Renal arterial infusion of cyclophosphamide in dogs

Cyclophosphamide, a nitrogen mustard derivative, has been reported to induce antidiuresis in man and water diuresis in dogs. In order to determine whether the drug acts directly on the kidney, we have infused the drug into one renal artery of hydropenic dogs and compared the responses with those observed following i.v. administration. Renal artery infusion of two different doses in ten dogs induced no unilateral or bilateral, hemodynamic or excretory responses. Intravenous administration of similar doses (16 mg/min for 120 to 160 min) in five dogs induced a progressive increase in the clearance of para-aminohippurate (PAH) (P less than 0.05), creatinine and urea (P less than 0.01), and a natriuresis and kaliuresis (P less than 0.05). The excretion of phosphate increased but was not statistically significant. There was a significant decrease (P less than 0.01) in the clearance of free water. The lack of response to intrarenal infusion of a drug which acts systemically to alter renal function is unusual. Possible explanations are inactivation of drug by renal tissue or rapid excretion by the kidney. In either case, removal rate must approximate renal blood flow in order to prevent the systemic response to the drug.