Effect of amphotericin B on water and urea transport in the inner medullary collecting duct

Abstract

The clinical usefulness of amphotericin B (AMP-B) is limited by its nephrotoxicity, as characterized by decreased RPF, decreased GFR, impaired urinary acidification, and potassium excretion defects. Defects of renal concentrating ability have been noted, but the mechanisms responsible for them have not been investigated. The chief objective of this research was to analyze directly the effect of AMP-B on arginine-vasopressin (AVP)- or dibutyrl cAMP (DcAMP)-stimulated water and urea transport of the inner medullary collecting duct (IMCD) obtained from rats by the in vitro microperfusion technique. AMP-B (10(-5) M) added to the bath fluid in the absence of AVP did not impair the hydraulic conductivity (Lp) and the urea permeability (Pu) of rat IMCD. AMP-B (10(-5) M) added to the bath fluid decreased the AVP-stimulated Lp (x 10(-6) cm/s.atm) of rat IMCD from 19.41 +/- 2.19 to 10.00 +/- 1.39 (P < 0.001), and the reversibility of its action was observed during a third period when Lp increased to 19.80 +/- 2.19 (P < 0.001) after the initial conditions were restored. In addition, AMP-B reduced DcAMP-stimulated Lp from 20.95 +/- 1.75 to 10.52 +/- 0.71 (P < 0.01) in a reversible manner when the drug was withdrawn from the bath. AMP-B also decreased AVP-stimulated Pu (x 10(-5) cm/s) when added to the bath fluid from 36.60 +/- 2.05 to 29.88 +/- 1.36 (P < 0.001), and this effect was reversible after AMP-B was withdrawn from the bath (37.40 +/- 1.36; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)