
Featured case study: 9-year-old spayed female
cocker spaniel, Milly Submitted by
Mary Lindsay, DVM, Westfield Veterinary Group and Wellness Center, 562 Springfield Avenue, Westfield, New Jersey
Physical examination Other than age-related bilateral
nuclear sclerosis and mild bilateral chronic otitis, Milly was in good body condition with no
abnormal physical examination findings.
Differential diagnoses Diabetes mellitus, diabetes
insipidus (central or nephrogenic), chronic renal failure, glomerular disease, glomerulonephritis,
amyloidosis, hyperadrenocorticism, psychogenic polydipsia with medullary washout and
pyelonephritis were all considered as differentials for the PU/PD. Neurogenic (upper motor vs.
lower motor neuron) and nonneurogenic incontinence (hormone-responsive incontinence, urge
incontinence) were also considered as contributors to the urinary accidents as were transitional
cell carcinoma, vaginal or urethral mass and urinary tract infection.
Diagnostic plan A complete blood count (CBC), general
chemistry profile, complete urinalysis with urine culture and sensitivity were performed to screen
for metabolic, infectious and inflammatory disease and to potentially characterize primary and
secondary organ involvement.
Laboratory data
Erythron—The minimal elevation of MCHC supports the potential
of cell-free hemoglobin due to in vitro or in vivo hemolysis.
Leukon—All parameters are within reference-interval-limits;
however, the lymphocyte count at the extreme low end of the reference interval is highly suspect
for an underlying glucocorticoid influence (stress).
Thrombon—There is a minimal and insignificant thrombocytosis present.
Blood film review—No significant morphologic abnormalities
are noted in any cell line.
Clinical chemistry
Kidney panel—There was a increase in the BUN without an
increase in creatinine suggesting nonrenal causes, including gastrointestinal bleeding and/or
recent high-protein diet. Although there is no support for decreased glomerular filtration because
of the within-reference-interval creatinine, the potential for underlying renal disease should be
maintained in the differential because of the nonconcentrated urine specific gravity. Serial
laboratory profiling for renal disease (clinical chemistries and urinalyses) should be considered
for further evaluation. There was evidence of significant proteinuria, and since there was no
evidence of active inflammation or sediment changes explaining this proteinuria, renal proteinuria
was indicated. A urine protein:creatinine ratio (UPC) was determined to quantify the degree of
proteinuria and provide baseline values for trending over time during case management and reevaluation.
Electrolyte Profile—The finding of moderately increased
potassium and a mild decreased sodium:potassium ratio (23, reference interval > 27) warrants
investigating a series of possible causes. Differentials for decreased sodium:potassium ratio
include hypoadrenocorticism, chronic renal failure, intestinal parasitism and thrombocytosis with
potassium release from platelets. If Milly were an Akita or other Japanese canine breed, the
potential of hemolysis and release of intracellular potassium from erythrocytes would have been
considered, since these breeds have a relatively high intraerythrocyte potassium concentration
compared to others. Since there was no laboratory support for renal failure, there was no
significant thrombocytosis. Because Milly was not a breed of dog with high intraerythrocyte
potassium concentration, investigating hypoadrenocorticism was warranted even though there was
evidence of a glucocorticoid influence in the CBC. An adrenocorticotropic hormone (ACTH)
stimulation test was performed to screen for hyperadrenocorticism and rule out hypoadrenocorticism.
Additional diagnostics
Abdominal Ultrasound—The kidneys were found to have
abnormally increased echogenicity and there were multiple smoothly marginated anechoic cysts
present in the cortices of both kidneys. Renal corticomedullary definition was bilaterally
reduced. These changes were consistent with chronic immune-mediated or infectious renal disease.
The right and left adrenals were of normal size, shape and echogenicity.
Diagnostic summary An ACTH stimulation test, with pre-ACTH
and post-ACTH cortisol levels within-reference-interval limits, while ruling out
hypoadrenocorticism, does not rule out hyperadrenocorticism as approximately 40% of dogs with
hyperadrenocorticism will have within-reference-interval results.1
The finding of normal-appearing adrenals on the abdominal ultrasound in this patient makes
pituitary-dependent hyperadrenocorticism unlikely and rules out an adrenal tumor. Proteinuria may
be due to prerenal, renal and postrenal causes. Prerenal causes of proteinuria due to increased
glomerular permeability, including shock, heart disease, fever and strenuous exercise, have been
excluded as likely causes in this case because of the clinical presentation and physical
examination findings. Overflow proteinuria where high concentrations of low-molecular-weight
proteins in the peripheral blood are filtered and not reabsorbed, including hemoglobin, myoglobin
and Bence Jones proteins, has been considered unlikely, again because of clinical presentation and
laboratory data evaluation. It should be remembered that Bence Jones proteins commonly do not
react with dry-reagent urinalysis strips, which results in a negative protein result or only
minimal positive protein even in the face of marked proteinuria. Postrenal causes of proteinuria,
such as urinary tract infection, calculi and masses, have also been eliminated as possibilities
because of the findings on ultrasound and urinalysis. This proteinuria is best characterized as
renal in origin, and given Milly’s previous history of IMHA, the potential of antibody/antigen
complex deposition within glomerular membranes and subsequent glomerular damage would have to be
strongly considered as an underlying mechanism. Recent studies have shown that protein loss
through damaged glomeruli also results in damaged proximal and distal renal tubules resulting in
end-stage kidney disease and increased morbidity in dogs.2
Definitive diagnosis in this case would require renal biopsy with histopathology, which the owner
declined due to the associated risk of the procedure and the patient’s advanced age.
