Synergistic nephrotoxicity of amphotericin B and cortisone acetate in mice

Striking mortality in mice receiving amphotericin B and cortisone acetate concomitantly prompted studies to characterize the toxic interaction of these two drugs further. Adult female CD-1 mice received daily injections of cortisone acetate (0--50 mg/kg subcutaneously) and/or amphotericin B (0--12.5 mg/kg intraperitoneally) in a checkerboard combination dosage pattern for 30 days. Dosages of amphotericin B and cortisone acetate that produced little or no mortality individually produced significant (P less than 0.005) mortality in combination. Light and electron microscopic studies of sections of brain, heart, lung, adrenal gland, liver, and kidney revealed only renal lesions. These appeared within six days, were dose-related in severity, and were not produced by either drug alone. The lesions consisted of focal swelling of proximal, distal, and collecting tubular cells which progressed to necrosis and intraluminal cast formation. These findings may be relevant to the development of nephrotoxicity in patients treated simultaneously with amphotericin B and corticosteroids.