25/10/2014

Case Study: Milly, Polyuria and Polydipsia

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Polyuria and Polydipsia

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

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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.

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Differential diagnoses
Diabetes mellitus, diabetes insipidus (central or nephrogenic), chronic renal failure, glomerular disease,
glomerulonephritis, amyloidosis, hyperadrenocorticism, psychogenic polydipsia with medullary washout
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25/10/2014

Case Study: Milly, Polyuria and Polydipsia

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

ErythronThe minimal elevation of MCHC supports the potential of cell-free hemoglobin due to in vitro
or in vivo hemolysis.
LeukonAll 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).
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Case Study: Milly, Polyuria and Polydipsia

ThrombonThere is a minimal and insignificant thrombocytosis present.

Blood film reviewNo significant morphologic abnormalities are noted in any cell line.
Clinical chemistry

Kidney panelThere 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
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Case Study: Milly, Polyuria and Polydipsia

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 ProfileThe 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

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Case Study: Milly, Polyuria and Polydipsia

Abdominal UltrasoundThe 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 immunemediated 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 withinreference-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
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Case Study: Milly, Polyuria and Polydipsia

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 Millys 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 patients 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:
1. Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction. 3rd ed. Philadelphia, Pa: WB Saunders; 2004.
2. 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;226:393400.

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.

The recommendations contained in Diagnostic Edge educational materials are intended to provide general guidance only. As
with any diagnosis or treatment, you should use clinical discretion with each patient based on a complete evaluation of the
patient, including history, physical presentation and complete laboratory data. With respect to any drug therapy or
monitoring program, you should refer to product inserts for a complete description of dosages, indications, interactions and
cautions.

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