title: Renal dysfunction associated with the perioperative use of diclofenac.
abstract: Postoperative renal dysfunction in rats is induced by ketorolac dosed concurrently with gentamicin. Herein, we report the renal effects of diclofenac in four groups of rats: control (C = anesthesia, surgery); diclofenac (D = anesthesia, surgery, diclofenac 18 mg x kg(-1) x d(-1)); gentamicin (G = anesthesia, surgery, gentamicin 20 mg x kg(-1) x d(-1)); and diclofenac and gentamicin (DG = anesthesia, surgery, diclofenac, gentamicin). Renal function, after three treatment days, was assessed using histology, p-aminohippurate (PAH), and iothalamate (IOT) clearances, serum and urine electrolytes, osmolality, urea, and creatinine. Urine output was increased (from 5.2 to 12.5 mL/24 h), and urine osmolality was decreased (from 2121 to 883 mOsm/kg) in the DG group. PAH and IOT clearances were decreased in the G and DG groups (PAH by 18%, IOT by 22%; PAH by 38%, IOT by 43%, respectively); there were no changes in the C and D groups. Urea and creatinine clearances were decreased by 61% and 43%, respectively, in the DG group. Kidney sections showed the most severe pathologic changes in the DG group. Our data indicate that the perioperative combination of diclofenac and gentamicin was deleterious to renal function.
  
  
  CONCLUSIONS
  Diclofenac alone does not result in significant perioperative renal dysfunction, but the combination of gentamicin and diclofenac is deleterious to renal function. Considering this and previous findings, the evidence suggests that treatment with aminoglycosides may be a significant risk factor for inducing perioperative renal failure during treatment with nonsteroidal antiinflammatory drugs.
authors.affiliation: Department of Anaesthesia, University of Sydney at Royal North Shore Hospital, St Leonards, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.forename: M J
authors.initials: MJ
authors.lastname: Cousins
authors.forename: R P
authors.initials: RP
authors.lastname: Eckstein
authors.forename: V
authors.initials: V
authors.lastname: Jordan
authors.forename: I
authors.initials: I
authors.lastname: Power
authors.forename: L E
authors.initials: LE
authors.lastname: Mather
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D003287:Contrast Media; D003404:Creatinine / Q000097:blood / Q000652:urine; D004008:Diclofenac / Q000009:adverse effects*; D004338:Drug Combinations; D005500:Follow-Up Studies; D005839:Gentamicins / Q000009:adverse effects; D007483:Iothalamic Acid; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000097:blood / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D012964:Sodium / Q000097:blood / Q000652:urine; D014508:Urea / Q000097:blood / Q000652:urine; D014554:Urination / Q000187:drug effects; D014556:Urine; D010130:p-Aminohippuric Acid
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003287:Contrast Media; D004338:Drug Combinations; D005839:Gentamicins; D004008:Diclofenac; D007483:Iothalamic Acid; D014508:Urea; D012964:Sodium; D003404:Creatinine; D011188:Potassium; D010130:p-Aminohippuric Acid