Microsoft Word - NEF150BF

P.J. Westenend, MD, Department of Pathology, University Hospital Nijmegen, PO Box 9101, NL-6500 HB Nijmegen (The Netherlands) Dear Sir, The role of lipids in the pathogenesis and progression of glomerulosclerosis has become a focus ofrecent investigation. Some studies suggest that the development of glomerulosclerosis is analogous to that of atherosclerosis [1]. This hypothesis is in part based upon studies in the spontaneously hyperlipidemic obese Zucker rat [2], in rats with an increased dietary intake of cholesterol [3] and on experimental models such as the aminonucleoside [4] and the remnant kidney model [5] in the rat. Pharmacological intervention in lipid metabolism is capable of preventing the development of glomerulosclerosis [2, 5]. Recently, another spontaneously hyperlipidemic rat strain developing glomerulosclerosis with age was reported [6]. Cholesterolfed hyperlipidemic guinea pigs are also susceptible to the development of glomerulosclerosis [7]. In humans, however, primary hyperlipidemia does not seem to be a risk factor for the development of glomerulosclerosis. The Watanabe heritable hyperlipidemic (WHHL) rabbit is an established model for atherosclerosis. We examined kidneys of WHHL rabbits available from a study analyzing the effect of pravastatin (Bristol Myers Squibb, Princeton, N.J., USA) a ß-hydroxy-ß-methylglutarylcoenzyme A reductase inhibitor, on the development of atherosclerosis in this strain [8, 9]. The experimental group (group P, n = 7) was treated from the age of 3 months with pravastatin for a period of 9 months. Pravastatin was administered orally, in an increasing dosage by means of pravas-tatin-enriched chow. The dose administered was 20 mg/kg/day for the first 5 months and 40 mg/kg/day for the last 4 months of the study. A second group of rabbits, matched for age, sex and body weight, served as controls (group C, n = 10). The animals had free access to tap water and were fed 100 g/day of a commercially pelleted diet containing 15.5% digestible protein (LK-04, Hope Farms, Woerden, The Netherlands). Serum lipids were determined every 4 weeks, and the rabbits were sacrificed at 12 months of age. Coronary arteries and the complete aorta from the arch to the iliac bifurcation were examined for intimal atherosclerotic lesions by a point-counting method. The kidneys were processed for light microscopy and stained with either HE, periodic acid Schiff or meth-enamine silver. Baseline plasma total cholesterol levels were comparable (C: 11.26 ± 1.67, P: 12.73 ± 3.00 mmol/l). Pravastatin treatment caused a reduction in plasma total cholesterol of approximately