EFFECT OF CYCLOSPORINE ON URINARY PROSTANOID EXCRETION, RENAL BLOOD FLOW, AND GLOMERULOTUBULAR FUNCTION

Abstract

The clinical usefulness of cyclosporine (CsA) in organ transplantation and autoimmune diseases is limited by its intrinsic nephrotoxicity. The mechanism of this renal impairment was examined utilizing an animal model in which male Sprague-Dawley rats were administered oral CsA in doses of 25, 37.5, and 50 mg/kg/day for 7 days and 50 mg/kg/day for 2, 4, and 7 days. Urinary thromboxane B₂ (TXB₂) excretion increased from 30.6± 2.3 to 60.8±4.4 ng/24 hr I2 and 6-keto-prostaglandin F_1α excretion increased twofold, although plasma levels of all 3 prostanoids did not vary from cpntrols. Functional changes included decreases in the relative renal blood flow of 53% P<0.05, and the clearance of creatinine and urea of 46% and 42%, respectively on day 7 of treatment, while renal