Acute infusion of amphotericin B: Proximal tubular effects

Abstract

Summary: Electron microprobe analysis (EMPX) was employed to determine the alterations in intracellular electrolyte concentrations in proximal tubular cells resulting from acute treatment with amphotericin B. Concurrent clearance data confirmed a drop in glomerular filtration rate (GFR) in the rats treated with amphotericin B infusion (1 mg/kg per h) compared to control animals infused with saline (0.69 ± 0.11 vs 1.27 ± 0.08 mL/min per 100 g; P < 0.001). Measurement of intracellular electrolytes in proximal tubular cells in mmol/kg wet weight by EMPX demonstrated no difference in Na (16.2 ± 0.6 vs 17.2 ± 0.5) or K (129.7 ± 2.1 vs 131.3 ± 2.0). Intracellular Rb accumulation following acute infusion was significantly reduced in the amphotericin B treated animals (3.9 ± 0.4 vs 6.6 ± 0.4; P < 0.0001), suggestive of a reduction in basolateral Na‐K ATPase activity. These results do not support the tenet that amphotericin B causes a generalized increase in epithelial cell membrane ionic permeability, nor direct tubular toxicity in the doses and time frame studied. Rather, they suggest that a primary reduction in GFR results acutely in a load‐dependent decrease in proximal tubular Na transport.