FOSCARNET ALTERS ANTIDIURETIC HORMONE-MEDIATED TRANSPORT

Therapy with foscarnet is associated with acute renal failure, Prior s tudies have emphasized foscarnet's proximal tubular toxicity, but ther e have been isolated reports of foscarnet-induced nephrogenic diabetes insipidus. As a phosphate analog, foscarnet is a competitive inhibito r of NaPO4 cotransport, However, foscarnet's effect on antidiuretic ho rmone (ADH)-induced transport has not been previously investigated, We studied foscarnet's modulation of transport in the toad urinary bladd er. Foscarnet at 10 mu M to 10 mM did not alter basal water or urea fl ux Urea transport induced by a maximal dose of ADH (24 mIU/ml) was inh ibited by 0.1 to 5.0 mM foscarnet. In tissues challenged with 0.5 to 1 .0 mIU of ADH per ml, 1.0 to 10 mM foscarnet increased water flow but did not alter urea flux Foscarnet also increased water flow induced by 1.0 to 10 mu M forskolin. In tissues pretreated with 10 mu M naproxen , foscarnet did not alter water flow induced by 0.5 to 1.0 mIU of ADH per ml or forskolin. These results indicate that foscarnet stimulates water flow induced by 0.5 to 1.0 mIU of ADH per mi at a site proximal to that of the generation of cyclic AMP and inhibits urea flux induced by a maximal dose of ADH at a separate site. In humans, foscarnet nep hrotoxicity is likely not limited to the proximal nephron, but extends to the collecting duct. Patients receiving foscarnet should be closel y monitored for disorders of urinary concentration.