Effects of statins on renal function.
This report reviews data on the development of proteinuria in patients with chronic kidney disease who are treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) for dyslipidemia. Although subgroup analyses of statin trials have shown cardiovascular benefits in subjects with chronic kidney disease, concern about statin-induced proteinuria remains high. Experimental studies have suggested that the proteinuria seen with statin treatment results from the inhibition of receptor-mediated endocytosis, the likely mechanism of protein uptake in proximal tubular cells. Transient proteinuria may signify little more than the effective inhibition of cholesterol synthesis at this site. The blockade of protein trafficking in tubular cells is thought to reduce inflammation, slow fibrosis, and diminish proteinuria in the long term. Post hoc analyses of large clinical trials in subjects without overt renal disease have generally supported this notion, showing that statins most benefit patients with the greatest baseline renal deficits. Statins have also been shown to preserve glomerular filtration rate and reduce proteinuria in subjects with nondiabetic renal disease. In conclusion, in the absence of prospective, randomized trials in renally impaired patients, the collective evidence indicates that statin therapy may slow the decrease in renal function that generally attends atherosclerotic disease. The incidence of proteinuria with potent statins is only 1% to 2% when these drugs are given in recommended doses. Several large trials are currently under way to examine the safety and efficacy of statins in renally compromised patients at high risk for cardiovascular disease.
Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. ragarwal@iupui.edu
Rajiv
R
Agarwal
D000818:Animals; D003928:Diabetic Nephropathies / Q000139:chemically induced; D050171:Dyslipidemias / Q000188:drug therapy; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015994:Incidence; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000139:chemically induced; D016030:Kidney Transplantation; D011507:Proteinuria / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents