TY - JOUR
T1 - Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure
AU - Kasiske, B. L.
AU - O'Donnell, M. P.
AU - Garvis, W. J.
AU - Keane, W. F.
PY - 1988
Y1 - 1988
N2 - 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.
AB - 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.
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U2 - 10.1161/01.RES.62.2.367
DO - 10.1161/01.RES.62.2.367
M3 - Article
C2 - 3338121
AN - SCOPUS:0023876499
SN - 0009-7330
VL - 62
SP - 367
EP - 374
JO - Circulation research
JF - Circulation research
IS - 2
ER -