[The effect of lovastatin on the development of adriamycin nephropathy in rats].

Backgrounds: Hyperlipidemia is not only a prominent complication of nephrotic syndrome, but it may also contribute to the further non-immunologic damage of glomeruli. Analogy between atherosclerosis and glomerular sclerosis was suggested. Treatment of hyperlipidemia may decrease proteinuria in nephrotic animals and subjects and possibly prevent the progression of glomerulosclerosis and renal failure. We decided to study the influence of therapy with the inhibitor of cholesterol synthesis, lovastatin, on the development of the experimental nephrotic syndrome induced by the administration of adriamycine in rats.

Methods And Results: Nephrotic syndrome was induced in rats by the intravenous administration of adriamycine. One group of animals was treated from the time of adriamycine adminstration with lovastatin. Lovastatin was also given to one group of control animals. Proteinuria increased significantly during 4 weeks in untreated adriamycine rats (from 0.93 + 0.57 to 12.76 + 11.95 g/mmol of urinary creatinine, p < 0.01), but it did not change significantly in adriamycine rats treated with lovastatin (from 0.98 + 0.69 to 1.90 + 4.25 g/mmol of creatinine, p = n.s.) and it was significantly lower than in untreated animals (p < 0.01). Plasma albumin decreased 12 weeks after adriamycine administration in untreated rats (from 21.16 + 1.45 to 10.58 + 3.83 g/l, p < 0.001) significantly more (p < 0.05) than in rats treated with lovastatin (from 20.01 + 2.18 to 15.34 + 2.66 g/l, p < 0.01). Lovastatin also ameliorated the increase of plasma cholesterol and eliminated the increase of plasma triglycerides in adriamycine rats. Metabolic changes were in all groups characterized by the increase of free fatty acids, possibly due to exaggerated lipolysis, but without significant change of glycaemia and plasma urea. Proteinuria was decreasing at the end of the observed period. Histologically there were only minimal changes in glomeruli, without significant glomerulosclerosis.

Conclusions: Administration of lovastatin prevented the development of nephrotic syndrome in experimental adriamycine nephropathy in rats. This finding suggests the possible role of hyperlipidemia in the pathogenesis of glomerular damage and suggests the posibility to prevent glomerulosclerosis and renalisufficiency in some form on nephrotic syndrome by the effective hypolipidemic therapy.