title: Potassium depletion potentiates amphotericin-B-induced toxicity to renal tubules.
abstract: Hypokalemia and potassium depletion are frequent complications of amphotericin B therapy. Both ischemic and gentamicin-induced renal failure is potentiated by potassium depletion; it is, therefore, possible that amphotericin B nephrotoxicity is similarly influenced. This study evaluated whether the acute nephrotoxic response to amphotericin B is potassium sensitive. Potassium-depleted and control rats were subjected to an acute intravenous infusion of either amphotericin B (AmB-K; AmB, n = 10 in each) or its vehicle (V-K, V; n = 6 in each). Potassium-depleted rats had both lower urinary daily excretion and lower plasma levels of potassium than control animals (0.1 +/- 0.0 vs. 2.1 +/- 0.2 mEq/day, p < 0.001, and 3.8 +/- 0.2 vs. 1.9 +/- 0.1 mEq/l, p < 0.001, respectively). In AmB and AmB-K groups, there were equivalent falls in glomerular filtration rate and renal blood flow, and a rise in renal vascular resistance, compared with V and V-K. In contrast, the AmB-K group showed a higher urinary excretion of sodium (AmB-K vs. AmB: 2.9 +/- 0.7 vs. 1.1 +/- 0.3 microEq/min; p < 0.05) and fractional excretion of Na (AmB-K vs. AmB: 1.6 +/- 0.4 vs. 0.6 +/- 0.1%; p < 0.05) in comparison to the AmB group. Neither of these parameters changed in either amphotericin B or vehicle-treated groups. These results suggest that potassium depletion does not influence the acute renovascular effects of amphotericin B but potentiates its tubular toxicity. This may have clinical implications since hypokalemia and potassium depletion are frequent complications of amphotericin B therapy.
authors.affiliation: Center for Clinical Pharmacology, University of Pittsburgh Medical Center, PA 15213-2582, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Bernardo
authors.forename: S
authors.initials: S
authors.lastname: Murakami
authors.forename: R A
authors.initials: RA
authors.lastname: Branch
authors.forename: R
authors.initials: R
authors.lastname: Sabra
mesh_terms: D000666:Amphotericin B / Q000009:adverse effects*; D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects*; D001835:Body Weight; D007275:Injections, Intravenous; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects*; D008297:Male; D011188:Potassium / Q000652:urine; D011191:Potassium Deficiency / Q000150:complications* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B; D012964:Sodium; D011188:Potassium