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Amelioration of the development of chronic renal failure by systemic enzyme treatment in the rat model of 5/6 nephrectomy

Sebeková K.1, Paczek L.2, Dämmrich J.3, Ling H.3, Schenk O.3, Gaciong Z.2, Spustová V.1, Heidland A.3

1 Institute of Preventive and Clinical Medicine, Bratislava, Slovakia
2 Transplantation Institute, Warsaw, Poland
3 University of Wuerzburg, Germany

7th Interscience World Conference on Inflammation, Antirheumatics, Analgesics, Immunomodulators, 1997, May 19-21, Geneva, Switzerland - 
published in Inter. Journal of Tissue Reactions 1997, Vol. XIX, No. 1/2, pp 97 -  abstract 121, ISSN 0250-0868

Abstract

We addressed the question whether systemic administration of proteases may retard the progressive course of chronic renal failure. The rat model of subtotal nephrectomy (5/6-Nx) was used. A fixed combination of trypsin, bromelin and rutosid was administered. 5/6-NX male Wistar rats were randomized into control (C, n=7, 2 ml of .9 % NaCl/day i.p.) and test group (P, n=7, treated with 12 mg of Phlogenzym in 2 ml of .9 % NaCl/day i.p.). After 6 weeks the actively treated group showed lower mean plasma creatinine levels, higher clearance of creatinine and lower proteinuria as compared to placebo group. BUN level did not change. Renal morphology revealed that the percentual volume fraction of interstitial tissue in renal cortex, the number of infiltrating mononuclear cells and the amount of collagen fibres was lower in the protease treated group. Activities of lysosomal proteases (cathepsin L, B, and H), which are decreased in the remnant kidney model, increased significantly in the Phlogenzym treated group, both in isolated glomeruli and tubules. Decreased formation of cytokines was reflected by the lower urinary output of TGF-b1.

Conclusion

For the first time, evidence was given that protease treatment is beneficial in a non-immune mediated renal disease. Proteolytic enzymes ameliorate the development of tubulo-interstitial fibrosis, and progression of chronic renal failure in the model of 5/6 nephrectomised rats probably by diminishing the cytokine formation in renal tissue and its release from infiltrating cells.

Nieren-und Hochdruckkrankheiten, 1997, Jahrgang 26, Nr. 6, pp. 277 - 281;