LOVASTATIN AMELIORATES THE DEVELOPMENT OF GLOMERULOSCLEROSIS AND UREMIA IN EXPERIMENTAL NEPHROTIC SYNDROME

The nephrotic syndrome was induced in uninephrectomized Sprague-Dawley rats using repeated injections of puromycin and protamine sulfate. Preliminary studies demonstrated that the administration of lovastatin (4 mg/kg body weight [BW] subcutaneously [SC] daily) was effective at lowering plasma cholesterol over a 63-day period, although not to normal values. Subsequently, two groups of rats that had been made nephrotic were studied; one group (n = 8) received lovastatin, the other (n = 9) received the vehicle alone. Blood and urine collections were made at days 0, 23, and 60. Clearance studies and renal histology were obtained at day 60. Lovastatin-treated rats had significantly lower cholesterol at day 23 and 60 than vehicle-treated rats (270.5 ± 39.7 v 501.7 ± 81.9 and 148.2 ± 10.7 v 268.2 ± 40.8 mg/dL, P < 0.05). Both groups of rats developed equivalent degrees of proteinuria and hypoalbuminemia. At day 60, the lovastatin-treated rats had a lower urea: 18.3 ± 4.1 v 55.8 ± 9.6 mmol/L (blood urea nitrogen [BUN] 51.2 ± 11.5 v 156.2 ± 27.0 mg/dL, P < 0.002) and greater inulin clearance (1.83 ± 0.42 v 0.82 ± 0.41 mL/min/kg BW, P < 0.05) than the vehicle-treated rats. Neither group was hypertensive and the blood pressure (BP) was similar in both groups. The percentage of glomeruli showing no changes or minimal histological changes was significantly greater in the lovastatin-treated group (26.5% ± 5.7% v 8.33% ± 3.33%, P < 0.02), and there were more glomeruli with global sclerosis in the vehicle-treated group. Thus, reducing the hypercholesterolemia of chronic aminonucleoside of puromycin (PAN) nephrosis with lovastatin lessens the renal impairment and glomerulosclerosis that occur in this model independent of changes in proteinuria or BP. This suggests hypercholesterolemia plays an important role in the pathophysiology of the progression of renal disease in this model. © 1990, National Kidney Foundation, Inc.. All rights reserved.