals with chronic nephropathy associated with endogenous hyperlipidemia such as in reduced renal mass, obese Zucker rat, PAN nephrosis and the Dahl salt-sensitive rat, results in a reduction in serum lipids levels concomitant with a decrease in the renal damage. Enrichment of the diet with omega-6 PUFA given to rats with reduced kidney mass leads to a reduction in renal damage, probably due to beneficial changes in renal fatty acid composition, while supplementation of a fish oil diet to rats with immune complex nephritis resulted in a similar beneficial effect, probably due to a suppression in the local immunologic processes. The pathogenesis of this effect is still only partially understood. Lipid deposition and oxidation in the renal mesangium, migration of circulatory monocytes into the renal mesangium and their transformation to foam cell, and alterations in renal PUFA metabolism and composition are the main known alterations that accompany lipid-induced renal damage. These alterations, which are similar to those observed in atherosclerosis, lead to alterations in the normal biologic processes in the renal mesangium and terminate in glomerulosclerosis. Extrapolating the data from experimental studies to human renal diseases, it may be assumed that lipid metabolism has a significant impact on the gravity and progression of renal disease in a selected patient population, namely in patients with chronic renal disease. If so, hypolipidemic treatment or administration of certain types of PUFA can be important in the prevention of progression of the renal disease in these patients. Clinical studies are needed to elucidate this issue.