Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on renal function

Pleiotropic, or non-lipid-dependent, effects mediated by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have important clinical implications for the cardiovascular (CV) system. Atherosclerosis is an inflammatory process accompanied by increases in levels of plasma inflammatory markers and accumulation of immune cells within atherosclerotic plaques. Statins not only decrease serum lipid levels, but also inhibit signaling molecules at several points in inflammatory pathways. The anti-inflammatory effects and improved endothelial function associated with statin therapy are thought to be partly responsible for the reduction in CV morbidity and mortality. In analogy, patients with chronic kidney disease administered statins for CV risk reduction show evidence of improved renal function. However, whether statins confer similar protective benefits on the kidney has not been established. Several lines of evidence suggest that similar etiologic and pathological processes may be involved in CV and chronic kidney diseases. If inflammation and functional changes in the renovascular endothelium contribute to the progression of kidney disease, statins are likely to be effective in the treatment of renal disease. In this review, we critically consider emerging data indicating that statins may modulate renal function by altering the inflammatory response of the kidney and renal vasculature to dyslipidemia. Whether the amelioration of renal function by statins is separable from the lipid-lowering effects of these drugs still remains to be delineated. Other questions that remain to be addressed and issues that should be investigated also are presented. (C) 2004 by the National Kidney Foundation, Inc.