Here is an information sheet from VIN that discusses PU/PD.:

There are  at least 25 different thing to rule out. And, unfortunately, many dvm’s jump right to DI. Hopefully you will see that DI is not always on the top of the list. A lot of testing has to “pass under the bridge” before we “diagnose” DI. If she does have it, however, there may be some tweaking that can be done.
Linda G. Shell, DVM, DACVIM (Neurology)

Disease description:
Before diagnostic procedures are undertaken to determine the etiology of polydipsia/polyuria (PD/PU), it is necessary to consider the definitions of each and to try to determine if the patient is truly PD/PU.
# Polydipsia in the cat and dog is the consumption of greater than 100 ml/kg of water per day or approximately 2 ml/lb/hour. Sick animals and animals with dysphagia may visit the water bowl frequently without imbibing water so it may become important to measure water intake at some point.
# Polyuria in the cat and dog is the production of greater than 50 ml/kg (23 ml/lb) of urine per day or more than 2.2 ml/kg/hr (1 ml/lb/hr). Evaluation of several urine specific gravities will allow one to establish if the patient is polyuric or not. If the specific gravity is > 1.030, it is very unlikely that the patient is urinating
or drinking excessively. If the urine specific gravity is persistently less than 1.020, it is more likely that the patient is polyuric. # Pollakiuria, the urge to urinate frequently, may be confused with polyuria. Pollakiuria may result from an irritation of the urinary tract and not from increased amounts of urine.

After confirming the the patient is PU/PD, it is helpful to try to determine if the patient has primary polydipsia which results in compensatory polyuria, or if the patient has primary polyuria which results in compensatory polydipsia. The rule outs are different for primary polydipsia vs primary polyuria. History and initial laboratory data should be helpful to distinguish between the two mechanisms.

Mechanisms causing Polydipsia:
Polydipsia is usually compensation for increased water loss primarily due to polyuria. However there are conditions causing polydipsia which then result in compensatory polyuria. These conditions are psychogenic polydipsia, hypothalamic injury, certain foods (salt), hypercalcemia, hyperreninemia, excessive exercise, and hot weather. If polydipsia is the cause of the polyruria, one would expect to find normal to low serum sodium and low serum osmolality.

Mechanisms causing Polyuria:
There are two major mechanisms producing polyuria:
1) Water diuresis is the excessive production of low specific gravity urine.
2) Solute diuresis is due to the development or intake of excessive solute.

Causes of water diuresis:
# Diabetes insipidus: Central (decreased production of vasopressin (ADH)) or nephrogenic (decreased ADH receptors or decreased sensitivity to ADH in the renal tubules) diabetes insipidus causes PU/PD.
# Hyperadrenocorticism results in excessive amounts of cortisol that can block the effect of ADH on renal tubules.
# Hypoadrenocorticism causes loss of sodium, the major medullary solute. Hyperkalemia may interfere with ADH function.
# Escherichia coli infections, as seen with some pyometras, often produce endotoxins believed to interfere with ADH activity.
# Psychogenic polydipsia increases fluid load promoting diuresis. It may result in renal medullary solute washout. Polydipsia as the primary cause of PU/PD is not as common as polyuria. Psychogenic polydipsia can be induced by stress. Damage to the hypothalamus may overstimulate the thirst center. Certain foods (salty, spicy) encourage excessive intake of fluids.
# Hepatic failure can produce PU/PD via poorly understood mechanisms. Theories include an increase in glucocorticoids, mineralocorticoids, or renin. Another theory is that there is decreased ammonia conversion to urea, a major medullary solute.
# Hypokalemia interferes with renal tubular function and ADH sensitivity. It can be caused by chronic renal disease, excessive use of furosemide, and nutritional deficiency.
# Hyperthyroidism promotes diuresis by increasing sensitivity to catecholamines, increasing renal medullary blood flow and medullary washout. Hyperthyroidism is uncommon in the dog, but common in the cat.
# Hypercalcemia associated with malignancy, cholecalciferol toxicity, or hypoadrenocorticism can cause renal damage or interfere with ADH function.
# The use of diuretics, certain drugs, and intravenous fluid therapy promote diuresis.
# Pheochromocytomas are catecholamine producing tumors that produce PD/PU by increasing renal medullary blood flow and medullary solute washout.
# Polycythemia may produce PD/PU by causing a decrease in ADH production.

