Protective Effect of Forced Hydration with Isotonic Saline, Potassium Chloride and Magnesium Sulfate on Cisplatin Nephrotoxicity: An Initial Evaluation

Background: Nephrotoxicity is one of the major side-effects of cisplatin that has been seen in about 20% of treated patients. The aim of this study was to assess the effectiveness of a forced hydration protocol comprised of isotonic saline, potassium chloride (KCl) and magnesium sulfate (MgSO4) on prevention of cisplatin nephrotoxicity. Methods: This cross sectional prospective study was performed on cancer patients treated in Shafa Hospital, Ahvaz, Iran from November 2009 to March 2010. The patients were under at least 50 mg/m2 cisplatin. All patients received 1000 mL isotonic saline plus 20 mEq of KCl and 2 g of MgSO4 during 2-3 hours before, and 500 mL of the same solution over the two hours after administration of cisplatin. The prescribed dose of the solution was to the extent facilitating a urine flow of at least 100 mL/h for two hours prior to chemotherapy and 2 hours post-chemotherapy. Cisplatin nephrotoxicity was defined as an increase in the SCr equal or over 0.5 mg/dL during the 5 day follow-up post-chemotherapy. Results: A total of 76 patients (48 men and 28 women with mean (SD) age of 51.0 (17.6) years) were studied. Mean cumulative cisplatin dose was 86.7 (43.1) mg/m2. Hypokalemia and hypomagnesemia were not observed in any patient. Cisplatin nephrotoxicity (increase of creatinine) was developed in 5 patients (6.6%). The mean dose of cisplatin in patients with and without nephrotoxicity was 83 and 86.97 mg respectively which showed no significant difference between them (P = 0.8). Conclusion: The new protocol was able to decrease the rate of cisplatin nephrotoxicity from about 20% to 6.6%. Further case control studies with larger sample sizes are recommended to evaluate the effectiveness of this protocol.   How to cite this article: Beladi Mousavi SS, Hossainzadeh M, Khanzadeh A, Hayati F, Beladi Mousavi M, Zeraati AA, et al. Protective Effect of Forced Hydration with Isotonic Saline, Potassium Chloride and Magnesium Sulfate on Cisplatin Nephrotoxicity: An Initial Evaluation. Asia Pac J Med Toxicol 2013;2:136-9

The protective effect of theophyline in cisplatin nephrotoxicity

Cisplatin is a potent and a major anti-neoplastic drug in the treatment of a broad spectrum of malignancies. However, its clinical use is limited by renal tubular dysfunction that occurs in a significant percent of patients. The aim of the present study was to evaluate the possible protective effect of theophyline in the prevention of cisplatin-induced nephrotoxicity. The trial design was prospective, randomized, double-blinded and placebo controlled. Chemotherapeutic patients who received cisplatin at a dosage of at least 50 mg/m 2 alone or in combination with other chemotherapy agent(s) were included in the study. There were a total of 76 patients who were randomly divided into two groups. In group 1 (n = 38), placebo was advised; in group 2 (n = 38), patients received 4 mg/kg aminophyline as an intravenous loading dose, followed by theophyline in a dose of 200 mg three times daily orally for four consecutive days. The placebo group had 22 males and 16 females and the theophyline group had 26 males and 12 females. The mean age was 51 ± 17.6 years and the mean dose of cisplatin was 86.71 ± 43.18 mg. The prevalence of cisplatin nephrotoxicity in groups 1 and 2 was 7.9 and 5.3%, respectively, and the difference was not significant (P = 1). In addition, there was no significant association of cisplatin nephrotoxicity with age (P = 0.1), gender (P = 0.64) and mean dose of cisplatin (P = 0.8). These results indicate that prophy-lactic application of aminophyline and theophyline does not have a protective effect against cisplatin nephrotoxicity