Prevalence of nephrotoxicosis associated with a four-hour saline solution diuresis protocol for the administration of cisplatin to dogs with naturally developing neoplasms

Gregory K. Ogilvie From the Comparative Oncology Unit, Department of Clinical Sciences (Ogilvie, Straw, Jameson, Walters, Lafferty, Henkel, Withrow) and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Rodney C. Straw From the Comparative Oncology Unit, Department of Clinical Sciences (Ogilvie, Straw, Jameson, Walters, Lafferty, Henkel, Withrow) and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Vicki J. Jameson From the Comparative Oncology Unit, Department of Clinical Sciences (Ogilvie, Straw, Jameson, Walters, Lafferty, Henkel, Withrow) and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Lisa M. Walters From the Comparative Oncology Unit, Department of Clinical Sciences (Ogilvie, Straw, Jameson, Walters, Lafferty, Henkel, Withrow) and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Mary Lafferty From the Comparative Oncology Unit, Department of Clinical Sciences (Ogilvie, Straw, Jameson, Walters, Lafferty, Henkel, Withrow) and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Barbara E. Powers From the Comparative Oncology Unit, Department of Clinical Sciences (Ogilvie, Straw, Jameson, Walters, Lafferty, Henkel, Withrow) and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Susan E. Henkel From the Comparative Oncology Unit, Department of Clinical Sciences (Ogilvie, Straw, Jameson, Walters, Lafferty, Henkel, Withrow) and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Stephen J. Withrow From the Comparative Oncology Unit, Department of Clinical Sciences (Ogilvie, Straw, Jameson, Walters, Lafferty, Henkel, Withrow) and Radiological Health Sciences (Powers), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Summary:

We evaluated the development of nephrotoxicosis in 64 dogs with malignant neoplasia given cisplatin during 4-hour saline solution diuresis. Cisplatin (70 mg/m2 of body surface area, iv, q 21 d) was given to 8 dogs once, 22 dogs twice, 9 dogs 3 times, and 25 dogs 4 times. For each treatment, cisplatin was given over a 20-minute period after saline (0.9% NaCl) solution was administered iv for 3 hours at a rate of 25 ml/kg/h. After cisplatin infusion, saline solution diuresis was continued at the same rate for 1 hour. Before each treatment with cisplatin, the dogs were evaluated by conducting a physical examination, cbc, and analysis of serum urea nitrogen and creatinine concentrations, and in most cases, serum phosphorus concentration and urine specific gravity were determined. Exogenous creatinine clearance also was evaluated in 8 dogs prior to 1 (n = 8), 2 (n = 8), 3 (n = 6), and 4 (n = 4) treatments. Five (7.8%) of 64 dogs developed clinically evident renal disease after two (n = 3) and three (n = 2) doses of cisplatin. Two of the 5 dogs had preexisting diseases of the urinary tract prior to the start of treatment. Survival time in dogs that developed renal disease (median, 114 days; range, 26 to 273 days) was similar to that of all dogs in this study (median, 145 days; range, 5 to 586 days), with 30 dogs still alive at the conclusion of the study. Three of the 5 dogs that developed renal disease were alive at the conclusion of the study, 1 died of tumor-related causes, and another died as a direct result of nephrotoxicosis. There was a significant (P < 0.05) decrease in median neutrophil counts and a significant (P < 0.05) increase in median creatinine concentrations prior to the third and fourth treatments, compared with pretreatment values. Therefore, the 4-hour saline solution diuresis protocol used in this study to administer up to 4 doses of cisplatin appeared to be effective in preventing clinically apparent nephrotoxicosis in dogs with tumors and without preexisting urinary tract disease.

Summary:

We evaluated the development of nephrotoxicosis in 64 dogs with malignant neoplasia given cisplatin during 4-hour saline solution diuresis. Cisplatin (70 mg/m2 of body surface area, iv, q 21 d) was given to 8 dogs once, 22 dogs twice, 9 dogs 3 times, and 25 dogs 4 times. For each treatment, cisplatin was given over a 20-minute period after saline (0.9% NaCl) solution was administered iv for 3 hours at a rate of 25 ml/kg/h. After cisplatin infusion, saline solution diuresis was continued at the same rate for 1 hour. Before each treatment with cisplatin, the dogs were evaluated by conducting a physical examination, cbc, and analysis of serum urea nitrogen and creatinine concentrations, and in most cases, serum phosphorus concentration and urine specific gravity were determined. Exogenous creatinine clearance also was evaluated in 8 dogs prior to 1 (n = 8), 2 (n = 8), 3 (n = 6), and 4 (n = 4) treatments. Five (7.8%) of 64 dogs developed clinically evident renal disease after two (n = 3) and three (n = 2) doses of cisplatin. Two of the 5 dogs had preexisting diseases of the urinary tract prior to the start of treatment. Survival time in dogs that developed renal disease (median, 114 days; range, 26 to 273 days) was similar to that of all dogs in this study (median, 145 days; range, 5 to 586 days), with 30 dogs still alive at the conclusion of the study. Three of the 5 dogs that developed renal disease were alive at the conclusion of the study, 1 died of tumor-related causes, and another died as a direct result of nephrotoxicosis. There was a significant (P < 0.05) decrease in median neutrophil counts and a significant (P < 0.05) increase in median creatinine concentrations prior to the third and fourth treatments, compared with pretreatment values. Therefore, the 4-hour saline solution diuresis protocol used in this study to administer up to 4 doses of cisplatin appeared to be effective in preventing clinically apparent nephrotoxicosis in dogs with tumors and without preexisting urinary tract disease.

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