CE Article #4

Causes of Acute Renal Failure

Jennifer E. Stokes, DVM, DACVIM (Internal Medicine)a
Joseph W. Bartges, DVM, PhD, DACVIM (Internal Medicine), DACVN
University of Tennessee

ABSTRACT: Acute renal failure (ARF) is devastating in dogs and cats, with a mortality rate of
over 50%. Causes include prerenal, intrinsic renal, and postrenal conditions. Infectious disease
(leptospirosis, bacterial pyelonephritis, borreliosis) and toxicity (medications, plants, antifreeze) are
the most common causes of ARF in dogs and cats. Ureteral obstruction in cats is being recognized
more frequently as a postrenal cause of ARF.

A
cute renal failure (ARF) is due to
rapid hemodynamic, filtration, tubu-
lointerstitial, or excretory injury to
the kidneys, the outflow tract, or both. The
abrupt decrease in glomerular filtration rate
(GFR) results in accumulation of uremic tox-
ins and metabolic wastes, metabolic dysfunc-
tion, and dysregulation of fluid, electrolyte,
and acid–base balance.1 The kidneys are par-
ticularly susceptible to ischemic and toxic
damage because they receive 20% of cardiac
output. Certain medications are concentrated
in the kidneys secondary to tubular secretion
or reabsorption, which can predispose pa-
tients to renal injury. ARF can develop be-
cause of prerenal, intrinsic renal, or postrenal
causes.
Prerenal disease develops when the GFR
declines because of decreased renal blood flow
or increased renal vascular resistance. When
the mean arterial pressure is less than 70 to 80
mm Hg, renal perfusion is compromised. 1,2
Prerenal azotemia is a func-
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nal disease can coincide with
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prolonged prerenal azotemia can progress to
structural damage and intrinsic, irreversible
renal failure. 1 Many causes of prerenal azo-
temia are avoidable and/or easily treated
before subjecting patients to therapies that
may predispose them to ARF. Dehydrated
patients should be rehydrated before general
anesthesia or administration of potentially
nephrotoxic substances. In humans, volume
depletion leads to a tenfold increased risk
of developing ARF. Hypotension during
anesthesia and surgery can be avoided by
administering intravenous fluids and closely
monitoring blood pressure during medical
procedures.
Intrinsic causes of ARF result from renal
parenchymal damage due to ischemic, glomeru-
lar, or tubular disease. In dogs and cats, toxic,
infectious, and ischemic causes occur most
commonly.
Postrenal causes are due to obstruction or
rupture of the urinary tract. Obstruction may
occur from uroliths, neoplasia, trauma, inflam-
mation, fibrosis, blood or mucus, and congeni-
tal or acquired ureteral stenosis. If postrenal
ARF is recognized and treated early, most
cases are reversible. Postrenal disease lasting
longer than 7 days can cause renal parenchymal
damage and ARF.1

May 2006 387 COMPENDIUM

388 CE Causes of Acute Renal Failure

Potentially Nephrotoxic Medications Risk Factors for Acute Renal Failure

Antimicrobials • Preexisting renal disease
• Aminoglycosides • Amphotericin B • Decreased cardiac output
• Carbapenems • Cephalosporins • Dehydration
• Fluoroquinolones • Penicillins • Hypomagnesemia
• Rifampin • Sulfonamides • Advanced age
• Tetracyclines • Vancomycin • Hypocalcemia
Cancer chemotherapy
• Hypotension
• Bisphosphonates • Carboplatin • Hypokalemia
• Fever
• Cisplatin • Doxorubicin
• Hyponatremia
• Methotrexate
• Sepsis
Immunosuppressants • Acidosis
• Azathioprine • Cyclosporine • Hepatic insufficiency
Other medications • Concurrent use of potential nephrotoxins
• Allopurinol • Angiotensin-converting • Trauma
• Apomorphine enzyme inhibitors • Pancreatitis
• Dextran-40 • Cimetidine • Diabetes mellitus
• NSAIDs • Mannitol • Systemic hypertension
• Penicillamine • Streptokinase • Hypoalbuminemia
• Anesthesia and surgery
• Hypoadrenocorticism
• Vasculitis
MEDICATIONS
• Trauma
Medications associated with the induction of ARF are • Disseminated intravascular coagulation
listed in the box above. • Heatstroke
• Hyperviscosity syndrome (multiple myeloma,
Antimicrobials polycythemia)
Many antibiotics are potentially nephrotoxic to dogs
and cats. The nephrotoxic potential of these drugs
increases in animals with risk factors for ARF, including from the gastrointestinal (GI) tract. The dose adminis-
dehydration, hypotension, general anesthesia and surgery, tered in the four cats ranged from 70 to 208 mg/kg PO
and certain metabolic conditions. Additional risk factors q12h for fewer than 5 days; previous studies showed no
are listed in the box to the right. Prophylactic nafcillin toxicity at doses of 125 to 165 mg/kg PO q12h for 5
administration to prevent perioperative infection was days.5 All cats developed lethargy, vomiting, anorexia,
associated with postoperative ARF in seven dogs with no dehydration, and azotemia within 4 days after therapy
history of preexisting renal disease.3 was initiated. Azotemia improved or resolved within 6
Aminoglycosides are among the most nephrotoxic to 11 months in all cats. The cats may have been at a
antimicrobials, and their systemic use in animals has higher risk of developing renal toxicosis partly because
been associated with ARF for decades. Few cases of of increased systemic absorption of paromomycin from
aminoglycoside-induced ARF have been reported since diseased bowel.5
the 1980s, although there are two recent case reports
involving cats.4,5 One cat developed fatal ARF within 4 NSAIDs
days of topical administration of gentamicin to a soft Nephrotoxicity due to administration of NSAIDs,
tissue wound during lavage.4 A total dose of 232 mg/kg including selective cyclooxygenase (COX) inhibitors, is
was applied. The serum gentamicin level was greater most common in patients with concurrent renal disease,
than five times therapeutic concentrations.4 Four cats patients with conditions predisposing them to renal
administered paromomycin for treatment of large bowel damage, or those that have consumed greater-than-
diarrhea due to enteric trichomoniasis or cr yp- therapeutic doses.6,7 NSAIDs can decrease renal perfu-
tosporidiosis developed ARF.5 Paromomycin is an orally sion because prostaglandins (PGs) E2 and I2 mediate
administered aminoglycoside that is poorly absorbed afferent arteriolar dilation in response to decreased renal

