ACUTE INFUSION OF AMPHOTERICIN-B - PROXIMAL TUBULAR EFFECTS

Electron microprobe analysis (EMPX) was employed to determine the alte rations in intracellular electrolyte concentrations in proximal tubula r cells resulting from acute treatment with amphotericin B. Concurrent clearance data confirmed a drop in glomerular filtration rate (GFR) i n the rats treated with amphotericin B infusion (1 mg/kg per h) compar ed 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 electro lytes in proximal tubular cells in mmol/kg wet weight by EMPX demonstr ated 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 anim als (3.9 +/- 0.4 vs 6.6 +/- 0.4; P < 0.0001), suggestive of a reductio n in basolateral Na-K ATPase activity. These results do not support th e tenet that amphotericin B causes a generalized increase in epithelia l cell membrane ionic permeability, nor direct tubular toxicity in the doses and time frame studied. Rather, they suggest that a primary red uction in GFR results acutely in a load-dependent decrease in proximal tubular Na transport.