Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure

B. L. Kasiske, M. P. O'Donnell, W. J. Garvis, W. F. Keane

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309 Scopus citations

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 < 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 < 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 > 0.05) or glomerular capillary pressures (56.6 ± 1.5 mm Hg in treated versus 57.8 ± 0.8 mm Hg in untreated, p > 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. Focal glomerulosclerosis was also reduced by mevinolin (11 ± 2% versus 30 ± 3%, p < 0.01). These results suggest that lipid abnormalities may be important in the pathogenesis of focal glomerulosclerosis in the rat 5/6 nephrectomy model of chronic renal failure.

Original languageEnglish (US)
Pages (from-to)367-374
Number of pages8
JournalCirculation research
Volume62
Issue number2
DOIs
StatePublished - 1988

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