HMG CoA reductase inhibitors and renoprotection: the weight of the evidence.
Dyslipidemia and the contributions of oxidized low-density lipoproteins (ox-LDL) are independent cardiovascular risk factors. There is growing evidence that dyslipidemia contributes not only to cardiovascular disease but also to the progressive decline of renal function in diabetic and non-diabetic kidney disease. Ox-LDL, by generating inflammation and oxidative stress, contributes to a pro-atherogenic mileu and leads to endothelial dysfunction, subsequent glomerular filtration barrier damage, and progressive renal injury. Chronic kidney disease (CKD), in turn, induces deleterious effects on lipid metabolism. Therefore, by inhibiting cholesterol synthesis and reducing ox-LDL, HMG CoA reductase inhibitors (statins) are attractive therapeutic options to preserve renal function. Current evidence demonstrates a reduction in cardiovascular risk and improved renal outcomes especially in patients with mild to moderate impairment of renal function. Evidence supports a beneficial role of statins thought to extend beyond their lipid-lowering effect, referred to as pleiotropic actions. These actions include modulatory effects on inflammation, oxidative stress and thrombosis, derived from their ability to prevent the formation of isoprenoid intermediates involved in cellular signaling, posttranslational modification of proteins and cellular function. This translates to potential reductions in the rate of decline in GFR in CKD and adverse effects of type 2 diabetes mellitus in the kidney. This review examines the role of statins for reno-protection as well as cardiovascular benefit in patients with CKD.
Romayne Kurukulasuriya
L
L
University of Missouri-Columbia School of Medicine, Diabetes Center, D109 HSC, One Hospital Dr, Columbia, MO 65212, USA.
Athappan
Ganesh
G
Saab
Georges
G
Whaley Connell
Adam
A
Sowers
James R
JR
D050171:Dyslipidemias / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D019317:Evidence-Based Medicine; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control*; D012307:Risk Factors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors