Proteolytic enzyme treatment reduces glomerular immune deposits and proteinuria in passive Heymann nephritis

Abstract

We investigated the effect of proteolytic enzyme treatment on the course of passive Heymann nephritis (PHN). PHN was induced by intravenous injection of Heymann antibody into Sprague Dawley rats. Protease-treated rats received intraperitoneal chymopapain and subtilisin. In rats given subnephritogenic doses of Heymann antibody (5 or 10 mg, insufficient to cause proteinuria), glomerular immune deposits were assessed by immunofluorescence and electron microscopy. In rats given 5 mg Heymann antibody and treated with protease in the heterologous phase of the disease (days 1-7), fewer animals were positive for rabbit IgG and rat IgG, as determined by immunofluorescence on day 12, compared with controls (p less than 0.01). Rats given 10 mg Heymann antibody and treated on days 1-5 were less frequently positive for rabbit IgG on day 5 than controls (p less than 0.05). When treatment was given on days 6-12 (autologous phase), fewer rats had glomerular rabbit and rat IgG compared with controls (p less than 0.025). Protease treatment of rats given nephritogenic doses of Heymann antibody (greater than or equal to 40 mg, causing proteinuria) did not result in significant differences in immunofluorescence deposits. However, protease treatment significantly reduced the number of electron dense deposits at all doses of antibody (p less than 0.01). Furthermore, rats given 60 mg Heymann antibody followed by enzyme treatment in the heterologous phase (days 1-7) or throughout the autologous phase (days 6-18) had significantly reduced protein excretion during the autologous phase compared with control rats (p less than 0.05). After onset of significant proteinuria on day 15 in rats given 40 mg Heymann antibody and treated from day 15 until day 25, there was significantly less (p less than 0.05) proteinuria on days 21-22 and 24-25 than in control rats; thus, enzymes could reverse proteinuria. In normal rats, administration of proteases did not have significant effects on urinary protein excretion, serum creatinine, or renal morphology, nor did protease affect anti-rabbit IgG antibody production in rats injected with Heymann antibody. The overall results indicate that proteolytic enzyme treatment can prevent or remove glomerular immune deposits and can prevent or reverse proteinuria.