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blood flow and PGI2 stimulates renin release. Most
studies7,8 in veterinary medicine have been conducted on
healthy patients undergoing elective procedures.
Carprofen did not decrease the GFR (based on renal
scintigraphy) or cause histopathologic changes in the
kidneys when administered to healthy dogs. Ketoprofen
has been associated with transient azotemia in healthy
dogs undergoing ovariohysterectomy.7
All NSAIDs represent a risk for renal function, although
not equally.7 Selective COX-2 inhibitors are reportedly
safer than nonselective NSAIDs in humans and cause
fewer GI and renal side effects. Both types of NSAIDs are
potentially toxic in dogs and cats, particularly because of
species differences in the expression and function of COX
isoforms. There are two isoforms of COX: COX-1 is
expressed constitutively and is involved in the production
of PGs needed for normal physiologic functions in several
organs, including the kidneys.9 COX-2 expression is
inducible by bacterial endotoxins, cytokines, and growth
factors but is also expressed constitutively in the kidneys in
the absence of inflammatory stimulation.7,9,10 COX-2
expression is greatly increased in dogs that are volume or
sodium depleted; therefore, administration of NSAIDs
that preferentially inhibit COX-2 may cause renal damage,
particularly in dehydrated patients.6
Renal disease in dogs has been associated with admin-
istration of aspirin, carprofen, flunixin meglumine,
naproxen, and phenylbutazone; however, ibuprofen is
the most common generic drug generating calls to the
National Animal Poison Control Center regarding dogs
and cats. 5,6,10 Appropriate intervention in cases of
ibuprofen-induced disease was more effective in manag-
ing GI disease than in preventing renal disease.11 ARF
generally occurred 36 hours or more after exposure,
whereas GI signs occurred within a few hours.11 In a
research setting,11,12 an ibuprofen dose of 300 mg/kg was
required to induce ARF in dogs, whereas clinical disease
has occurred with consumption of 200 mg/kg or less.
Cats are susceptible to ibuprofen doses approximately
one-half of those reported as toxic in dogs.11
NSAID use should be avoided in patients at high risk
of developing renal disease, including dehydrated
patients and those with cardiac or renal disease. Patients
undergoing general anesthesia and perioperative NSAID
administration should be well hydrated before anesthesia
and should receive fluid support to maintain normal
blood pressure. Most dogs that develop NSAID-induced
ARF have a favorable prognosis and generally respond
well after appropriate treatment for 5 to 10 days.6
May 2006
Causes of Acute Renal Failure CE 389
TOXICANTS
Ethylene Glycol
Ethylene glycol is a common cause of fatal poisoning
and ARF among dogs in the United States, with an
estimated 10,000 to 45,000 cases occurring annually.2,13
Because antifreeze is a widely available source of ethy-
lene glycol, cases most often occur during seasons in
which antifreeze is used. Ethylene glycol is also present
in industrial solvents, rust removers, color film process-
ing fluids, and heat-exchange fluids.
Ethylene glycol is absorbed quickly from the GI tract.
Blood concentration peaks within 1 to 4 hours after
ingestion, and almost all of the toxin is metabolized or
excreted within 18 to 24 hours after ingestion.13 Ethy-
lene glycol initially crosses the blood–brain barrier,
where it exerts narcotic or euphoric effects similar to
those of ethanol. The second clinical stage occurs when
ethylene glycol is metabolized to acidic intermediates,
including glycolic, glyoxylic, and oxalic acid, which
cause severe metabolic acidosis; this occurs within 3 to 4
hours after ingestion.13 Oxalate binds to plasma calcium,
forming calcium oxalate crystals in the renal tubules
(Figures 1 and 2). Signs of cardiopulmonary disease may
also develop.14
Two proposed mechanisms for renal tubular damage
include formation of calcium oxalate crystals in blood
vessels and renal tubules and direct nephrotoxic effects
of the metabolites of ethylene glycol. Animals that
develop ARF frequently show signs of severe depres-
sion, become comatose, and die.13 Lethal doses of 95%
ethylene glycol in cats and dogs are 1.4 to 4 ml/kg and 4
to 6.6 ml/kg, respectively.2,13,14 Antifreeze-induced ARF
might become less frequent with the use of brands that
