Studies on nephrotoxicity of combined administration of kanamycin and sodium alginate

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It has recently been studied clinically and histologically to work out that administration of kanamycin in combination with sodium alginate solution given as a plasma expander develops acute renal failure. In this study, respiratopy activity of renal tissue and some enzyme activities in the tissue have been employed as indicators of tissue damage in addition to the routine indicators such as histological findings and blood urea nitrogen levels. Kanamycin was administered to the rats intramuscularly (500mg/kg body weight/day), and sodium alginate intraperitoneally (60ml of 0.4% solution/kg/day). No water was given to the rats in the whole experimental periods. Succinoxidase, glutaminase, alkaline phosphatase were the enzymes studied.Results1) Decrease in respiratory activity of renal tissue was observed 24 hours after the administration of kanamycin and sodium alginate. 48 hours after the administration course had started, respiratory activity of renal tissue from experimental animals was less than half of that from controls. Much less impairment was brought about by kanamycin or sodium alginate alone. 2) Decrease in the activities of glutaminase, succinoxidase and alkaline phosphatase were observed by combined administration. Such decrease in enzyme activities was noticed earlier and more seriously than impairment in respiratory activity. 3) Elevation of blood urea nitrogen level seems being correlated with renal impairment. 4) Histological examinations of kidneys administered with kanamycin and sodium alginate revealed complete destruction of tissue especially in the epithelium of proximal and distal tubules 48 to 72 hours after administration course had started, 5) In vitro addition of a comparable amount of kanamycin and sodium alginate to kidney homogenates did not cause inhibition of succinoxidase activity, whereas addition of kanamycin only caused 25% inhibition of O2 uptake. 6) Neither remarkable change in respiratory activity nor histological change of liver tissue was noticed even after 48 to 72 hours after the administration of kanamycin and sodium alginate to the rats.