Experimental studies on the nephrotoxicity of amphotericin b in rats

The renal effects of amphotericin B alone and in combination with cyclosporin A, tobramycin, fosfomycin, D-glucaro-1,5-lactam and veraparmil were studied in rats. The parameter for nephrotoxicity were urinary loss of tubular cells and malatedehybrogenase, as well as creatinine clearance. Repeated intraperitoneal injections of amphotericin B led to an increase of urinary tubular cell elimination and malatedehyrogenase. After co-administration of amphotericin B and cyclosporin A, the urinary loss of tubular cells increased and creatinine clearance was reduced. A combination of amphotericin B and tobramycin reduced tubular cell elimination but the creatinine clearance improved. When verapamil was combined with amphotericin B, endogenous acatinine clearance increased, though the loss of tubular cells was elevated. Furthermore, fosfomycin reduced the loss of tubular cells and improved renal functional parameters in combination with amphotericin B. In addition, D-glucaro-1,5-lactam was found to reduce the urinary loss of tubular cells induced by amphotericin B.