Causes of solute diuresis:
# Diabetes mellitus produces glucosuria which results in diuresis.
# Renal glucosuria without hyperglycemia can produce diuresis. Renal glucosuria can be caused by congenital, chemical, or inflammatory etiologies.
# Correction of urinary obstruction can produce a sudden release of solutes which promotes diuresis and possibly medullary washout.
# Intravenous infusion with hypertonic solutions such as glucose or saline can produce diuresis.

Causes of combined solute and water diuresis:
# Renal disease can cause medullary solute washout resulting in water diuresis or large solute excretion from remaining functional nephrons, which results in solute diuresis.
# Excessive growth hormone (acromegaly) may produce solute diuresis by creating a resistance to insulin (diabetes mellitus). It may also interfere with the production of ADH producing a water diuresis.

Pathophysiology of fluid regulation:
Fluid regulation in the dog and cat is the result of a delicate balance achieved by the combined activities of hormones, neural activity, and kidney function. Changes in plasma osmolality is detected by the osmoreceptors in the hypothalamus. Changes in certain plasma solutes (sodium, mannitol, and sucrose) and changes in blood volume or pressure influence the release of vasopressin, the antidiuretic hormone (ADH). Vasopressin (ADH) is produced in the supraoptic and paraventricular nucleus of the hypothalamus and is carried to the neurohypophysis (posterior pituitary) by way of nerve fibers (axons) for storage. Other
factors can also influence the secretion of ADH such as nausea, hypoglycemia, the renin-angiotensin system, body temperature, some drugs, and stress factors. ADH acts to inhibit water loss from the body by increasing the permeability of the distal and collecting tubules of the kidney. Medullary hypertonicity then draws solute free water of the renal tubules into the medullary interstitium and blood stream by an osmotic gradient. ADH is degraded and removed probably by both kidney and liver.

The renin-angiotensin-aldosterone (RAA) mechanism is the next important regulator of fluid balance. Decreased circulation and blood pressure to the kidneys stimulates the release of renin from the juxtaglomerular cells of the kidney. Renin release activates angiotensinogen, produced in the liver, converting it to angiotensin I. Angiotensin I in the lung and probably other vascular areas of the body is acted on by the angiotensin converting enzyme and converted to angiotensin II. Angiotensin II results in arteriolar vasoconstriction, increased thirst, sodium retention, and stimulation of the release of aldosterone from the adrenal cortex. Aldosterone inhibits the loss of sodium from the body, simultaneously reducing water loss and encouraging potassium loss.

The osmoreceptors of the hypothalamus, when triggered by increased blood osmotic pressure or damage, stimulate the thirst center of the hypothalamus encouraging the intake of water by the animal.

Medullary solute washout, induced by severe diuresis of any etiology, results in the removal of solutes (mainly sodium and urea) needed to maintain medullary hypertonicity. Medullary hypertonicity is one of the mechanisms necessary for ADH function.

*Central diabetes insipidus
*Fanconi syndrome
*Fluids administered
*Liver disease
*Post obstructive diuresis
*Renal diabetes insipidus
*Renal failure
*Renal glycosuria
*Renal medullary solute washout
*Sodium bicarbonate
*Thyroid hormones
Amphotericin B
Diabetes mellitus

Clinical findings:
Cachexia, weight loss
Onset gradual, slow
s: Diagnostic results:
Low dose DXM test of plasma, 0 & 8 hr post DXM Baseline increased and
lack of cortisol suppressioon low dose DMX

