H Oda1, W F Keane. 1. Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA.
Abstract
BACKGROUND: Experimental and clinical studies have suggested a correlation between the progression of renal disease and dyslipidemia. Indeed, apolipoprotein B-containing lipoproteins have been demonstrated to be an independent risk factor for the progression of renal disease in humans. Interventional strategies in experimental models of renal disease have clearly demonstrated a beneficial effect on renal structure and function in a variety of models of renal disease. Investigations into the mechanisms whereby reduction of lipids by lipid-lowering agents benefits renal disease have suggested that the 3-hydroxy-3-methylglutaryl coenzyme reductase inhibitors, the so-called statin class of lipid-lowering agents, may have additional effects on the biology of inflammation that are germane to the progression of renal disease. METHODS: Both in vivo and in vitro studies that investigated secondary mechanisms of statin effects are reviewed. In addition, new studies that investigated the effects on novel cellular mechanisms are presented. RESULTS: Lipid-lowering agents appear to have biologically important effects in modulating a variety of intracellular signaling systems involved in cell proliferation, inflammatory responses that involve macrophage adhesion, recruitment, and maturation. In addition, the effects on fibrogenesis have been recently defined. These latter effects may influence not only the development of glomerulosclerosis, but also interstitial fibrosis. These potentially major effects of lipid-lowering agents appear to be related to the effects on intracellular synthesis of nonsterol isoprenoids, which are involved in prenylation of critical small molecular weight proteins involved in cell signal transduction. CONCLUSIONS: In addition to the beneficial effects of the reduction in serum lipids, statins and other lipid-lowering agents may influence important intracellular pathways that are involved in the inflammatory and fibrogenic responses, which are common components of many forms of progressive renal injury.
BACKGROUND: Experimental and clinical studies have suggested a correlation between the progression of renal disease and dyslipidemia. Indeed, apolipoprotein B-containing lipoproteins have been demonstrated to be an independent risk factor for the progression of renal disease in humans. Interventional strategies in experimental models of renal disease have clearly demonstrated a beneficial effect on renal structure and function in a variety of models of renal disease. Investigations into the mechanisms whereby reduction of lipids by lipid-lowering agents benefits renal disease have suggested that the 3-hydroxy-3-methylglutaryl coenzyme reductase inhibitors, the so-called statin class of lipid-lowering agents, may have additional effects on the biology of inflammation that are germane to the progression of renal disease. METHODS: Both in vivo and in vitro studies that investigated secondary mechanisms of statin effects are reviewed. In addition, new studies that investigated the effects on novel cellular mechanisms are presented. RESULTS:Lipid-lowering agents appear to have biologically important effects in modulating a variety of intracellular signaling systems involved in cell proliferation, inflammatory responses that involve macrophage adhesion, recruitment, and maturation. In addition, the effects on fibrogenesis have been recently defined. These latter effects may influence not only the development of glomerulosclerosis, but also interstitial fibrosis. These potentially major effects of lipid-lowering agents appear to be related to the effects on intracellular synthesis of nonsterol isoprenoids, which are involved in prenylation of critical small molecular weight proteins involved in cell signal transduction. CONCLUSIONS: In addition to the beneficial effects of the reduction in serum lipids, statins and other lipid-lowering agents may influence important intracellular pathways that are involved in the inflammatory and fibrogenic responses, which are common components of many forms of progressive renal injury.
Authors: Fionnuala C Cormack-Aboud; Paul T Brinkkoetter; Jeffrey W Pippin; Stuart J Shankland; Raghu V Durvasula Journal: Nephrol Dial Transplant Date: 2008-09-27 Impact factor: 5.992