Hyperlipidemia and kidney disease: Concepts derived from histopathology and cell biology of the glomerulus

Abstract

The association between hyperlipidemia and renal disease was noted by Virchow as earl y as the 19th ce ntury. Subseq ue ntl y, similar histopatho log ica l lipid depo siti o ns we re confirme d in diverse huma n a nd experimental renal diseases. Altho ugh, no studies have been established in man to suggest a causal re lationship between lipid s and the pathogenesis of rena l disease . compe llin g ev id e nce acc umul a te d in experimental animals suggests a direct role of lipids in the initiation and progression of glome rular disease. These studi es showed that cho lesterol-feed ing to various experimental animals induced the development of glomerul ar injury. Furthermore. the treatment of hype rlipidemic a nima ls with lipid lowering drugs prevented the deve lopment of glomenllosclerosis. In this article, we will rev iew recent advances made in understanding various aspects of lipid-mediated rena l injury inc ludin g bioc he mi ca l mec ha nisms of hype rlipidemia, a possible direct role of hyperlipidemi a in the pa th oge nesis o f ren a l disease, pathobiological acc umulation of lipids and lipoprote ins, biochemi cal and histological similarities between systemic atherosclerosis and glomerulosclerosis, and cellular processes invo lved in the development of glomerul ar disease. Furthermore, we will define cellular and mo lecul ar hypotheses that provide putative mechanisms by which hyperlipidemia a nd a theroge ni c lipo pro tei ns indu ce se ri es o f cy toregulatory peptide- med iated eve nts in vo lved in the development of glomerul ar disease.