Hemogram Hemoconcentration or polycythemia
Rubricytes increased

Serum chemistry Alanine aminotransferase increased
Alkaline phosphatase increased
Aspartine aminotransferase increased
Blood urea nitrogen (BUN) increased
Creatinine clearance decreased
Gamma-glutamyl transferase (GGT) increased
Hyperglycemia, blood glucose increased
Lipidemia, lipids increased

Urinalysis and Urine Sedimentation Bacteriuria, urine bacteria increased
Isosthenuria, Urine Sp. G. fixed (1.007-1.017)
Proteinuria, albuminuria

Anion gap calculation of serum Anion gap increased

Cortisol levels of plasma Cortisol increased

Cortisol:creatinine ratio of urine Cortisol, creatinine ratio > 35

Endogenous ACTH levels of frozen plasma ACTH levels decreased (Adrenal mediated)
Endogenous ACTH increased with pituitary dependent hyperadrenocorticism

High dose dexamethasone test on plasma 0 & 8 hr post dexamethasone
Cortisol increased initially, suppresses to less than 50 % with pituitary dependent hyperadrenocorticism.

Protein and creatinine assays of urine Urine protein:urine creatinine ratio >1

Water deprivation test Water deprivation decreased Sp. G.

Plasma osmolality Urine osmolality:plasma osmolality >1

Computer assisted tomography (CAT) of head, abdomen Pituitary or adrenal tumor

Direct blood pressure recording Blood pressure increased > 150/90

1) Treatment depends on the etiology. After the diagnostic procedures have been performed, consult the specific disease for treatment.

Special considerations:
Diagnostic procedures should be performed in an orderly progression, but base priorites on the information obtained from the history and initial minimum data base tests.

Importance of age/sex:
1) Pups with PD/PU: Consider congenital disease, renal malformation, congenital diabetes insipidus, portosystemic shunt, hypoadrenocorticism.
2) Middle aged or older intact bitches with PU/PD: Consider pyometra, renal disease, liver disease, hyperadrenocorticism.
3) Middle aged or older spayed females with PU/PD: Stump pyometra is still a possibility, diabetes mellitus, as well as the previous diseases mentioned for intact females.
4) Middle aged or older intact males with PU/PD: Consider prostatitis and subsequent pyelonephritis, renal disease, liver disease, hyperadrenocorticism.
5) Older animals with PU/PD: Consider renal disease, liver disease, hypercalcemia of malignancy.

Importance of breed:
1) German shepherd or any large breed, nervous dog: Predilection for psychogenic polydipsia
2) Lhasa apso, Shih Tzu, cocker spaniel, Basenji, and many other breeds: Predilection for congenital renal dysplasia.
3) Norwegian elkhound, Scottish terrier: Predilection for renal glycosuria.

Importance of history:
1) If signs appear in animals that are prone to roaming, consider cholecalciferol poisoning and other poisons.
2) Head trauma can cause PD/PU.
3) Many medications and fluid administration can cause PD/PU. If diuretics, glucose, or fluid therapies have been previously administered, consider renal medullary solute washout. Aminoglycoside administration can cause tubular nephrosis. Phenobarbital and bromide often cause PU/PD as does corticosteroids, even topically applied ones.
3) Fever may result in PU/PD.
4) Recently relieved urinary tract obstruction may result in post obstructive diuresis.
5) Polyphagia in conjunction with PU/PD, panting, or a pot-belly appearance suggests hyperadrenocorticism, particularly in middle-aged to older dogs.
6) Vaginal discharge suggests possibility of pyometra.
7) Foul smelling urine and pyuria suggests cystitis which may have resulted in pyelonephritis.
8) Foul smelling breath or a brown discharge on teeth suggests uremia as a possibility.
9) If glucosuria is present consider diabetes mellitus, Fanconi syndrome, renal glycosuria, hyperadrenocorticism, or glucose administration. Check for hyperglycemia.
10) A history of vomiting suggests hypoadrenocorticism, liver, or renal disease as possibilities. If bradycardia is present, check for hypoadrenocorticism first.