contain propylene glycol, which is less toxic, or a bitter
aversive agent (denatonium benzoate).
Vitamin D
Vitamin D intoxication is well described in dogs and
cats. The most common source is ingestion of rodenti-
cides containing cholecalciferol (vitamin D3), which is
available in a variety of formulations and brand names.
In addition, toxicosis can occur from oversupplementa-
tion or feeding diets containing excessive vitamin D.
The major pathophysiologic effect is hypercalcemia,
which can cause ARF. Acute renal tubular damage
occurs as a result of altered cell membrane permeability,
altered calcium pump activity, decreased cellular energy
production, and cellular necrosis.15 The toxic dose in
naturally exposed dogs is 1.5 to 8 mg/kg, and the
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390 CE Causes of Acute Renal Failure
Figure 1. Ultrasonogram of a kidney from a dog with
acute renal failure due to ethylene glycol intoxication.
Note the “halo sign” (black arrow) as well as renal cortical
hyperechogenicity possibly due to calcium oxalate crystal
precipitation (white arrow).
median lethal dose is 13 mg/kg in adult dogs.16,17 The
toxic dose is unknown in cats. In general, puppies are
more susceptible to vitamin D toxicosis than are adult
dogs, and cats are more sensitive than dogs.17
Vitamin D toxicosis can occur with ingestion of
human medications containing vitamin D as treatment
of hypophosphatemic disorders, hypoparathyroidism,
osteomalacia, osteoporosis, and renal failure. An addi-
tional vitamin D toxicant is calcipotriene, which is a
synthetic analogue of calcitriol. Calcipotriene is the
active ingredient in Dovonex (Bristol-Myers Squibb), a
topical medication used to treat psoriasis in humans.18
Ingestion of calcipotriene can cause severe hypercal-
cemia, ARF, soft tissue mineralization, and death in
dogs.18,19 Within 12 to 24 hours after ingestion, dogs
exhibit vomiting, depression, anorexia, polyuria, and
diarrhea.18,19 Hypercalcemia, hyperphosphatemia, and
hypercalcemic nephropathy can occur within 18 to 72
hours; the animal can die from calcification of cardiac
tissue weeks after ingestion and resolution of acute clin-
ical signs and/or laboratory abnormalities.18,19
PLANTS
Raisins and Grapes
Since 2001, acute GI and renal toxicity has been
reported several times in dogs after ingestion of raisins or
grapes. Most cases have occurred since 1999 in both the
United States and United Kingdom.20,21 Affected dogs
consumed organic or commercial grapes, both red and
white varieties, as well as crushed or fermented grapes
COMPENDIUM
Figure 2. Calcium oxalate crystalluria discovered via
microscopic examination of urine sediment obtained
from a dog with acute renal failure due to ethylene glycol
intoxication. The elongated crystals are the monohydrate form,
and the octahedral-shaped ones are the dihydrate form.
from wineries. Raisins were mostly commercial sun-dried
varieties of various brands.20 Estimated amounts of
ingested raisins or grapes ranged from 3 to 57 g/kg.20–23 A
specific toxicant has not been identified. Contamination
of grapes and raisins with insecticides, pesticides, heavy
metals, or mycotoxins has been proposed and investigated
but not proven. There are no known reports of raisin or
grape toxicity in other species.
Initially, clinical signs of vomiting and lethargy develop
within hours after ingestion. Anorexia, diarrhea, and
abdominal pain have also been reported. ARF can
develop within 24 to 72 hours after ingestion of raisins or
grapes. Dogs may become oliguric or anuric. Death in
dogs with ARF secondary to raisin or grape ingestion has
occurred in 50% to 75% of reported cases.20,21,23 All dogs
that recovered were managed aggressively, including the
use of peritoneal dialysis in some cases.23 Histopathologic
findings included acute proximal renal tubular degenera-
tion or necrosis, metastatic mineralization of numerous
tissues, frequent tubular casts, intact basement mem-
branes, and evidence of renal tubular epithelial regenera-
tion.22,24 In one report 22 of 10 dogs with ARF associated
with grapes or raisins, a golden-brown globular pigment
was observed in the renal tubular epithelial cells in six
cases; its significance is unknown.
Lilies
Ingestion of members of the genera Lilium (Easter
lily, tiger lily, stargazer lily, Asiatic hybrid lily) and
Hemerocallis (common daylily [Figure 3], early daylily)
May 2006

