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Effects of Protease Therapy in the Remnant Kidney model of Progressive Renal Failure

K Sebekovaa, L. Paczekb, J. Dämmrichc, H. Lingd, V. Spustovaa, Z. Gaciongb, and A. Heidlandd

a Institute of Preventive and Clinical Medicine, Bratislava, Slowakia;
b The Transplantation Institute Warsaw, Poland;
c Institute of Pathology, and
d Department of Internal Medicine, University of Wuerzburg, Germany

Mineral and Electrolyte Metabol. 1997: 23, pp 291-295 

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Abstract

This study investigated whether protease treatment ameliorates the progressive course of chronic failure in the rat model of subtotal nephrectomy. Fourteen male Wistar rats underwent 5/6 nephrectomy, and were randomized into a control group (C, n = 7) given 2 ml of 0.9% NaCl intraperitoneally (i.p.) daily, and a study group (P, n=7) treated with 12 mg combination of trypsin, bromelain and rutosid in 2 ml saline i.p. daily. After 6 weeks treatment, the enzyme group showed lower proteinuria (C:19.6±9.1 vs 10.2±6.2 mg/24 h, p < 0.05). Endogenous creatinine clearance was higher (C: 192.3 ±99.4, P: 300.5 ±47.9 ml/min per 100 g, p < 0.05), while plasma creatinin was decreased (C: 106.7 ± 33.9, P: 76.0 ± 6.3 mmol/l, p < 0.01). Blood urea nitrogen levels did not change, although urea clearance tended to be higher in the protease-treated rats. Decreased renal formation of cytokines was reflected by a lower urinary excretion ratio of transforming growth factor (TGF)-b/creatinine (C: 0.363 ±0.183, P: 0.232 ±0.085 ng TGF-b/mg creatinine, p < 0.05). Renal morphology revealed less infiltration of mononuclear cells and an amelioration of interstitial fibrosis as expressed by the volume index of the cortical region (C: 17.17 ± 1.43; P: 12.3 ±0.5%, p < 0.001). In addition, the activities of lysosomal proteinases (cathepsin B, L + B, and H), which are decreased in the remnant kidney model of chronic renal failure, were significantly higher in the enzyme-treated group both in isolated glomeruli and proximal tubules. The body and kidney weight tended to be lower, probably due to a catabolic action of the enzymes. In summary, we provide evidence that protease treatment may be beneficial in a nonimmune mediated renal disease. Phlogenzym ameliorated the course of chronic renal failure in the rat model of subtotal nephrectomy and retarded the development of tubulointerstitial fibrosis. Decreased cytokine formation in the remnant kidney is supposed to play a key role.

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