Renal damage and hypercholesterolemia

Abstract

Objectives of this study are to investigate/indicate the potential mechanisms of hypercholesterolemia-induced renal injury. We found out that podocyte activation, such as after renal mass reduction, with hyperlipidemia may contribute to podocyte injury those results in development of segmental sclerosis associated with secondary damage to the tubulointerstitium. Other studies stress the pathogenetic roles of macrophage influx and mesangial cell activation/injury (as evidenced by glomerular hypertrophy and matrix accumulation) in lipid-induced glomerular damage. Another hypothesis for renal effect of hypercholesterolemia suggests that hypercholesterolemia impairs systemic vascular reactivity in response to endothelium-dependent vasodilators, which may be mediated partly through increased formation oflipid peroxides. One of the underlying mechanisms for impaired vascular reactivity is an increased release of oxygen radicals that react with nitric oxide (NO) resulting in decrease of NO’s bioavailability and form of peroxynitrite. The impairment also likely is related to increased oxidizability of LDL. Furthermore, oxidized LDL may affect NO bioavailability by modulating the expression of the enzyme endothelial NO synthase. Finally, hypercholesterolemia is associated with pro-inflammatory changes and impaired regulation of tissue perfusion, which may lead to neovascularisation in the renal cortex, which precedes signs of overt renal morphological damage resulting in renal disease progression. Recent experimental studies on hypercholesterolemia-induced renal damage exhibit that hyperlipidemia contributes to the progression of renal disease Further studies are needed to investigate the pathogenetic mechanisms.