title: Pathology and proposed pathophysiology of diclofenac poisoning in free-living and experimentally exposed oriental white-backed vultures (Gyps bengalensis).
abstract: Oriental white-backed vultures (Gyps bengalensis; OWBVs) died of renal failure when they ingested diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), in tissues of domestic livestock. Acute necrosis of proximal convoluted tubules in these vultures was severe. Glomeruli, distal convoluted tubules, and collecting tubules were relatively spared in the vultures that had early lesions. In most vultures, however, lesions became extensive with large urate aggregates obscuring renal architecture. Inflammation was minimal. Extensive urate precipitation on the surface and within organ parenchyma (visceral gout) was consistently found in vultures with renal failure. Very little is known about the physiologic effect of NSAIDs in birds. Research in mammals has shown that diclofenac inhibits formation of prostaglandins. We propose that the mechanism by which diclofenac induces renal failure in the OWBV is through the inhibition of the modulating effect of prostaglandin on angiotensin II-mediated adrenergic stimulation. Renal portal valves open in response to adrenergic stimulation, redirecting portal blood to the caudal vena cava and bypassing the kidney. If diclofenac removes a modulating effect of prostaglandins on the renal portal valves, indiscriminant activation of these valves would redirect the primary nutrient blood supply away from the renal cortex. Resulting ischemic necrosis of the cortical proximal convoluted tubules would be consistent with our histologic findings in these OWBVs.
authors.affiliation: USGS National Wildlife Health Center, 6006 Schroeder Rd., Madison, Wisconsin 53711, USA. carol_meteyer@usgs,gov
authors.forename: Carol Uphoff
authors.initials: CU
authors.lastname: Meteyer
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Rideout
authors.forename: Martin
authors.initials: M
authors.lastname: Gilbert
authors.forename: H L
authors.initials: HL
authors.lastname: Shivaprasad
authors.forename: J Lindsay
authors.initials: JL
authors.lastname: Oaks
mesh_terms: D000818:Animals; D000835:Animals, Wild; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000506:poisoning*; D001715:Bird Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002423:Cause of Death; D004008:Diclofenac / Q000378:metabolism / Q000506:poisoning*; D004350:Drug Residues / Q000506:poisoning*; D046093:Falconiformes; D020387:Food Chain; D006073:Gout / Q000139:chemically induced / Q000473:pathology / Q000662:veterinary; D051437:Renal Insufficiency / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac