Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 27 Clinical Biochemistry in Toxicology
Azotemia, elevation in blood urea nitrogen (BUN)
or creatinine, may occur as prerenal, renal, or postrenal.
Prerenal azotemia may result from dehydration or decreased
renal perfusion (e.g., cardiotoxins). Renal azotemia occurs
only after approximately 75% of the nephrons have lost
function.
Renal disease also results in elevation of serum creatinine.
The majority of serum creatinine originates from
the endogenous conversion of phosphocreatine in muscle,
which occurs at a relatively constant rate. Creatinine is not
reutilized. The creatine pool is modified by conditioning
and muscle disease. Creatinine also is distributed throughout
the compartment of total body water. It diffuses more
slowly than urea, however, and is not reabsorbed within
the tubules after leaving as glomerular filtrate. Creatinine
concentration is not affected significantly by diet, protein
catabolism, or urinary flow. Reduced renal perfusion
affects BUN and creatinine similarly ( Finco, 1997 ).
Elevations of BUN and creatinine are not proportional in
renal disease of ruminants because of reutilization of urea
by the rumen. Ingestion of the plant Nolletia gariepina has
been reported to cause renal failure in ruminants with a
measurable increase in urinary GGT along with azotemia
( Meintjes et al. , 2005 ) .
Hyperkalemia may occur in renal failure with oliguria
or anuria and acidosis. Hypercalcemia is common in
equines as a result of decreased renal clearance of calcium.
Hypocalcemia is more common in dogs, cats, and cattle
with chronic renal disease. Cattle also tend to have hypokalemia,
hyponatremia, and hypochloridemia with renal disease.
Mild to moderate increases of amylase and lipase may
also be seen in dogs with renal disease as these enzymes are
inactivated in the kidney ( Stockham and Scott, 2002 ).
Proteinuria in the absence of occult blood and cellular
sediment suggests renal disease. Glomerular lesions typically
result in high protein levels in which albumin is the
major constituent. Acute tubular damage observed with
many nephrotoxins generally results in lower protein levels
containing higher levels of smaller globulins and some albumin
( Stockham and Scott, 2002 ). Analysis of enzymes in
the urine can potentially determine the primary site of renal
damage because of the characteristic localization of enzymes
within the nephron. Increases in the brush border enzymes,
GGT and ALP, in the urine have been associated with renal
proximal tubular damage in dogs, whereas increases in
N-acetyl-beta-D-glucosaminidase have been observed in the
early stage of renal papillary necrosis. However, evaluation
of several enzymes at multiple time points is needed to compensate
for normal enzyme variation and to identify potential
anatomic site selectivity of the toxin ( Clemo, 1998 ).
Hypoproteinemia secondary to chronic urinary loss
(Kaneko, 1997a) promotes tissue edema and effusions that
may mimic cardiotoxicity and hepatotoxicity, as discussed
previously.
Bilirubin is considered to be mildly nephrotoxic.
Bilirubinuria may occur because of “ regurgitation ” of
conjugated bilirubin resulting from cholestatic hepatotoxins.
Myoglobin is also nephrotoxic. Myoglobinuria may
occur with toxic necrosis of skeletal and cardiac muscle.
Hemoglobin appears to be nephrotoxic in the presence of
concurrent dehydration or hypovolemia. Hemoglobinuria
may occur with hemolytic toxins.
Dehydration exacerbates the nephrotoxicity of many
agents, especially antibiotics in all species and nonsteroidal
anti-inflammatory drugs (phenylbutazone) in the horse.
Nephrotoxic antibiotics include the aminoglycosides (amikacin,
gentamicin, kanamycin, neomycin, streptomycin,
and tobramycin), amphotericin B, cephalosporins, polymixins,
sulfonamides, and tetracyclines ( Maxie, 1993 ).
Elevation of GGT in urine is a sensitive indicator of aminoglycoside
toxicity ( Gossett et al. , 1987 ).
Hypercalcemia and hyperphosphatemia may result in
nephrocalcinosis following iatrogenic hypervitaminosis
D or ingestion of cholecalciferol rodenticide ( Fooshee
and Forrester, 1990 ) by any species. Ingestion of the toxic
plants containing vitamin D-like analogues including
Cestrum diurnum, Dactylis glomerata , some Solanum spp.,
and Trisetum flavescens by herbivores also may produce
hypercalcemia with calcification of soft tissues including
the kidney.
Nephrotoxic metals include arsenic, bismuth, cadmium,
lead, mercury, and thallium ( Maxie, 1993 ).
Plants containing toxic concentrations of soluble oxalates
include the species Amaranthus retroflexus (pigweed),
Halogeton glomeratus, Oxalis spp., Rheum rhaponticum
(rhubarb), and Sarcobatus vermiculatus (greasewood).
Intoxication with ethylene glycol from antifreeze is one
of the more common accidental or malicious poisonings
encountered in dogs and cats. Birefringent hippurate
and oxalate crystals may be observed in urine sediments
(Kramer et al. , 1984 ). An increased anion gap and decreased
blood bicarbonate can be observed in animals with ethylene
glycol intoxication ( Dalefield, 2003 ). Blood calcium
is lowered in animals intoxicated with oxalate containing
plants that also have low calcium content. Blood calcium
is also decreased in animals with ethylene glycol toxicosis
( Stockham and Scott, 2002 ).
Nephrotoxic pyrrolizidine alkaloids include the plant
species listed under hepatotoxicity.
Trees of the genus Quercus (oaks) and Terminalia oblongata
(yellow-wood tree) contain tannins that induce acute
tubular necrosis when leaves, buds, or acorns are ingested.
Amaranthus retroflexus (pigweed), via an unidentified
toxic principle, also induces similar renal disease in cattle
( Casteel et al. , 1994 ) and pigs ( Osweiler et al. , 1969 ) in
the absence of oxalate nephrosis. At postmortem examination,
there were consistent elevations of urea and creatinine
concentrations in ocular fluid and serum.