Figure 3. Daylilies (Hemerocallis sp).
has been associated with ARF in cats.25–28 Other plants
commonly referred to as lilies (e.g., calla lily, peace lily)
are not nephrotoxic. The toxic principle in Easter lilies
is present in aqueous extracts of both flowers and leaves,
although flowers are more toxic. Doses equivalent to
one flower or eight leaves induced clinical toxicosis in
cats exposed in a research setting.26 The toxic principle
and dose are unknown for other lily species.
Lily toxicosis initially causes vomiting and ptyalism
after plant ingestion.25,26 Neurologic signs (e.g., ataxia,
depression, tremors and seizures, ARF) can also
develop.25 Renomegaly, renal pain, oliguria, and anuria
have been reported.25 In one report,28 cats diagnosed
with ARF developed severe azotemia 2 to 5 days after
ingestion (mean serum urea nitrogen: 215 mg/dl [nor-
mal: 15 to 34 mg/dl]; mean serum creatinine: 22.3
mg/dl [normal: 0.8 to 2.3 mg/dl]). Cylindruria, gluco-
suria, and proteinuria have been documented.26,27
Mortality rates of 50% to 100% have been reported in
cats developing ARF.25,27 There are no histopathologic
reports in daylily toxicosis cases, but histopathologic
changes in the kidneys of cats that have ingested Lilium
plants include acute renal tubular necrosis, interstitial
edema, polarized crystals in the collecting tubules, and
renal tubule epithelial cell regeneration.26,27 Although the
toxic agent can cause severe regional destruction of renal
tubular epithelial cells, basement membranes are usually
intact, thereby allowing possible tubular regeneration.
INFECTIOUS DISEASE
Leptospirosis
Leptospirosis is a worldwide zoonotic disease affecting
numerous species, including humans, dogs, and livestock.
It is caused by spirochete bacteria and has been reported
in dogs in the United States and Canada for more than
May 2006
Causes of Acute Renal Failure CE 391
Figure 4. Renomegaly characterized by generalized
edema, vascular stasis, and inflammation in a dog that
died from leptospirosis-induced acute renal failure.
100 years.29 There are more than 220 pathogenic lep-
tospiral serovars and many more that are avirulent.30
Pathogenic serovars are divided into three species31:
• Leptospira interrogans—serovars Canicola, Ictero-
haemorrhagiae, Bratislava, Hardjo, Pomona, Aus-
tralis, and Autumnalis
• Leptospira kirschneri—serovar Grippotyphosa
• Leptospira borgpetersenii—serovar Ballum
Serovars are maintained in the environment by one or
more reservoir hosts in which infection is typically
asymptomatic. Dogs are a reservoir host for the serovar
Canicola but also serve as secondary hosts for other
serovars that cause illness. Leptospiral infection can be
asymptomatic or cause ARF (Figure 4), hepatic disease,
coagulation disorders, or a combination of syndromes.
Historically, most cases of canine leptospirosis were
caused by serovars Canicola and Icterohaemorrhagiae,
but recent clinical reports31–35 have shown that the disease
is now most commonly associated with serovars Grippo-
typhosa, Pomona, Autumnalis, and Bratislava. The
change in the epidemiology of canine leptospirosis may
be due to urbanization leading to increased exposure of
dogs to wildlife and livestock reservoir hosts. In addition,
there has been a marked decrease in disease caused by
serovars Canicola and Icterohaemorrhagiae since wide-
spread vaccination of dogs beginning in the 1970s.
Studies36 have found that male dogs, dogs 4 years of
age or older, herding dogs, hounds, and working dogs are
at a significantly higher risk of developing this disease.
Despite these risk factors, leptospirosis is also diagnosed
in toy breeds and young dogs, and it is believed that
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392 CE Causes of Acute Renal Failure
Figure 5. Cut section of a kidney from a dog that died
from oliguric acute renal failure due to leptospirosis
serovar Bratislava.
German shepherds may be predisposed.32,33,37 There has
also been an association between increased rainfall and
increased numbers of cases of canine leptospirosis. 38
Most cases of clinical leptospirosis in dogs in the past
two decades have manifested as ARF with or without
hepatic involvement (Figure 5). Affected animals rarely
present with hepatic disease as the only clinical problem.
Once the organism penetrates mucous membranes or
abraded skin, it replicates in the vasculature and dissem-
inates to the kidneys, where it enters the interstitium.
Organisms can be seen within tubular cells and tubular
lumen within 2 weeks after infection.39 After colonizing
Many items, including medications, household plants,
and food products, are potentially nephrotoxic to dogs and cats.
renal tissue, the organism causes tubulointerstitial
nephritis with interstitial edema and cellular infiltrate,
which can lead to swelling and impaired renal perfusion.
Leptospiral organisms have several pathogenic factors
that are nephrotoxic. Leptospiral lipopolysaccharide
(LPS) and other outer-membrane components damage
cells. Leptospiral LPS is a potent macrophage activator
that stimulates secretion of interleukin-1 and interferon,
augmenting macrophage killing capacity.39 In vitro, the
LPS causes platelet aggregation, lysis, and degeneration
and stimulates release of tumor necrosis factor–α and
interleukin-10 by human peripheral blood mononuclear
cells.39 These cytokines may play a significant role in the
inflammatory response to leptospiral organisms.
COMPENDIUM
With early recognition, appropriate antibiotic therapy,
aggressive fluid therapy, and perhaps dialysis, many dogs
survive infection, although a mortality rate of 11% to 33%
has been reported.33,35,40 Serovar Pomona has been associ-
ated with a worse prognosis than have other serovars.31
Pyelonephritis
ARF due to pyelonephritis most commonly occurs sec-
ondary to ascending lower urinary tract infection caused
by naturally occurring bacterial cystitis or nosocomial
transmission via urinary catheterization. Hematogenous
spread of bacteria to the kidneys can also occur. Condi-
tions associated with hematogenous spread include bacte-
rial endocarditis, diskospondylitis, and pyometra, whereas
chronic bacterial cystitis, hyperadrenocorticism, and dia-
betes mellitus predispose patients to ascending infections.
Clinical signs of acute pyelonephritis may include fever,
lethargy, vomiting, anorexia, and renal pain. Laboratory
abnormalities may include leukocytosis with a left shift,
azotemia, pyuria, bacteriuria, and hematuria. Abdominal
radiography may demonstrate renomegaly (Figures 6 and
7), whereas ultrasonographic abnormalities may include
renomegaly, hyperechoic renal cortices, renal pelvic dila-
tion, and decreased corticomedullary junction. Animals
with chronic pyelonephritis may not have the described
clinical signs or abnormalities on diagnostic testing but
may still be in renal failure.
Escherichia coli is the most common organism isolated
in cases of canine bacterial pyelonephritis. Several
strains have uropathogenic factors that allow them to
colonize the urinary tract, including adhesins that
increase bacterial adherence to epithelial cells. Strains of
E. coli – causing pyelonephritis are more adhesive than
those causing bacterial cystitis.39 Additional virulence
factors associated with pyelonephritis-causing E. coli
include hemolysin, cytotoxic necrotizing factor, aero-
bactin, and secreted autotransporter toxin.39
Lyme Disease
Lyme disease is caused by the spirochete bacterium
Borrelia burgdorferi and is transmitted by ticks of the
genus Ixodes. Dogs with borreliosis are most frequently
asymptomatic, but clinical disease can manifest as lame-
May 2006

