Foscarnet alters antidiuretic hormone-mediated transport.
Therapy with foscarnet is associated with acute renal failure. Prior studies have emphasized foscarnet's proximal tubular toxicity, but there have been isolated reports of foscarnet-induced nephrogenic diabetes insipidus. As a phosphate analog, foscarnet is a competitive inhibitor of NaPO4 cotransport. However, foscarnet's effect on antidiuretic hormone (ADH)-induced transport has not been previously investigated. We studied foscarnet's modulation of transport in the toad urinary bladder. Foscarnet at 10 microM to 10 mM did not alter basal water or urea flux. Urea transport induced by a maximal dose of ADH (24 mIU/ml) was inhibited 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 microM forskolin. In tissues pretreated with 10 microM 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 ml 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 nephrotoxicity is likely not limited to the proximal nephron, but extends to the collecting duct. Patients receiving foscarnet should be closely monitored for disorders of urinary concentration.
Hoch
B S
BS
Department of Medicine, Maimonides Medical Center, Brooklyn, New York 11219, USA.
Shahmehdi
S J
SJ
Louis
B M
BM
Lipner
H I
HI
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D002024:Bufo marinus; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D017245:Foscarnet / Q000494:pharmacology*; D066298:In Vitro Techniques; D009288:Naproxen / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014667:Vasopressins / Q000502:physiology*
D000998:Antiviral Agents; D016861:Cyclooxygenase Inhibitors; D010726:Phosphodiesterase Inhibitors; D014667:Vasopressins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D017245:Foscarnet; D009288:Naproxen; D015056:1-Methyl-3-isobutylxanthine