Lipid abnormalities have been implicated in the pathogenesis of glomerulosclerosis in experimental models of
kidney disease. In previous studies it has been shown that
Adriamycin-induced nephropathy is associated with reduced activities of glomerular
proteinases. This observation led to the hypothesis that reduced proteolytic activities may be responsible for mesangial
protein accumulation, which ultimately leads to global
sclerosis of the glomerular tuft. The aim of the present study was to investigate whether
lovastatin treatment, which prevents progressive glomerulosclerosis in experimental
nephrotic syndrome, would also have an effect on glomerular
proteinase activities.
Adriamycin administration resulted in a persistent
nephrotic syndrome with gross
proteinuria (377 +/- 26 mg/24 h),
hypoalbuminemia (2.1 +/- 0.12 vs. 2.8 +/- 0.02 g/dl),
hypercholesterolemia (575 +/- 74 vs. 68 +/- 1.5 mg/dl) and elevated
triglyceride levels (1,155 +/- 78 vs. 57 +/- 8 mg/dl). Glomerular azocaseinolytic activities both at pH 5.4 (-21%) and 7.4 (-37%) were significantly reduced. In contrast to human subjects, nephrotic rats that were treated with
lovastatin displayed reduced
triglyceride levels (767 +/- 134 mg/dl); their serum
cholesterol, however, remained unchanged. In terms of glomerular
proteolytic enzyme activities, the decline in azocaseinolysis at both pH values was, at least partly, prevented by
lovastatin. On the basis of these data, it appears that the beneficial effect of
lovastatin on the evolution of glomerulosclerosis in the nephrotic rat is associated with the conservation of glomerular proteolytic activities.