Evaluation of the results of sodium fumarate, furosemide, and mannitol on the initiation and outcome of renal warm ischemia in an experimental study

While performing surgical treatment of the localized form of renal cell cancer by means of open or laparoscopic partial nephrectomy, renal warm ischemia is an important issue. Using renal warm ischemia allows to prevent parenchymal bleeding, to optimize conditions for resection of the tumor and to increase significantly the efficiency of hemostasis. However, an important problem is the probability of ischemic hypoxic damage of the remaining part of the kidney tissue during renal warm ischemia and renal functional impairment in the postoperative period. Aim. To compare nephroprotective activity of sodium fumarate, mannitol 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 №2 included the rabbits in which renal artery was not clamped. For the animals from the trial groups (№3-№10) the experimental model of 30- and 60-minute renal warm ischemia was used. In groups №3 and №4 no drugs were provided. Other rabbits undergone renal warm ischemia with a protection by sodium fumarate (groups №5 and №6 - 1,5 ml/kg IV), lasix (groups №7 and №8 - 3,0 mg/kg IV) and mannitol (№9 and №10 - 1,0 g/kg IV). The influence of renal warm ischemia on the renal tissue ultrastructure and the levels of NGAL, Cystatin-C and creatinine in blood and urine were studied. Results. During experimental pharmacologically uncorrected 30-minute renal warm ischemia in animals, edema of the terminal part of microvilli of the proximal tubules’ epithelium, an 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 tubules, as well as sharp peak-like increase of NGAL and cystatin-C in blood and urine were observed. Increasing the time of ischemia up to 60 minutes was accompanied by more severe disturbances. In groups where sodium fumarate, lasix and mannitol were used the observed ultrastructural disturbances were expressed to lesser extent, whereas sodium fumarate demonstrated the best nephroprotective activity. After using mannitol the severity of disturbances was less than in the groups where mannitol, lasix or sodium fumarate were not given. Lasix and sodium salt of fumaric acid showed a higher nephroprotective activity. The best results were received in the animals received sodium fumarate. Conclusions. The studied drugs provided a nephroprotective effect regarding ischemia of rabbit kidney. The effect of sodium fumarate was the most pronounced, followed by furosemide and, to a lesser extent, mannitol. Use of sodium fumarate allows to protect and stimulate the kidney tissue effectively during oxygen deprivation under ischemic state.

renal warm ischemia, partial nephrectomy, ischemic hypoxic damage, pharmacological nephroprotection, antihypoxants, sodium fumarate