الفهرس 
IntroductionOnly 14 pages are availabe for public view
Abstract
Cisplatin is an important anti-cancer medication used for treatment for variety of malignant tumors. The most important toxicity caused by cisplatin is nephrotoxicity. Cisplatin-induced nephrotoxicity still occurs despite intensive hydration, reduction in glomerular filtration occurs in in approximately 30% of patients including acute renal failure and chronic renal insufficiency.
Evidence that mannitol may have protective effect against cisplatin-induced nephrotoxicity is not clear. This is due to conflict showed by studies in animals and clinical trials. These trials have contradicting results that mannitol may or may not have protective effect against cisplatin-induced nephrotoxicity. Acetazolamide (ACTZ) and N-acetylcysteine (NAC) ameliorated Cisplatin-induced nephrotoxicity in rats. No study to date evaluated the protective effect of acetazolamide or NAC against cisplatin nephrotoxicity in humans.
Current study was conducted to evaluate both the efficacy and safety of ACTZ or NAC against cisplatin nephrotoxicity in humans compared to mannitol and to each other.
A total 52 patients receiving standard hydration measures for cisplatin were randomized to three groups: 20 patients receiving mannitol 20 % 100 ml half an hour before cisplatin and saline hydration, 15 patients receiving acetazolamide acetazolamide 250 mg half an hour before cisplatin with saline hydration and 17 patients receiving NAC (600 mg every 12 hours) for 4 doses beginning 24 hours before cisplatin with saline hydration. Patients` kidney function was monitored using serum creatinine, creatinine clearance and blood urea nitrogen; kidney injury was assessed using RIFLE criteria. Patients` liver function tests and hematological parameters were also measured and monitored.
There was a statistically significant protective effect of either ACTZ or NAC groups compared to mannitol group on kidney function. This was apparent in laboratory results as differences by time between three groups in creatinine level, creatinine clearance values and BUN levels were statistically significant with P-values 0.045, 0.012 and 0.016 respectively. However, no statistically significant difference occurred between either ACTZ or NAC groups compared to mannitol group regarding liver function tests or hematological parameters. Liver function was monitored using AST and ALT levels and there were no statistically significant differences between the three groups with P-values 0.369 and 0.182 respectively. Hematological parameters were monitored using hemoglobin, total leucocytes count and platelets while there were no statistically significant differences between the three groups with P-values 0.479, 0.114 and 0.256 respectively. The intervention drugs did not show any increase in adverse drug effects compared to mannitol.
It can be concluded that acetazolamide or NAC may have nephroprotective effect on cisplatin-induced nephrotoxicity which need to be confirmed in large multicenter randomized clinical trials. Both NAC and ACTZ medications showed comparable effect on creatinine clearance and blood urea nitrogen. By using RIFLE criteria it was found that number of patients developing injury state was increasing in mannitol group but in contrary was decreasing in both ACTZ group and NAC but was not statistically significant.
The number of patients requiring dose reduction due to decrease in kidney function was higher in mannitol group than both ACTZ group and N-acetylcysteine. There was no statistically significant difference between the three groups regarding adverse effects but leucopenia and peripheral neuropathy was highest in mannitol group while oral mucositis was highest in NAC group.