Page 302 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Renal Toxicity Chapter | 16 269

VetBooks.ir for renal tubular necrosis (Harris et al., 1966). Clinical signs antifreeze, and dogs and cats are the most commonly
affected species, although all mammals are susceptible to
begin 2 days to a week or longer after animals have been
toxicosis. Ethylene glycol intoxication has three distinct
consuming large amounts of oak. Affected cattle initially
develop anorexia, depression, rumen stasis and constipation stages: (1) initial CNS depression and derangement due to
which are followed by diarrhea (1/ 2 blood), dehydration, an alcohol-like effect on the brain, (2) profound metabolic
colic, polyuria and subcutaneous edema of ventral areas acidosis with significant cardiorespiratory effects due to
such as neck, brisket, abdomen and perineum (Panciera, formation of acidic metabolites of ethylene glycol and (3)
1978). Clinical pathologic evaluation of serum reveals met- acute renal failure due to renal tubular injury (Thrall
abolic acidosis, elevations in BUN and serum creatinine, et al., 2006). Renal tubular injury is due to direct action
and electrolyte abnormalities (e.g., hyperkalemia). Cattle of the nephrotoxic metabolites glycoaldehyde and glyoxy-
with severe renal injury become weak and die, while less late on the renal tubules as well as mechanical injury and
severely affected animals may survive, although many will obstruction by calcium oxalate crystals (Thrall et al.,
become chronically debilitated due to persistent renal insuf- 2006; Maxie and Newman, 2007). Calcium oxalate crys-
ficiency (Burrows and Tyrl, 2001). The disease progression talluria is considered by some to be a hallmark of ethyl-
is similar in other species, though sheep and goats do not ene glycol, but crystalluria is present in less than half of
develop appreciable edema and horses tend to have more all intoxications. Therefore, the absence of oxalate crys-
severe diarrhea (1/ 2 blood), colic and tenesmus. Gross tals does not eliminate ethylene glycol as a potential toxi-
findings include fluid accumulations within body cavities, cant. Renal changes associated with ethylene glycol
subcutaneous edema, mesenteric edema and retroperitoneal intoxication include pale, swollen kidneys which may be
edema (especially perirenal). Kidneys are swollen, pale and gritty when cut. Microscopically, proximal tubular degen-
may have petechiae within the cortex; chronic cases may eration and necrosis is associated with the deposition of
have shrunken, irregular and fibrotic kidneys. Extra-renal birefringent, light yellow crystals arranged in sheaves,
lesions include edema, congestion, erosions and ulcerations rosettes or prisms (Maxie and Newman, 2007). Oxalate
of the alimentary tract mucosa and some cases may have crystals may also be found within tubular lumens, within
hepatocellular degeneration. renal tubular epithelial cells, and within the interstitium
(Fig. 16.2). Animals surviving more than a few days may
Vitis spp. show areas of tubular regeneration and/or interstitial
fibrosis. Extra-renal lesions may include deposition of
Ingestion of members of Vitis spp., including grapes, rai-
oxalate crystals within small vessels of the brain, heart,
sins and Zante currants, has been associated with acute
liver and intestinal mucosa.
renal failure in dogs (Morrow et al., 2005) and, anec-
dotally, cats and ferrets (ASPCA Animal Poison Control
Center, unpublished data). The toxic principle is unknown, Melamine:Cyanuric Acid
but attempts to identify known nephrotoxins such as myco-
In North America in 2007, the discovery of renal injury in
toxins, pesticides, vitamin D 3 and heavy metals have been
dogs and cats ingesting commercial pet foods led to the
unsuccessful. Affected dogs generally demonstrate vomit-
recall of over 60 million cans and pouches of “cuts and
ing and/or diarrhea within 12 h of ingestion of grapes or
gravy”-style pet food contaminated with melamine and
raisins, accompanied by anorexia, lethargy and abdominal
cyanuric acid. The contamination was found to have orig-
discomfort in some cases (Morrow et al., 2005). Severely
inated in wheat gluten from China, where the melamine
affected dogs rapidly progress to anuria, and death or
had been added to artificially inflate the apparent protein
euthanasia occurs within 23 289 h. Histopathological
level of the product. Cyanuric acid is a hydrolysis product
changes in the kidney include renal tubular degeneration
of melamine that may also have either been intentionally
and necrosis, primarily in the proximal tubules. Extensive
added or coincidentally present as a melamine by-product
sloughing of proximal tubule epithelium results in exten-
(Puschner et al., 2007). Subsequent to the pet food recall
sive necrotic debris within tubular lumens. Extra-renal
of 2007, the contamination of various food sources by
lesions consist of centrilobular hepatic degeneration or
melamine has been identified in several countries around
necrosis, myocardial necrosis, soft tissue mineralization
the world including Italy, China, Spain, Korea, Taiwan,
and fibrinous arteritis in colon, myocardium and aorta.
and other Asian countries (Brown et al., 2007; Gonzalez
et al., 2009; Yhee et al., 2009; Brown and Brown, 2010;
Miscellaneous Cocch et al., 2010). Separately, melamine and cyanuric
acid are of low toxicity, but in combination these com-
Ethylene Glycol pounds precipitate in acidic environments to form mela-
The most common cause of ethylene glycol toxicosis in mine cyanurate crystals (MCA) (Puschner et al., 2007). In
domestic animals is by consumption of automotive animals ingesting feed containing melamine and cyanuric