The role of lipids in progressive glomerular disease.
The role of lipids in the pathogenesis of focal glomerulosclerosis (FGS) was evaluated using two chemically different lipid lowering agents, clofibric acid and mevinolin. Pharmacologically, these two agents have different mechanisms of action. Clofibric acid affects both cholesterol and triglyceride metabolism, while mevinolin inhibits 3-hydroxy-3 methyl-glutaryl coenzyme A reductase, the rate limiting enzyme in cellular cholesterol synthesis. In two different models of FGS in which hyperlipidemia occurs, the obese Zucker rat and the 5/6 nephrectomy model, both agents significantly reduced FGS and albuminuria. Since glomerular hemodynamic function is normal in obese Zucker rats, these results suggested that lipids are an independent factor in the pathogenesis of FGS. Moreover, in the 5/6 nephrectomy model, the beneficial effects on glomerular structure of reducing serum lipids occurred despite persistent systemic and glomerular hypertension. Thus, we postulated that a synergistic interaction between lipids and hypertension might exist in the pathogenesis of FGS.
Keane
W F
WF
Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis 55415.
Kasiske
B L
BL
O'Donnell
M P
MP
D000818:Animals; D002995:Clofibric Acid / Q000494:pharmacology; D005921:Glomerulonephritis / Q000209:etiology*; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications; D006977:Hypertension, Renal / Q000150:complications / Q000378:metabolism; D050356:Lipid Metabolism; D008148:Lovastatin / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker
D002995:Clofibric Acid; D008148:Lovastatin