Comparative Study of Sodium Fumarate, Mannitole and Furosemide Concerning Renal Warm Ischemia in Rabbits

While performing surgical treatment of the localized form of renal cell cancer by means of open or laparoscopic kidney resection, renal warm ischemia (RWI) is becoming the necessary aspect of the intervention. Using RWI allows to prevent parenchymal bleeding, to optimize operative conditions, to increase significantly the efficiency of hemostasis. However, an important problem is the probability of ischemic hypoxic damage of the secured part of the kidney tissue during RWI and renal functional impairment in the postoperative period. Aim of the study - comparative study of nephroprotective activity of sodium fumarate, mannitole and furosemide using experimental model of 30- and 60-minute renal warm ischemia in rabbits. Materials and methods: The experiments were carried out on 360 conventional male-rabbits of the "Chinchilla" breed weighed 2,6 +/- 0,3 kg which were allocated into 10 groups. The control group.1 included intact animals, the control group No2 included the rabbits having been operated on without clamping the renal artery. Animals from the trial groups (No3-No10) were given the experimental model of 30- and 60-minute RWI. In groups No3 and No4 medication was not provided. Other rabbits were performed renal warm exsanguination on the background of sodium fumarate (groups No5 and No6 - 1,5 ml/kg IV), lasix (groupsNo7 and No8 - 3,0 mg/kg IV) and mannitole (No9 and No10 - 1,0 g/kg IV). There was studied the effecct of RWI on the kidney tissue ultrastructure and the levels of NGAL, cystatin-C and creatinine in blood and urine. Results: Experimental pharmacologically non-corrected 30-minute RWI in trial animals induced swelling and edema of the final part of microvilli of the proximal tubules epithelium, increase of lysosome number in the hyaloplasm of epithelial cells, appearance of flaky content of medium electronic density in the lumens of distal tubules and collecting tubes, as well as sharp peak-like increase of NGAL and cystatin-C in blood and urine. Increasing the time of exsanguination up to 60 minutes was accompanied by the growth of severity and scales of the observed disturbances. In groups where sodium fumarate, lasix and mannitole were used the observed ultrastructural disturbances were the least pronounced, whereas sodium fumarate demonstrated the best nephroprotective activity. In case of using mannitole the intensity of the observed disturbances was less than in the groups where mannitole, lasix or sodium fumarate were not provided. Lasix and sodium salt of fumaric acid showed a higher nephroprotective activity. The best results were received in the animals protected by sodium fumarate. Conclusions: The studied medications produced a nephroprotective effect regarding renal ischemia of rabbits, sodium fumarate in the greatest degree, furosemide - less and mannitole the least. Use of sodium fumarate allows to protect and stimulate the kidney tissue maximum effectively during oxygen deprivation of the ischemized organ.