Statins and progressive renal disease.
Thanks to the administration of hypocholesterolemic drugs, important advances have been made in the treatment of patients with progressive renal disease. In vitro and in vivo findings demonstrate that statins, the inhibitors of HMG-CoA reductase, can provide protection against kidney diseases characterized by inflammation and/or enhanced proliferation of epithelial cells occurring in rapidly progressive glomerulonephritis, or by increased proliferation of mesangial cells occurring in IgA nephropathy. Many of the beneficial effects obtained occur independent of reduced cholesterol levels because statins can directly inhibit the proliferation of different cell types (e.g., mesangial, renal tubular, and vascular smooth muscle cells), and can also modulate the inflammatory response, thus inhibiting macrophage recruitment and activation, as well as fibrosis. The mechanisms underlying the action of statins are not yet well understood, although recent data in the literature indicate that they can directly affect the proliferation/apoptosis balance, the down-regulation of inflammatory chemokines, and the cytogenic messages mediated by the GTPases Ras superfamily. Therefore, as well as reducing serum lipids, statins and other lipid-lowering agents may directly influence intracellular signaling pathways involved in the prenylation of low molecular weight proteins that play a crucial role in cell signal transduction and cell activation. Statins appear to have important potential in the treatment of progressive renal disease, although further studies are required to confirm this in humans.
Buemi
Michele
M
Department of Internal Medicine, University of Messina, Messina, Italy. Buemim@Unime.it
Senatore
Massimino
M
Corica
Francesco
F
Aloisi
Carmela
C
Romeo
Adolfo
A
Cavallaro
Emanuela
E
Floccari
Fulvio
F
Tramontana
Domenico
D
Frisina
Nicola
N
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001161:Arteriosclerosis / Q000150:complications / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects; D014511:Uremia / Q000150:complications / Q000188:drug therapy
D000924:Anticholesteremic Agents; D018925:Chemokines