Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 49, Issue 9, Pages 3784-3788Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.49.9.3784-3788.2005
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- NCRR NIH HHS [M01 RR-00997] Funding Source: Medline
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The present study assessed potential subclinical markers of amphotericin B (AmB)-related nephrotoxicity and infusion-related reactions (IRR). Subjects were pretreated with diphenhydramine and acetaminophen and received a 500-ml bolus infusion of 0.9% sodium chloride prior to each effective renal plasma flow (ERPF) assessment. ERPF was measured before and after administration of a single 0.25-mg/kg intravenous AmB dose using technetium-99m mercaptoacetyltriglycine. Blood was collected before and 3 h after AmB infusion for tumor necrosis factor alpha (TNF-alpha) and interleuldn-1 beta (IL-1 beta) plasma concentrations. Overnight 12-h urine collections were performed before administration of AmB and for 2 nights after administration of AmB and analyzed for alpha and pi glutathione-S-transferases (GST alpha and GST pi, respectively) and N-acetyl-beta-D-glucosaminidase (NAG). Six men and six women with mean standard deviation (SD) ages of 24.8 +/- 5.3 and 28.0 +/- 8.5 years, respectively, were studied. Baseline serum creatinine values were within the normal range and were unaltered after administration of AmB. The mean SD decrease in ERPF after administration of AmB was significant (P < 0.05) in males (15.7 +/- 8.1%) but not females (9.5 +/- 14.0%). The GST pi and GST alpha indices increased significantly (P < 0.05) by two to fourfold and returned to baseline in males but were unaltered in females. NAG indices were unaffected by AmB. Six patients experienced an IRR that was associated with increased TNF-alpha (P < 0.05) but not IL-1 beta (P = 0.09). These results suggest a potential sex-related difference in AmB-induced nephrotoxicity and provide a rationale for use of ERPF, urine GST, and TNF-alpha as subclinical markers of polyene-induced toxicity.
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