Figure 6. Lateral radiograph demonstrating bilateral
renomegaly in a cat with E. coli pyelonephritis.
ness, fever, lethargy, and anorexia. Cardiac and neurologic
signs are rare.41 Dogs typically improve within 48 hours
of administration of appropriate antimicrobial therapy.41
Although the incidence of Lyme disease is unknown,
the disease has been associated with severe protein-losing
glomerulopathy and ARF in dogs.41 From 1987 to 1992,
several dogs in Lyme-endemic areas were diagnosed with
rapidly progressing glomerulopathy.42 Labrador retrievers,
golden retrievers, and Shetland sheepdogs appear predis-
posed.41 Most affected dogs presented with sudden onset
of anorexia, vomiting, lethargy, and weight loss and devel-
oped ARF with proteinuria, peripheral edema, and body
cavity effusion. Clinical disease progressed rapidly, usually
leading to euthanasia or death within 1 to 2 weeks,
although three dogs lived for several months.41
Of the dogs tested, all had positive results for B.
burgdorferi via serology.42 Other dogs had spirochetes in
renal tissue, and one tested positive for B. burgdorferi via
urine culture; however, more sensitive molecular tech-
niques found little evidence of B. burgdorferi in banked
tissue from affected dogs.41,43 Further research needs to
be conducted to determine whether Lyme disease, vac-
cination for Lyme disease, or an unidentified organism
is associated with the severe renal lesions of the condi-
tion called canine Lyme nephritis.
ISCHEMIC CAUSES
Ischemic causes of ARF include hypovolemia, hypoten-
sion, and thromboembolic disease. Disseminated intravas-
cular coagulation due to pancreatitis, immune-mediated
disease, neoplasia, heatstroke, or other diseases can lead to
ARF (Figure 8). Injury occurs when renal blood flow is
May 2006
Causes of Acute Renal Failure CE 393
Figure 7. Ventrodorsal radiograph demonstrating
bilateral renomegaly in a cat with E. coli pyelonephritis.
reduced because of decreased blood pressure, micro-
thrombi, or renal vasoconstriction. Decreased perfusion
leads to accumulation of metabolic wastes, decreased
delivery of cellular nutrients, and hypoxia. Stores of ATP
are rapidly used, and when ATP deficiency occurs, the
ATPase pump is unable to maintain normal cellular trans-
port of sodium, potassium, and calcium. Increased intra-
cellular calcium levels cause further vasoconstriction and
cell membrane damage. Cell swelling occurs with accu-
mulation of intracellular sodium. Vasoconstriction and cell
swelling lead to vascular stasis and occlusion of the blood
supply to the renal cortex, causing further ischemic dam-
age. Decreased delivery of nutrients leads to cell mem-
brane damage and formation of oxygen-derived free
radicals, which also damage cell membranes.
MISCELLANEOUS CAUSES
Rarely reported causes of ARF in dogs include enven-
omation by poisonous snakes and bull ants.44,45 Snake
venom contains nephrotoxins that produce renal ische-
mia, alterations in renal hemodynamics, and coagulation
disorders, all of which can lead to ARF.45
Administration of an iodinated radiographic contrast
medium (e.g., sodium iopanoate, diatrizoate meglumine,
diatrizoate sodium) has rarely been reported as a cause of
ARF in dogs, although it is the third leading cause of
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394 CE Causes of Acute Renal Failure
Figure 8. Kidneys from a dog that died from disseminated intravascular coagulation associated with heatstroke. Notice
the pitting of the renal surface due to thromboembolization and subsequent ischemia.
ARF in hospitalized humans.46–48 The exact mechanism
for ARF associated with a radiographic contrast medium
is unknown, although nephrotoxicity is dose dependent
and more severe in dehydrated dogs.47 Renal damage
may occur because of direct renal tubular cell toxicity,
tubular obstruction, hypotension, and renal medullary
ischemia.47 Risk factors in humans include renal insuffi-
ciency, congestive heart failure, dehydration, and possibly
diabetes mellitus.48 A low osmolar contrast medium,
such as iohexol, iopamidol, or iopromide, is less nephro-
toxic.49 Intravenous saline infusion before administration
of intravenous contrast medium appears to decrease the
occurrence of ARF in humans. A common protocol to
prevent ARF in humans is intravenous 0.45% saline at a
rate of 1 to 1.5 ml/kg/hr for 6 to 12 hours before and 12
hours after contrast media administration.49
Miscellaneous causes of ARF are listed in the box on
page 395.
POSTRENAL CAUSES
Postrenal ARF due to obstruction or diversion of
urine results in retention of excretory products in the
body. Uroliths, mucous plugs, blood clots, or intra- or
extraluminal masses are the most common causes of
obstruction. If bilateral ureteral obstruction occurs, it is
usually due to transitional cell carcinoma at the bladder
trigone, although it can be due to other causes.
COMPENDIUM
Ureteral obstruction is being increasingly recognized as
a cause of ARF in cats. From 1993 to 2003,49 37% of 119
cats undergoing dialysis for management of ARF had
acute ureteral obstruction. All reported cats with ureteral
obstruction presented from 1999 to 2003 and represented
50% of all cases.49 Most cats presented after sequential
obstruction of both ureters due to calcium oxalate
ureteroliths (approximately 75% of the reported cases) or
organic material.49 Although most cats presented with
severe azotemia (serum creatinine: >7 mg/dl), many
appeared less ill than cats with similar degrees of azotemia
due to other causes.49 The physical examination findings
included asymmetric and/or painful kidney(s). Radio-
graphic abnormalities included renal asymmetry, bilateral
renomegaly, expansion of the retroperitoneal space, or
ureteroliths. 49 Ultrasonography diagnosed ureteral
obstruction in approximately 75% of cats, although it may
take up to 7 days after complete obstruction for ultrasono-
graphic changes to be detected.49 In 20% to 30% of cats,
no discrete mineralized material was identified with rou-
tine abdominal imaging. Antegrade pyelography using
ultrasonographic guidance to inject contrast medium into
the renal pelvis has been used to detect ureteral obstruc-
tions that were inapparent with routine radiography or
that involved multiple areas of the ureter.49
Approximately 25% of cats with ureteral obstruction
that were initially managed with hemodialysis had
May 2006

