title: Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure.
abstract: The role of lipid abnormalities in the pathogenesis of focal glomerulosclerosis was investigated in the rat remnant kidney model of chronic renal failure. Rats subjected to right nephrectomy and two-thirds segmental infarction of the left kidney (5/6 nephrectomy) were treated for 10 weeks with the lipid-lowering agent clofibric acid. Both serum cholesterol and urine albumin excretion were significantly reduced by clofibric acid. At 10 weeks, the percent of glomeruli with focal glomerulosclerosis was 5 +/- 2% in clofibric acid-treated and 24 +/- 5% in untreated 5/6 nephrectomy rats (p less than 0.01). Inulin clearance was greater in clofibric acid-treated than in untreated 5/6 nephrectomy rats (0.28 +/- 0.02 versus 0.22 +/- 0.02 ml/min 100 g body wt, p less than 0.05). Body weight, kidney weight, and systemic blood pressure were not significantly altered by clofibric acid. Micropuncture studies, performed in separate groups of clofibric acid-treated and untreated 5/6 nephrectomy rats, demonstrated elevated single nephron glomerular filtration rates and glomerular capillary pressures 4 weeks after surgery. However, clofibric acid did not significantly alter single nephron glomerular filtration rates (95 +/- 2.1 nl/min in treated versus 97.0 +/- 6.2 nl/min in untreated, p greater than 0.05) or glomerular capillary pressures (56.6 +/- 1.5 mm Hg in treated versus 57.8 +/- 0.8 mm Hg in untreated, p greater than 0.05) in 5/6 nephrectomy rats. In a separate set of experiments, 5/6 nephrectomy rats were treated with the specific cholesterol synthesis inhibitor, mevinolin. Mevinolin improved serum lipid levels and reduced albuminuria in 5/6 nephrectomy rats without causing significant alterations in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Minnesota College of Medicine, Minneapolis.
authors.forename: B L
authors.initials: BL
authors.lastname: Kasiske
authors.forename: M P
authors.initials: MP
authors.lastname: O'Donnell
authors.forename: W J
authors.initials: WJ
authors.lastname: Garvis
authors.forename: W F
authors.initials: WF
authors.lastname: Keane
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000494:pharmacology*; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000209:etiology*; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology* / Q000517:prevention & control; D006949:Hyperlipidemias / Q000150:complications* / Q000188:drug therapy; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000150:complications*; D007678:Kidney Glomerulus / Q000473:pathology; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D009392:Nephrectomy; D009399:Nephrons / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000097:blood
chemical_list: D014280:Triglycerides; D002995:Clofibric Acid; D002784:Cholesterol; D008148:Lovastatin; D002994:Clofibrate