Urinary adenosine excretion in patients receiving amphotericin B

Intravenous amphotericin B (AMB) administration in animals causes renal vasoconstriction, ischemia, and oliguria that may result in irreversible renal injury; the mechanism of AMB nephrotoxicity may be similar in human beings. Adenosine is excreted in urine by the ischemic kidney. We hypothesized that adenosine excretion and oliguria would be a marker for patients who later would manifest AMB-associated renal insufficiency and that pre-AMB saline administration (which ameliorates AMB nephrotoxicity) would negate the change in adenosine excretion and urine output.

Twenty hospitalized patients being treated at the direction of their attending physician and who were receiving AMB (15 to 75 mg intravenously) had urine collected for 1 hour before and for 2 hours during AMB infusion. Eleven patients received normal saline solution (500 ml intravenously) before the AMB infusion; the other nine formed the comparator group. An aliquot of each urine collection was precipitated with perchloric acid to remove protein and cellular elements and centrifuged, and the supernatant was assayed for adenosine by using high-pressure liquid chromatography.

Infusion of AMB was associated with a decrease in mean urine output both in patients who received saline solution (245 before versus 149 ml/hr during AMB infusion, p = 0.04) and in patients in comparator group (139 versus 89 ml/hr, p = 0.027). The mean urinary adenosine excretion was unchanged in the saline-loaded group (0.1354 before versus 0.1255 mmol/hr during drug infusion, p = 0.25) and was decreased in the comparator group (0.2276 versus 0.1127 mmol/hr, p = 0.01). Development of renal insufficiency did not correlate with the change in urine output or adenosine excretion.

AMB infusion in human beings results in decreased urine output and decreased adenosine excretion. The latter effect is prevented by a pre-AMB saline load. The changes in urine output and adenosine excretion are not predictive of the development of renal insufficiency.