AMELIORATION OF THE PROGRESSIVE COURSE OF CHRONIC-RENAL-FAILURE IN SUBTOTALLY NEPHRECTOMIZED RATS BY INTRAPERITONEAL ENZYME THERAPY

Aim of the present study was to investigate whether sustained systemic treatment with proteases ameliorates the progressive course of a noni mmune-mediated renal disease. Subtotal nephrectomy in rat was used as a model of chronic renal failure. Phlogenzym (a fu;ed combination of t rypsin, bromelain, and rutin) was used as a model substance. On day 1 after 5/6 nephrectomy, the male Wistar rats were randomized into 2 gro ups: 1 : placebo (P), n = 7, administered daily 2 mi of sterile 0.9% N aCl solution i.p., and 2: verum group (E), n = 7, injected with 12 mg of phlogenzym in the same vehiculum. After 6 weeks the enzyme-treated animals showed lower proteinuria (P: 19.6 +/- 9.1 versus E: 10.2 +/- 6 .2 mg/24 h, p < 0.05). Their plasma creatinine levels were lower (P: 1 06.7 +/- 33.9 vs E: 76.0 +/- 6.3 mu mol/l, p < 0.01), due to higher cr earinine clearance (P: 192.3 +/- 99.4 vs E: 300.5 +/- 47.9 mu l/min/10 0 g, p < 0.05). The groups did not differ by serum urea concentration, although the urea clearance tended to be higher in the enzyme-treated rats. Decreased urinary TGF-beta excretion (P: 0.363 +/- 0.183 vs E: 0.232 +/- 0.085 ng/mg creatinine, p < 0.05) reflected the hindered cyt okine formation in renal tissue. Histomorphologically, cellular infilt ration with mononuclear cells was lower in the E-treated rats, and a d ecline in interstitial fibrosis was observed (expressed as volume frac tion of cortical interstitium; P: 17.2 +/- 1.4, E: 12.3 +/- 0.5%, p < 0.001). Moreover, the activities of lysosomal proteinases (cathepsin B , L+B, and H), which are decreased in the remnant kidney model, were s ignificantly higher in both isolated glomeruli and tubules of the E-tr eated rats. In summary: for the first time evidence for beneficial eff ects of systemic enzyme treatment in a nonimmune-mediated renal diseas e was given. In the rat model of subtotal nephrectomy treatment with e nzymes ameliorated the development of tubulointerstitial fibrosis and the progression of chronic renal failure.