J Wildl Dis: Pathology and proposed pathophysiology of diclofenac poisoning in free-living and experimentally exposed oriental white-backed vultures (Gyps bengalensis).
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.