Amphotericin B nephrotoxicity: increased renal resistance and tubule permeability

Two groups of rats received amphotericin-B (Amp). One group (AA) received a single acute dose of 1 mg/kg i.v. The second (CA) received 10 mg/kg i.p. daily for 4 days. In AA rats, measurements 1 to 5 hr after Amp were compared with their own preinfusion values. Inulin clearance, (CIn, 4.5 ml X min-1 X kg-1 per kidney pre vs. 1.3 post), renal plasma flow (RPF, 12.0 ml X min-1 X kg-1 vs. 7.4), and the estimated pressure in the glomerular capillaries (Pgc, 52 mm Hg vs. 40), were all significantly decreased while renal vascular resistance (5.2 mm Hg/ml vs. 12.0) was increased. Only 45% of the 3H-inulin injected into surface tubules was recovered in the urine as contrasted with 100% recovery before injection. This suggests that tubule permeability was increased, but there was no histologic evidence of renal tubule necrosis. Twenty-four hours after intravenous Amp, CIn and RPF returned to normal. Data from CA rats were compared with values from sham-treated pairfed (PF) control rats. Again, CIn (4.22 ml X min-1 X kg-1 in PF vs. 2.69 in CA), RPF (16.1 ml X min-1 X kg-1 vs. 8.3), and Pgc (48 mm Hg vs. 38) were decreased, and renal vascular resistance (4.9 mm Hg/ml vs. 8.0) was increased. The recovery of 3H-inulin in the urine was slightly, but significantly, decreased (96% vs. 83%). These findings demonstrate that Amp decreases renal function by at least two mechanisms. An increase in renal vascular resistance is most important, although increased tubule permeability with a "backleak" of tubule fluid also contributes to renal dysfunction, particularly after intravenous Amp.