Comparison of two saline loading protocols for preventing nephrotoxicosis associated with high-dose cisplatin

Cisplatin is an antineoplastic drug used to treat malignant tumors in human beings and dogs. Nephrotoxicosis was initially considered dose limiting. The use of saline loading and hypertonic saline administration protocols allowed dose escalation, reduced nephrotoxicosis, and increased remission rates in the treatment previously poorly responsive malignant tumors in human beings.

A pilot study was performed to determine efficacy of 4-hour saline loading in providing renal protection for dogs receiving high-dose cisplatin (150 mg/m² IV). Two beagles were saline loaded (25 ml/kg/hr of 0.9% NaCI, IV) for 4 hours and infused with cisplatin (150 mg/m²). We demonstrated that high-dose cisplatin (150 mg/m² IV) can be administered to dogs without biochemical evidence of acute nephrotoxicosis; however gastrointestinal toxicoses (fibrinonecrotic enteritis) and severe myelosuppression (leukopenia) were incompatible with patient survival and therefore, dose limiting. In another study we compared efficacy of hypertonic saline with normal saline in preventing nephrotoxicosis associated with administration of high-dose cisplatin (90 mg/m² IV) to dogs. In this study we demonstrated that a single IV dose of cisplatin (90mg/m²) can be administered to dogs in normal saline (0.9%) or hypertonic saline (7%) in combination with 4 hour saline loading (25 ml/kg/hr) without evidence of reduced renal function as measured by exogenous creatinine clearance. Platelet numbers were significantly increased in dogs that received cisplatin in hypertonic saline.

Nephrotoxicosis was not dose limiting in either study. Future studies should attempt to determine the efficacy and toxicoses of multiple doses of cisplatin (90 mg/M² administered in hypertonic saline to tumor bearing dogs.