Diagnostics – first tier tests:
# History: A competent history will eliminate iatrogenic, dietary, climatic, drugs, and post obstructive diuresis as causes of PD/PU.
# Urinalysis should be the first test done to determine if the urine specific gravity fits with the history of PU/PD.# Complete blood count is part of minimum data base and will help to eliminate polycythemia as well as may yield clues for other disease processes (example: eosinophilia and lymphocytosis may occur with
# Electrolytes and chemistry values will help to eliminate diabetes mellitus, hypercalcemia, hypokalemia, and renal failure.
# Urine culture should be done to rule in pyelonephritis. A negative culture doesn’t necessarily eliminate pyelonephritis however.
# Plasma osmolality: This is an optional test in the preliminary work-up that can often distinguish between primary polydipsia (increased drinking = decreased to normal plasma osmolality with compensatory PU) and primary polyuria (obligatory loss of water = normal to increased plasma osmolality with compensatory PD).
# Which tests to perform next depends on the signalment, history, and the results of blood work and urinalysis. Thus the following list of diagnostic tests is not necessarily in order for your particular case.

Diagnostics – second tier tests:
# Pre and post bile acids should be considered if the BUN, cholesterol, liver enzymes, and albumin are low normal to below normal or if there is a history of clinical signs that fit with hepatic encephalopathy.
# ACTH testing should be considered if hypoadrenocorticism or hyperadrenocorticism is a possibility.
# A serum resting cortisol level may be able to eliminate hypoadrenocortism as an etiology.
# A low dose dexamethasone test should be considered if hyperadrenocorticism is a consideration.
# A resting T4 is needed if the patient is a cat or an older dog or a dog on thyroid supplementation.
# Ultrasound of the uterus, adrenals, liver, and kidneys may be helpful.
# Computed tomography or magnetic resonance imaging of the brain is only done if a hypothalamic lesion is suspected to be causing the PU/PD.
# Renal clearance tests or biopsy may be necessary to show decreased renal function in animals that have PU/PD without azotemia. PU/PD can be present when 2/3 of nephrons are damaged whereas azotemia isn’t present until 3/4 of the nephrons are damaged.

Diagnostics – third tier tests:
# Modified water deprivation test (MWDT) is put on this level of diagnostics as it usually one of the very last tests to consider doing in a PU/PD case. Do not perform a MWDT if azotemia, dehydration, hypercalcemia or significant systemic disease is present. The MWDT is safer than the water deprivation test. More details about how to perform and interpret the MWDT can be found here.
# Water deprivation test (WDT) is considered dangerous and should be used only with great caution and understanding of the test. It is never warranted (and is contraindicated) if there is dehydration, increased plasma hyperosmolality, hyperglycemia, hypercalcemia, or azotemia. More details about how to perform and interpret the WDT can be found here.

1) Taylor SM: Polyuria and polydipsia. Textbook of Small Animal Internal Medicine, 5th ed. Philadelphia, WB Saunders 2000 pp. 85-89.
2) Steele J: The Diagnostic Approach to PU/PD. VIN Rounds 2007.
3) Feldman EC: Polyuria and Polydipsia (VET-137a). Western Veterinary Conference 2004.
4) Hoskins JD: Pediatric Renal Disease (VET-315). Western Veterinary Conference 2004.
5) Bennett P: Polyuria and Polydipsia. Australian College of Veterinary Scientists Science Week 2003.
6) Bartges J: H2O or K9P? Polyuria and Polydipsia. ACVIM Proceedings 2003.
7) Diabetes Insipidus and Other Causes of Polyuria/Polydipsia: Behrend EN. Western Veterinary Conference 2003.
8) Nelson RW: Polyuria, Polydipsia and Diabetes Insipidus. WSAVA Congress 200.
9) Bruyette D: Diagnostic Approach to Polyuria And Polydipsia. Atlantic Coast Veterinary Conference 2002.

Dr. Kathy
Redford, MI