spontaneous resolution of the obstruction within 2 to 5
days. An additional 40% with mild uremia were success-
fully managed with routine medical treatment. In cases
in which spontaneous resolution did not occur or
hemodialysis was unavailable, surgical resolution was
necessary. In the perioperative period, approximately
20% of cats died as a result of surgical complications. In
cats surviving the perioperative period, 2-year survival
was greater (88%) than in cats managed nonsurgically
(66%).49 Renal transplantation may be an additional
treatment option in select cases.
Posturethral obstruction is another potential cause of
ARF. Uroliths, mass lesions, foreign bodies, or strictures
in the urethral orifice, whether originating from the
lower urinary tract or genital tract, can cause urinary
outflow obstruction and postrenal ARF.
PROGNOSIS
The mortality rate of ARF varies, depending on the
cause, extent of damage, concurrent diseases, and timing
and effectiveness of therapy. Mortality associated with all
causes of ARF in dogs ranges from 56% to 80%.40,50,51
Factors associated with increased mortality vary among
studies40,50,51 but include severity of azotemia (initial
serum creatinine: >10 mg/dl), hypocalcemia (total serum
calcium: <8.6 mg/dl), proteinuria, gender, age, oliguria or
anuria, anion gap, and phosphorus concentration. Dogs 7
years of age or older had an approximately ninefold risk
of death, whereas oliguric dogs were 20 times more likely
to die.51 The mortality rate also varies by cause: infectious
(30%), hemodynamic/metabolic (44%), and toxic (82%).52
Ethylene glycol–induced ARF carries a poor prognosis,
with 88% to 100% of dogs dying or being euthanized.40,52
Less information is available concerning the prognosis
in cats with ARF. In one retrospective study53 of 25 cases,
56% of cats died or were euthanized. Mortality was higher
for the 72% of cats that presented with anuria or oliguria;
all nonoliguric or polyuric cats survived.53 All cats that
were oliguric and in ARF due to nephrotoxic causes and
those that were anuric died. A second retrospective study54
assessing 119 cats treated with hemodialysis for ARF
showed an overall mortality rate of 48%. Mortality was
lowest (25%) in cats that had obstructive ARF.54
CONCLUSION
Despite the availability of aggressive medical therapy
and dialysis for ARF, the mortality rate remains high. It
is important for veterinarians to be aware of new and
reemerging causes of ARF in cats and dogs. Recognizing
May 2006
Causes of Acute Renal Failure CE 395
Miscellaneous Causes
of Acute Renal Failure
• Administration of contrast medium
• Heavy metals (mercury, gold, nickel, thallium, lead)
• Carbon tetrachloride
• Snake and bee venom
• Hemoglobin, myoglobin
• Amanita phalloides (mushroom)
• Hyperthermia (heatstroke)
causes of ARF as well as predisposing factors, many of
which are preventable and/or hospital acquired, can help
decrease the incidence of and mortality due to ARF.
REFERENCES
1. Cowgill LD, Francey T: Acute uremia, in Ettinger SJ, Feldman EC (eds):
Textbook of Veterinary Internal Medicine. Philadelphia, Elsevier Saunders,
2005, pp 1731–1751.
2. Tefend M: Acute renal failure: Diagnosis and treatment. Proc ACVIM
Forum:40–42, 2005.
3. Pascoe PJ, Ilkiw JE, Kass PH, et al: Case-control study of the association
between intraoperative administration of nafcillin and acute postoperative
development of azotemia. JAVMA 208(7):1043–1047, 1996.
4. Mealey KL, Boothe DM: Nephrotoxicosis associated with topical adminis-
tration of gentamicin in a cat. JAVMA 204(12):1919–1921, 1994.
5. Gookin JL, Riviere JE, Gilger BC, et al: Acute renal failure in four cats
treated with paromomycin. JAVMA 215(12):1821–1823, 1999.
6. Forrester SD, Troy GC: Renal effects of nonsteroidal antiinflammatory
drugs. Compend Contin Educ Pract Vet 21(10):910–919, 1999.
7. Lobetti RG, Joubert KE: Effect of administration of nonsteroidal anti-
inflammatory drugs before surgery on renal function in clinically normal
dogs. Am J Vet Res 61(12):1501–1507, 2000.
8. Trepanier LA: Drug interactions and differential toxicity of NSAIDs. Proc
ACVIM Forum:535–537, 2004.
9. Khan KN, Venturini CM, Bunch RT, et al: Interspecies differences in renal
localization of cyclooxygenase isoforms: Implications in nonsteroidal antiin-
flammatory drug-related nephrotoxicity. Toxicol Pathol 26(5):612–620, 1998.
10. Forsyth SF, Guilford WG, Pfeiffer DU: Effect of NSAID administration on
creatinine clearance in healthy dogs undergoing anaesthesia and surgery. J
Small Anim Pract 41(12):547–550, 2000.
11. Poortinga EW, Hungerford L: A case-control study of acute ibuprofen toxic-
ity in dogs. Prev Vet Med 35(2):115–124, 1998.
12. Villar D, Buck WB, Gonzalez JM: Ibuprofen, aspirin and acetaminophen tox-
icosis and treatment in dogs and cats. Vet Hum Toxicol 40(3):156–162, 1998.
13. Oehme FW: Antifreeze poisoning: Diagnosis, treatment options. Proc
ACVIM Forum:50–51, 2000.
14. Dorman DC, Dye JA: Chemical toxicities, in Ettinger SJ, Feldman EC (eds):
Textbook of Veterinary Internal Medicine. Philadelphia, Elsevier Saunders,
2005, pp 257–258.
15. Morrow CM: Cholecalciferol poisoning. Vet Med 905–911, 2001.
16. Murphy MJ: Rodenticides. Vet Clin North Am Small Anim Pract 32(2):
469–484, 2002.
17. Rumbeiha WK, Fitzgerald SD, Kruger JM, et al: Use of pamidronate di-
sodium to reduce cholecalciferol-induced toxicosis in dogs. Am J Vet Res
61(1):9–13, 2000.
18. Welch SL: Oral toxicity of topical preparations. Vet Clin North Am Small
Anim Pract 32(2):443–453, 2002.
19. Fan TM, Simpson KW, Trasti S, et al: Calcipotriol toxicity in a dog. J Small
Anim Pract 39(12):581–586, 1998.
20. Gwaltney-Brant S, Holding JK, Donaldson CW, et al: Renal failure associated
with ingestion of grapes or raisins in dogs. JAVMA 218(10):1555–1556, 2001.
COMPENDIUM
396 CE Causes of Acute Renal Failure

