Laboratory Investigation

Kidney International (1988) 33, 667–672; doi:10.1038/ki.1988.51

Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats

Bertram L Kasiske, Michael P O'donnell, Margot P Cleary and William F Keane

Department of Medicine, Division of Nephrology, Hennepin County Medical Center, University of Minnesota, Minneapolis, and University of Minnesota, The Hormel Institute, Austin, Minnesota, USA

Correspondence: Bertram L Kasiske MD, Hennepin County Medical Center, 701 Park Ave, Minneapolis, Minnesota 55415, USA.

Received 16 July 1986; Revised 1 July 1987; Re-revised 5 November 1987.

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Abstract

Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats. Hyperlipidemic obese Zucker rats develop albuminuria and spontaneous focal glomerulosclerosis (FGS) at an early age, despite normal glomerular capillary pressures and nephron plasma flows. To investigate the role of abnormal lipid metabolism in the pathogenesis of FGS, pharmacologic agents were used to reduce serum lipids in male, obese Zucker rats. Eight rats were treated from 8 to 40 weeks of age with the cholesterol synthesis inhibitor, mevinolin (group I). A separate group of seven obese rats was treated with the structurally-unrelated lipid lowering agent, clofibric acid (group II). Results from these two groups were compared to controls injected with vehicle only (group III). Body weight and food intake were similar in all three groups. Mevinolin reduced both serum cholesterol and fasting triglyceride levels while clofibric acid lowered only serum cholesterol. Urine albumin excretion was reduced in groups I and II compared to group III. Mesangial matrix expansion and cellularity were both reduced by mevinolin and clofibric acid. In addition, the percent of glomeruli with focal glomerulosclerosis was much less in groups I (0.4 plusminus 0.1%) and II (1.3 plusminus 0.7%) compared to group III (4.6 plusminus 0.7%, P < 0.05). Micropuncture studies, carried out in separate groups of obese rats, demonstrated that mevinolin and clofibric acid did not affect glomerular hemodynamic function. Although the precise mechanism remains to be defined, these results suggest that abnormal lipid metabolism may be important in the pathogenesis of FGS.

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