Therapeutic plan Low-protein diet, aspirin 20 mg every 3
days, azathioprine 25 mg every 4 days, enalapril 2.5 mg every other day
Clinical Outcome Milly has continued to do well clinically
on the therapeutic plan. Her urinalysis, UPC, CBC and clinical chemistry are monitored regularly,
thanks to a very compliant and dedicated owner. However, there has been little change in her
laboratory parameters or clinical status over the last several months.
References:
- Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction. 3rd ed.
Philadelphia, Pa: WB Saunders; 2004.
- Jacob F, et al. Evaluation of the association between initial proteinuria and morbidity
rate or death in dogs with naturally occurring chronic renal failure. J Amer Vet Med Assoc.
2005;226:393–400.
Recommended Reading:
- Duncan JR, et al. Veterinary Laboratory Medicine: Clinical Pathology. 4th ed. Ames,
Iowa: Iowa State University Press; 2003.
- Stockham SL, et al. Fundamentals of Veterinary Clinical Pathology. 1st ed. Ames, Iowa:
Iowa State University Press; 2002.
Tell us what you think of this case, or let us know if you have a case that
you would like to submit. E-mail us at
diagnosticedge@idexx.com to get the process started.
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Fort Dodge Animal Health reintroduces ProHeart®
6 in U.S. A quick look at guidelines for use and recommended protocol
ProHeart 6 reintroduced Recently, Fort Dodge Animal Health reintroduced
ProHeart® 6 (moxidectin) to the U.S. veterinary market after a
review by the U.S. Food and Drug Administration’s Center for Veterinary Medicine (CVM). ProHeart
6, a heartworm preventative, was voluntarily recalled by Fort Dodge from the U.S. veterinary
market in September 2004. Based on CVM requirements, Fort Dodge will implement a surveillance
initiative to monitor the safety of ProHeart 6. It will be incumbent upon Fort Dodge to
communicate any reported adverse reactions to the CVM.
Veterinarians who wish to purchase and administer ProHeart 6 must first participate in a Web-based
training program to become registered users. For more information, practitioners are directed to
the Fort Dodge symposium at:
www.vetsymposium.com/proheart6.
Recommended ProHeart 6 protocol According to the guidelines established by
Fort Dodge and approved by CVM, ProHeart 6 may be administered:
- To healthy dogs between six months and seven years of age
- After a thorough history is gathered and a general physical examination is performed by
the veterinarian
- After performing a negative heartworm antigen test, a complete blood count (CBC) that
includes a platelet count and a chemistry panel that includes baseline liver values
Tools to assist with your ProHeart 6 protocols IDEXX Laboratories is pleased
to provide the most comprehensive diagnostics available to comply with and exceed required CVM
guidelines for those practitioners who elect to use ProHeart 6. For in-house use, we recommend a
CBC performed with the LaserCyte®
Hematology Analyzer or the IDEXX VetAutoread™
Hematology Analyzer, combined with a comprehensive chemistry panel, such as the
Diagnostic Health Profile (DHP) on the VetTest®
Analyzer or a Chem 17 on the
Catalyst Dx™ Chemistry Analyzer. In addition, a
SNAP® 4Dx® test
should be run and a complete urinalysis is recommended to allow for interpretation of the renal
panel in the chemistries. A blood film review should be performed as well to detect morphologic
abnormalities.
The DHP is a valuable screen for both the clinically and subclinically sick patient for which the
administration of ProHeart 6 is contraindicated. The DHP
panel includes ALT, GGT, ALB, ALKP and
BUN and provides the most comprehensive patient-side baseline liver values available, not only
fulfilling but surpassing the requirements of the CVM. Comprehensive baseline values will prove
critical should an adverse reaction to ProHeart 6 occur. Lastly, the flexibility of the VetTest
and Catalyst Dx analyzers allows for customized mini panels for more targeted liver testing.
IDEXX Reference Laboratories provides similar comprehensive screens.
For more information about ProHeart 6 or Web registration, visit the Fort Dodge
Animal Health Web site at
www.vetsymposium.com/proheart6. To learn more about the IDEXX instruments and testing
protocols above, visit www.idexx.com/vetlab or
call 1-800-355-2896.
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