Recent advances in statins and the kidney

Background Experimental and clinical studies have suggested a correlation b etween the progression of renal disease and dyslipidemia. Indeed, apolipopr otein 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 demonstrat ed a beneficial effect on renal structure and function in a variety of mode ls of renal disease. Investigations into the mechanisms whereby reduction o f lipids by lipid-lowering agents benefits renal disease have suggested tha t the 3-hydroxy-3-methylglutaryl coenzyme reductase inhibitors, the so-call ed statin class of lipid-lowering agents, may have additional effects on th e biology of inflammation that are germane to the progression of renal dise ase. Methods. Both in vivo and in vitro studies that investigated secondary mech anisms of statin effects are reviewed. In addition, new studies that invest igated the effects on novel cellular mechanisms are presented. Results. Lipid-lowering agents appear to have biologically important effect s in modulating a variety of intracellular signaling systems involved in ce ll 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 deve lopment of glomerulosclerosis, but also interstitial fibrosis. These potent ially major effects of lipid-lowering agents appear to be related to the ef fects on intracellular synthesis of nonsterol isoprenoids, which are involv ed in prenylation of critical small molecular weight proteins involved in c ell signal transduction. Conclusions. In addition to the beneficial effects of the reduction in seru m lipids, statins and other lipid-lowering agents may influence important i ntracellular pathways that are involved in the inflammatory and fibrogenic responses, which are common components of many forms of progressive renal i njury.