Statins and renal diseases: from primary prevention to renal replacement therapy.
In glomerular diseases with nephrotic syndrome or protracted severe proteinuria, alterations of the lipid metabolism occur and are characterized mainly by increase of LDL cholesterol and frequently also of triglycerides and by qualitative abnormalities of HDL cholesterol and LDL cholesterol. In all renal diseases, when renal insufficiency develops, hyperlipidemia also occurs, with a near-elective increase in VLDL and intermediate-density lipoprotein cholesterol and a decrease of mature HDL cholesterol. There is clear evidence that these abnormalities may induce cardiovascular complications and, probably, also an accelerated progression of the renal damage. The inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, the so-called statins, are effective in controlling hypercholesterolemia, even in the more advanced stages of renal failure and in patients who are on maintenance dialysis. This antilipidemic effect of statins combines with other effects--antioxidant, anti-inflammatory, immunomodulatory, and antithrombotic (called "pleiotropic" effects)--as a result of the inhibition of the mevalonate pathway induced by these agents. Also because of these non-lipid-dependent effects, statins could have an antiatherosclerotic and renoprotective effect, which has been demonstrated clearly in vivo on renal cells and in experimental models of nephropathy but is still less evident in human renal diseases. Ongoing large trials will establish more clearly whether such effects are present in renal patients.
Department of Nephrology and Immunology, San Carlo Hospital, 20153 Milan, Italy. giuseppe.damico@scb.sined.net
Giuseppe
G
D'Amico
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000150:complications* / Q000517:prevention & control*; D007962:Leukocytes / Q000378:metabolism; D050356:Lipid Metabolism; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000628:therapy; D011507:Proteinuria / Q000150:complications / Q000175:diagnosis; D017582:Renal Replacement Therapy; D014280:Triglycerides / Q000097:blood
D000975:Antioxidants; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides