Prevention of cisplatin-induced nephrotoxicosis in dogs, using hypertonic saline solution as the vehicle of administration

S. Dru Forrester From the Departments of Small Animal Clinical Sciences (Forrester, Fallin), Pathobiology (Saunders), and Biomedical Sciences (Kenny), Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.

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Edward A. Fallin From the Departments of Small Animal Clinical Sciences (Forrester, Fallin), Pathobiology (Saunders), and Biomedical Sciences (Kenny), Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.

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Geoffrey K. Saunders From the Departments of Small Animal Clinical Sciences (Forrester, Fallin), Pathobiology (Saunders), and Biomedical Sciences (Kenny), Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.

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James E. Kenny From the Departments of Small Animal Clinical Sciences (Forrester, Fallin), Pathobiology (Saunders), and Biomedical Sciences (Kenny), Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.

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Summary

We determined whether administration of cisplatin in hypertonic saline solution would prevent significant decrease in renal function, as measured by exogenous creatinine clearance, in healthy dogs. A single dose of cisplatin (70 mg/m2 of body surface) was mixed in 3% saline solution and was infused IV (6.5 ml/kg of body weight) over a 20-minute period to 6 healthy dogs. Exogenous creatinine clearance was determined prior to treatment of dogs with cisplatin and again on days 3 and 21 after administration of cisplatin. All 6 dogs vomited at least once within 12 hours of treatment with cisplatin; however, clinically important changes in appetite, body weight, or hydration status were not apparent during the 21-day study. Although mean values for exogenous creatinine clearance decreased from baseline on days 3 and 21, changes were not significantly different. Renal histologic lesions included mild, chronic, lympho-plasmacytic interstitial nephritis in 5 dogs, and presumably, were unrelated to treatment with cisplatin. Mild renal tubular atrophy (n = 2) and tubular necrosis (n = 1) may have developed secondary to treatment with cisplatin. Results of this study indicated that administration of a single dose of cisplatin in 3% saline solution to healthy dogs was not associated with significant decrease in glomerular filtration rate. This is a convenient protocol for administering cisplatin; however, additional study is required before it can be recommended for clinical patients, especially those with preexisting renal disease or those receiving multiple doses of cisplatin.

Summary

We determined whether administration of cisplatin in hypertonic saline solution would prevent significant decrease in renal function, as measured by exogenous creatinine clearance, in healthy dogs. A single dose of cisplatin (70 mg/m2 of body surface) was mixed in 3% saline solution and was infused IV (6.5 ml/kg of body weight) over a 20-minute period to 6 healthy dogs. Exogenous creatinine clearance was determined prior to treatment of dogs with cisplatin and again on days 3 and 21 after administration of cisplatin. All 6 dogs vomited at least once within 12 hours of treatment with cisplatin; however, clinically important changes in appetite, body weight, or hydration status were not apparent during the 21-day study. Although mean values for exogenous creatinine clearance decreased from baseline on days 3 and 21, changes were not significantly different. Renal histologic lesions included mild, chronic, lympho-plasmacytic interstitial nephritis in 5 dogs, and presumably, were unrelated to treatment with cisplatin. Mild renal tubular atrophy (n = 2) and tubular necrosis (n = 1) may have developed secondary to treatment with cisplatin. Results of this study indicated that administration of a single dose of cisplatin in 3% saline solution to healthy dogs was not associated with significant decrease in glomerular filtration rate. This is a convenient protocol for administering cisplatin; however, additional study is required before it can be recommended for clinical patients, especially those with preexisting renal disease or those receiving multiple doses of cisplatin.

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