title: Mechanisms of amphotericin B-induced reduction of the glomerular filtration rate: a micropuncture study.
abstract: Amphotericin B infusions cause acute reductions in renal plasma flow and glomerular filtration rate. The exact mechanism by which these changes occur has not been identified fully, nor have the effects of the drug on the renal microcirculation been studied adequately. In this study, we examined the effect of intrarenal amphotericin B infusions (0.05 mg/kg/min) on glomerular hemodynamics in the anesthetized rat. Amphotericin B did not affect systemic blood pressure and slightly increased hematocrit (5%), but significantly decreased renal blood flow and glomerular filtration rate by 40 and 35%, respectively. Glomerular micropuncture revealed decreases in single nephron plasma flow and glomerular filtration rate (from 142 +/- 12 to 89 +/- 14 and from 35.3 +/- 2.2 to 22.8 +/- 2.8 nl/min, respectively). These changes were due to significant increases in pre- and postglomerular resistances (from 1.91 +/- 0.17 to 3.95 +/- 0.38 and from 1.30 +/- 0.10 to 2.08 +/- 0.12 10(10) dyn.sec.cm-5, respectively), and to a significant decrease in the glomerular capillary ultrafiltration coefficient which fell from 0.043 +/- 0.008 to 0.032 +/- 0.009 nl/(sec.mm Hg). These results provide further insight into the mechanisms of the acute renal effects of amphotericin B, and suggest possible mediators that may be involved in these effects.
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: R
authors.initials: R
authors.lastname: Sabra
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: R A
authors.initials: RA
authors.lastname: Branch
authors.forename: K F
authors.initials: KF
authors.lastname: Badr
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D005246:Feedback; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects; D008297:Male; D011677:Punctures; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000666:Amphotericin B