21. Campbell A, Bates N: Raisin poisoning in dogs. Vet Rec 152(12):376, 2003. in dogs: 29 cases (1983–1992). JAVMA 208(4):537–541, 1996.
22. Morrow CM, Valli VE, Volmer PA, et al: Canine renal pathology associated 52. Francey T, Cowgill LE: Use of hemodialysis for the management of acute renal
with grape or raisin ingestion: 10 cases. J Vet Diagn Invest 17(3):223–231, failure in the dog: 124 cases (1990–2001). Proc ACVIM Forum:786, 2002.
2005. 53. Worwag S, Langston CE: Retrospective, acute renal failure in cats: 25 cases
23. Mazzaferro EM, Eubig PA, Hackett TB, et al: Acute renal failure associated (1997–2002). Proc ACVIM Forum:827, 2004.
with raisin or grape ingestion in 4 dogs. J Vet Emerg Crit Care 14(3):203–212, 54. Pantaleo V, Francey T, Fischer JR, et al: Applications of hemodialysis for the
2004. management of acute uremia in cats: 119 cases (1993–2003). Proc ACVIM
24. Penny D, Henderson SM, Brown PJ: Raisin poisoning in a dog. Vet Rec Forum:829, 2004.
152(10):308, 2003.
25. Hadley RM, Richardson JA, Gwaltney-Brant SM: A retrospective study of
ARTICLE #4 CE TEST
daylily toxicosis in cats. Vet Human Toxicol 45(1):38–39, 2003.
26. Rumbeiha WK, Francis JA, Fitzgerald SD, et al: A comprehensive study of
Easter lily poisoning in cats. J Vet Diagn Invest 16(6):527–541, 2004.
This article qualifies for 2 contact hours of continuing CE
27. Brady MA, Janovitz EB: Nephrotoxicosis in a cat following ingestion of Asi-
education credit from the Auburn University College of
atic hybrid lily (Lilium sp). J Vet Diagn Invest 12(6):566–568, 2000. Veterinary Medicine. Paid subscribers may purchase
28. Langston CE: Acute renal failure caused by lily ingestion in six cats. JAVMA individual CE tests or sign up for our annual CE
220(1):49–52, 2002.
program. Those who wish to apply this credit to fulfill state
29. Ward MP: Clustering of reported cases of leptospirosis among dogs in the
United States and Canada. Prev Vet Med 56(3):215–226, 2002. relicensure requirements should consult their respective
30. Kalin M, Devaux C, DiFruscia R, et al: Three cases of canine leptospirosis in state authorities regarding the applicability of this program.
Quebec. Can Vet J 40(3):187–191, 1999. To participate, fill out the test form inserted at the end of
31. Goldstein RE: Canine leptospirosis. Proc ACVIM Forum:573–575, 2004. this issue or take CE tests online and get real-time scores at
32. Harkin KR, Gartrell CL: Canine leptospirosis in New Jersey and Michigan:
17 cases (1990–1995). JAAHA 32(6):495–501, 1996. CompendiumVet.com.Test answers are available online
33. Brown CA, Roberts AW, Miller MA, et al: Leptospira interrogans serovar free to paid subscribers as well.
grippotyphosa infection in dogs. JAVMA 209(7):1265–1267, 1996.
34. Birnbaum N, Barr SC, Center SA, et al: Naturally acquired leptospirosis in 1. Which is the most common cause of ARF in dogs
36 dogs: Serological and clinicopathological features. J Small Anim Pract
39(5):231–236, 1998. and cats?
35. Adin CA, Cowgill LD: Treatment and outcome of dogs with leptospirosis: a. ischemia c. infectious disease
36 cases (1990–1998). JAVMA 216(3):371–375, 2000. b. nephrotoxicity d. urinary tract obstruction
36. Ward MP, Glickman LT, Guptill LE: Prevalence of and risk factors for lep-
tospirosis among dogs in the United States and Canada: 677 cases
(1970–1998). JAVMA 220(1):53–58, 2002. 2. Which is an approximate overall mortality rate
