title: Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers.
abstract: Administration of sevoflurane in a circle absorption system generates Compound A, a nephrotoxin in rats. Reports examining the potential of Compound A to produce renal injury in humans have provided conflicting results. We tested the possibility that there is a threshold to Compound A-induced renal injury in humans and that, above this threshold, renal injury increases with increasing doses of Compound A. Eleven volunteers received 3% sevoflurane for 8 h at 2 L/min, and three volunteers received 3% sevoflurane for 8 h at 4-6 L/min. We measured inspired and expired concentrations of Compound A and urinary excretion of albumin, alpha-glutathione-S-transferase (GST), and glucose. The median urinary excretion of albumin, glucose, and alpha-GST for the first 3 days after anesthesia increased significantly from preanesthetic values in the 2-L/min group. Compound A doses < 240 ppm-h resulted in normal urinary excretion of albumin, glucose, and alpha-GST. Five of seven subjects who received doses > 240 ppm-h had abnormal excretion of albumin, and six of seven had abnormal alpha-GST urinary excretion (P < 0.05). Urinary excretion of albumin, alpha-GST, and glucose was normal by 14 days after exposure. We conclude that sevoflurane administration for 8 h at 2 L/min results in albuminuria and enzymuria when the dose of Compound A exceeds 240 ppm-h. That is, a Compound A concentration of 30 ppm breathed for > or = 8 h may produce transient renal injury.
  
  
  CONCLUSIONS
  We examined the dose-response relationship of sevoflurane/Compound A and urinary excretion of albumin, glucose, and alpha-GST. Sevoflurane exposure for 8 h at a 2-L/min inflow rate produces transient albuminuria and enzymuria in healthy volunteers when the dose of Compound A exceeds 240 ppm-h (30 ppm for 8 h).
authors.affiliation: Department of Anesthesiology, The Cooper Health System, University of Medicine and Dentistry of New Jersey, The Robert Wood Johnson Medical School at Camden, 08103, USA. mgoldberg@cooperhealth.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Goldberg
authors.forename: J
authors.initials: J
authors.lastname: Cantillo
authors.forename: I
authors.initials: I
authors.lastname: Gratz
authors.forename: E
authors.initials: E
authors.lastname: Deal
authors.forename: D
authors.initials: D
authors.lastname: Vekeman
authors.forename: R
authors.initials: R
authors.lastname: McDougall
authors.forename: M
authors.initials: M
authors.lastname: Afshar
authors.forename: A
authors.initials: A
authors.lastname: Zafeiridis
authors.forename: G
authors.initials: G
authors.lastname: Larijani
mesh_terms: D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000652:urine; D000764:Anesthesia, Closed-Circuit; D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis; D019540:Area Under Curve; D015415:Biomarkers / Q000032:analysis; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis; D005500:Follow-Up Studies; D005982:Glutathione Transferase / Q000652:urine; D006029:Glycosuria / Q000652:urine; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis; D000077149:Sevoflurane; D013147:Spirometry