Therapeutic implications of lipid-lowering agents in the progression of renal disease.
Progressive deterioration in renal function frequently occurs in the absence of the original cause of injury. During the past decade, intense investigations into the factors responsible for progressive nephron destruction have demonstrated that hemodynamic stresses and metabolic and coagulation abnormalities participate in glomerular injury. Hyperlipidemia is a common abnormality in renal disease and is frequently aggravated by protein-uria. Experimentally, therapy with the lipid-lowering agents clofibric acid or lovastatin reduced circulating lipids, particularly cholesterol, decreased proteinuria, and prevented glomerular damage in normotensive and hypertensive models of progressive renal disease. These beneficial effects occurred independently of changes in systemic blood pressure or glomerular injury, supporting the notion that cholesterol or its accompanying changes, or both, were central in lipid modulation of glomerulosclerosis. Clinically, lipid abnormalities are common in patients with renal disease, and atherosclerotic cardiovascular disease is the most frequent cause of death in these patients. Although the role of lipids in atherosclerotic disease has been well established, whether a similar effect of lipids occurs in the microvasculature of the kidney is unknown. Whether therapeutic approaches directed at reducing hyperlipidemia in patients with renal disease will provide a measure of renal protection, as has been seen in experimental models of renal disease, is also unknown.
Keane
W F
WF
Department of Medicine, Hennepin County Medical Center, University of Minnesota Medical School, Minneapolis 55415.
Kasiske
B L
BL
O'Donnell
M P
MP
Schmitz
P G
PG
D000818:Animals; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000503:physiopathology
D000960:Hypolipidemic Agents