37. Hrinivich K, Prescott JF: Leptospirosis in 2 unrelated dogs. Can Vet J for ARF in dogs?
38(8):509–510, 1997.
38. Ward MP: Seasonality of canine leptospirosis in the United States and a. 2% c. 60%
Canada and its association with rainfall. Prev Vet Med 56(3):203–213, 2002. b. 15% d. 95%
39. Sykes JE: Mechanisms of renal injury by infectious agents. Proc ACVIM
Forum:201–203, 2003.
40. Forrester SD, McMillan NS, Ward DL: Retrospective evaluation of acute 3. Which medication(s) is potentially nephrotoxic?
renal failure in dogs. Proc ACVIM Forum:788, 2002. a. penicillin c. doxorubicin
41. Littman MP: Canine borreliosis. Vet Clin North Am Small Anim Pract b. ibuprofen d. all of the above
33(4):827–862, 2003.
42. Dambach DM, Smith CA, Lewis RM, et al: Morphologic, immunohisto-
chemical, and ultrastructural characterization of a distinctive renal lesion in 4. Which is a reemerging disease that has been
dogs putatively associated with Borrelia burgdorferi infection: 49 cases confirmed as a cause of ARF in dogs and/or cats?
(1987–1992). Vet Pathol 4(2):85–96, 1997.
43. Shaines TA, Goldstein RE, Njaa BL, et al: The search for intact Borrelia a. FIV c. bartonellosis
burgdorferi bacteria in kidneys from dogs suspected of suffering from “Lyme b. borreliosis d. leptospirosis
nephritis.” Proc ACVIM Forum:925, 2005.
44. Puig J, Vilafranca M, Font A, et al: Acute intrinsic renal failure and blood
coagulation disorders after a snakebite in a dog. J Small Anim Pract 5. Which predispose(s) animals to ARF?
36(7):333–336, 1995. a. dehydration c. advanced age
45. Abraham LA, Hinkley CJ, Tatarczuch L, et al: Acute renal failure following
bull ant mass envenomation in two dogs. Aust Vet J 82(1–2):43–47, 2004.
b. aminoglycoside d. all of the above
46. Burgener FA, Fischer HW: Nephrotoxicity of sodium iopanoate in hydrated administration
and dehydrated dogs. Invest Radiol 3(3):247–254, 1978.
47. Ihle SL, Kostolich M: Acute renal failure associated with contrast medium
administration in a dog. JAVMA 199(7):899–901, 1991.
6. Ethylene glycol toxicosis
48. Cox CD, Tsikouris JP: Preventing contrast nephropathy: What is the best a. can cause neurologic or cardiopulmonary signs.
strategy? A review of the literature. J Clin Pharmacol 44(4):327–337, 2004. b. has a good prognosis (>80% survival) when patients
49. Cowgill LE: Ureteral obstruction: A new dilemma in feline nephrology. Proc are managed with hemodialysis.
ACVIM Forum:748–749, 2005.
c. is a rare cause of poisoning in dogs.
50. Vaden SL, Levine J, Breitschwerdt EB: A retrospective case-control of acute
renal failure in 99 dogs. J Vet Intern Med 11(2):58–64, 1997. d. leads to the development of severe metabolic alkalo-
51. Behrend EN, Grauer GF, Mani I, et al: Hospital-acquired acute renal failure sis.

COMPENDIUM May 2006

7. Which mechanism has been proven for raisin 9. Which NSAID is most commonly associated
toxicity in dogs? with accidental ingestion in dogs?
a. hypercalcemia c. heavy metal toxicity a. ibuprofen c. meloxicam
b. calcium oxalate formation d. none of the above b. carprofen d. aspirin
in renal tubules
8. Which source(s) of cholecalciferol has been asso- 10. Which organism is most commonly associated
ciated with ARF in dogs and/or cats? with pyelonephritis?
a. oversupplemented diets c. topical preparations a. Pseudomonas spp c. Bacteroides spp
b. rodenticides d. all of the above b. E . coli d. Staphylococcus spp

May 2006 COMPENDIUM