EFFECT OF AMPHOTERICIN-B ON WATER AND UREA TRANSPORT IN THE INNER MEDULLARY COLLECTING DUCT

The clinical usefulness of amphotericin B (AMP-B) is limited by its ne phrotoxicity, as characterized by decreased RPF, decreased GFR, impair ed urinary acidification, and potassium excretion defects. Defects of renal concentrating ability have been noted, but the mechanisms respon sible for them have not been investigated. The chief objective of this research was to analyze directly the effect of AMP-8 on arginine-vaso pressin (AVP)- or dibutyrl cAMP (DcAMP)-stimulated water and urea tran sport of the inner medullary collecting duct (IMCD) obtained from rats by the in vitro microperfusion technique. AMP-B (10(-5) M) added to t he bath fluid in the absence of AVP did not impair the hydraulic condu ctivity (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 per iod 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 0.01) in a reversible ma nner when the drug was withdrawn from the bath. AMP-B also decreased A VP-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 0.001), and this effect was reversi ble after AMP-B was withdrawn from the bath (37.40 +/- 1.36; P < 0.001 ). However, when AMP-B was added to the both in the presence of DcAMP (10(-4) M), the values of Pu did not change significantly. When the ef fect of deoxycholate, the vehicle for AMP-B, was measured, Lp and Pu d ata were not modified. Thus, AMP-B in the peritubular fluid decreased the stimulatory action of AVP and DcAMP on water permeability and AVP- stimulated Pu in rat IMCD. Both mechanisms contribute to the nephrogen ic diabetes insipidus induced by AMP-B.