Effect of adenosine triphosphate, benidipine and their combinations on bevacizumab-induced kidney damage in rats.

BACKGROUND: Bevacizumab-induced vascular endothelial growth factor (VEGF) inhibition may lead to a decrease in adenosine triphosphate (ATP) levels, an increase in intracellular Na+ and Ca2+ concentrations and an increase in reactive oxygen species (ROS) generation, as well as to cell damage. OBJECTIVES: To investigate the biochemical and histopathological effects of ATP, benidipine and ATP in combination with benidipine on bevacizumab-induced kidney damage in rats. MATERIAL AND METHODS: Rats were divided into 5 treatment groups: bevacizumab (BVZ) alone, ATP + bevacizumab (ABVZ), benidipine + bevacizumab (BBVZ), ATP + benidipine + bevacizumab (ABBVZ), and healthy controls (HC). Adenosine triphosphate (25 mg/kg), benidipine (4 mg/kg orally), ATP (25 mg/kg) + benidipine (4 mg/kg), or saline were administered to albino Wistar rats. One hour after treatment, bevacizumab was injected at a dose of 10 mg/kg to induce kidney damage. Two doses of bevacizumab were delivered 15 days apart. Adenosine triphosphate + benidipine were administered once a day for 1 month. RESULTS: Malondialdehyde (MDA), total oxidant status (TOS), creatinine, and blood urea nitrogen (BUN) levels of the BVZ, BBVZ, ABVZ, ABBVZ, and HC groups were ranked from highest to lowest. Conversely, total glutathione (tGSH) and total antioxidant status (TAS) kidney tissue values were ranked from lowest to highest, respectively. Hemorrhage, tubular necrosis and grade 3 focal tubular atrophy were observed in the BVZ group. Atrophy and grade 2 necrosis were observed in the BBVZ group and atrophy and grade 1 necrosis were observed in the ABVZ group. Only grade 1 atrophy was observed in the ABBVZ group. CONCLUSIONS: Adenosine triphosphate reduced bevacizumab-induced renal toxicity significantly more effectively than benidipine. However, the combination of ATP + benidipine further reduced bevacizumab-induced renal toxicity relative to benidipine or ATP alone. These data indicate that ATP + benidipine might be a potential therapeutic strategy for the prevention of bevacizumab-induced renal toxicity.

Time dependant functional and morphological recovery of the kidney after relief of obstruction in patients with impacted ureteral stones.

OBJECTIVES: To assess the course of functional and morphological recovery of the kidney following the relief of obstruction with ureteral JJ stent in cases with unilateral impacted stones. MATERIALS AND METHODS: A total of 42 adult patients who were admitted to our clinic with unilateral obstructing impacted ureteral stones requiring JJ stent placement were included in the study. The course of functional recovery was assessed by evaluating the serum creatinine levels, renal resistive index (RRI) values and urinary levels of kidney injury molecule-1, neutrophil gelatinaseassociated lipocalin as well as microalbumin before at 1 day, 1 week and 4 weeks after JJ stent placement. Course of morphologic recovery was evaluated by evaluating the degree of hydronephrosis, kidney size, perirenal straining and ureteral diameter. RESULTS: Our results showed that all relevant parameters began to decrease after 24 hours and continue to normalize during 1 week evaluation; majority of these variables indicating the functional and morphological recovery were in normal range after 4 weeks. Decompression of the obstructed kidneys with JJ stent placement in patients with impacted ureteral stones was found to be effective enough with recovery of normal renal functional and morphological status after a minimum time period of 4 weeks. Morphological recovery of affected kidneys following JJ stenting was obtained with a significant difference between baseline and 1-month evaluation findings (p = 0.001, p < 001, p < 001, respectively). KIM-1 excretion began to decline to normal levels after 4 weeks (3.52 ± 0.99 ng/ml versus 2.84 ± 0.66 ng/ml, p < 0.001). The same findings were observed for the urinary excretion levels of NGAL, which normalized at the 1-month evaluation (604.55 ± 140.28 ng/ml versus 596.87 ± 80.17 ng/ml p = 0.895). Urinary microalbumin excretion levels however remained high even until 1-month follow-up with a statistically significant difference when compared with the normal excretion values (p < 0.001). There was a statistically significant difference in RRI values between baseline and 1-month follow-up findings in obstructed kidney (p < 0.001). CONCLUSIONS: Elective management of the obstructing impacted ureteral stone(s) will be safer with limited risk of infective complications after functional and morphological normalization in such kidneys following 4 weeks of JJ stent placement.