Introduction

Polyuria and polydipsia (PUPD) is a common disorder in dogs and cats. As polyuria cannot be easily quantified, the diagnosis mostly relies on daily water consumption. Normal water consumption is ∼50 ml/kg, however, there is great variability among and within species. The definition of polydipsia is met when the daily water consumption is >100 ml/kg. In most of the cases, polyuria is the primary disorder and polydipsia is a compensatory mechanism to maintain normal hydration status. Less frequently, polydipsia is deriving the polyuria (e.g., primary polydipsia, neurological disorders, fever, and pain). The most common mechanisms for polyuria include osmotic (including solute) diuresis, antidiuretic hormone (ADH) deficiency, and conditions that alter the kidney response to ADH. In some disorders the pathophysiology of PUPD is multifactorial, involving both primary polyuria and primary polydipsia.

Establishing Presence of PUPD

In some cases the owners do not recognize PUPD as a problem and in other cases PUPD may be the chief complaint. Incontinence, nocturia, pollakiuria, or inappropriate urination should not be confused with PUPD, therefore, accurate history is informative. Polydipsia can be confirmed easily by measuring daily water consumption. If the latter is not possible, urine specific gravity (USG) can be measured. PUPD is suspected when the morning USG is persistently low. The clinician needs to bear in mind that almost any USG can be normal, depending on the concurrent hydration status of the patient.

Diagnostic Approach

For a rational diagnostic approach, the clinician needs to be familiar with the most common differential diagnoses in which PUPD is the presenting compliant. These include diabetes mellitus, chronic kidney disease (including pyelonephritis), hyperadrenocorticism, liver diseases, central diabetes insipidus (CDI), pyometra, and hypercalcemia. Other differential diagnoses that should be considered, however, PUPD is less likely to be the main presenting compliant, include drug administration (e.g., phenobarbitone, glucocorticoids, diuretics), hypokalaemia, medullary washout, hypoadrenocorticism, congenital nephrogenic DI, post-obstructive diuresis, high salt or low protein diet. Rare differentials should be considered only when the diagnostic work up suggest that these are likely, or when other causes of PUPD have been excluded. These include primary renal glucosuria, Fanconi’s syndrome, and hyperviscosity.

History is an extremely valuable tool to further narrow down the differential diagnosis list, even prior to performing any laboratory test. For example, in a non-spayed female dog that was in estrus in the preceding weeks and also presents systemic clinical signs (e.g., lethargy/anorexia/vomiting), pyometra should be considered high in the differentials. If concurrent history also includes polyphagia, diabetes mellitus, hyperthyroidism (in a cat), and hyperadrenocorticism should be considered. If the latter are also accompanied with weight loss, diabetes mellitus, and hyperthyroidism (cat) should be considered. If the PUPD is accompanied with weight loss, CKD is more likely. Dogs and cats with some diseases are less likely to be bright alert and responsive (e.g., liver failure, hypoadrenocorticism, pyometra, hypercalcemia, advances CKD), whereas in others (e.g., CDI, primary polydipsia) animals are often bright, alert, and responsive, and PUPD is the only clinical sign present.

Physical examination findings may also aid in narrowing down the differential diagnosis list and occasionally be almost indicative of the diagnosis. Presence of anal sac mass in an old dog with PUPD, is highly suggestive of anal sac adenocarcinoma (promoting PUPD due to hypercalcemia). In most cats with hyperthyroidism, a cervical nodule can be palpated. Animals with hyperadrenocorticism, may present with concurrent dermatological disorders (alopecia, thinning of the skin, pot-belly), and animals with diabetes mellitus may present with varying degrees of cataract while small and irregular kidneys are suggestive of CKD.

To reach a final diagnosis, usually ancillary tests are required. Complete blood count, serum chemistry, and urinalysis are indicated in animals presenting with PUPD. Urinalysis is an initial diagnostic test in such cases. The USG is usually iso- to hyposthenuric, but may also be hypersthenuric in animals with diabetes mellitus. Unless USG is very now (<1.006), often times USG by itself does not narrow down substantially the differential diagnoses list. When the urine is extremely diluted, differentials like CDI, hyperadrenocorticism, and primary polydipsia become more likely. Naturally, presence of glucose in the urine is highly suggestive of diabetes mellitus, however, glucosuria may also be present in face of normoglycemia in animals with primary glucosuria, Fanconi’s syndrome, AKI, or in animals with stress/drug induced hyperglycemia. In the latter the glucosuria is expected to be transient. When bacteriuria and pyuria are present in urinalysis, pyelonephritis should be suspected, even in the absence of systemic clinical signs or changes in complete blood count (CBC) or chemistry, and urine should be submitted for culture and sensitivity.

Complete blood count is often times not rewarding, however, it can be used to exclude some differentials (e.g., hyperviscosity) and in some diseases, CBC may increase the suspicion of one differential over the other. For example, stress leukogram and thrombocytosis may imply hyperadrenocorticism. Serum chemistry is extremely useful and in conjunction with the history, physical examination, CBC, and urinalysis findings, further aid in narrowing down the differential diagnosis list. In animals with diabetes mellitus, hyperglycemia is expected. In diabetes mellitus and hyperadrenocorticism, increased activities of liver and biliary enzymes, hypertriglyceridemia, and hypercholesterolemia are expected. In cats with hyperthyroidism, liver enzymes are often elevated. In animals with hypoadrenocorticism, electrolyte disorders (hyponatremia and hyperkalemia) are common and may accompany hypoglycemia, hypocholesterolemia, and hypercalcemia. In animals with kidney disease, creatinine and urea concentrations are often elevated. In animals with liver failure hypoalbuminemia, hypoglycemia, hyperbilirubinemia, hypocholesterolemia, and decreased urea concentration may be identified. Hypercalcemia and hypokalemia can be easily identified as potential causes for PUPD.

Ultrasound examination often completes the initial diagnostic work-up. Hyperthyroid nodules, abnormalities in the adrenal glands, changes in liver and kidneys, should all be assessed.

The above diagnostic work-up is often sufficient to reach a diagnosis, or at least to substantially narrow down the differential diagnosis list. However, in certain occasions, additional tests are required to confirm the diagnosis (T4, hyperadrenocorticism etc.).

In some animals with PUPD, CBC, serum chemistry, urinalysis, and ultrasound examination are completely unremarkable. The main differentials to consider at this point include Stage I CKD (including pyelonephritis), hyperadrenocorticism, diabetes insipidus, and primary polydipsia.

Presence of Stage I CKD can be further evaluated by symmetric dimethylarginine (SDMA) measurement, GFR (endogenous or exogenous creatinine or inulin clearance), and kidney biopsy. Hyperadrenocorticism should be considered even in the absence of any concurrent clinical signs or abnormalities in CBC, serum chemistry, urinalysis, and ultrasound. If the index of suspicion for hyperadrenocorticism is low, urine cortisol to creatinine ratio (from voided urine sample obtained by the owners at home) can be used to exclude the disease. However, if the result is abnormally high, this test cannot confirm the diagnosis, and further tests like low dose dexamethasone suppression test and ACTH-stimulation test should be pursued.

In cases where all previously mentioned diagnostic tools were negative, the main remaining differentials include primary polydipsia and diabetes insipidus. In theory, calculated or measured serum osmolality can be used to differentiate these conditions, as in primary polydipsia, the polydipsia is deriving polyuria and thus serum osmolality is expected to be low, whereas in diabetes insipidus, the polyuria is deriving the polydipsia and thus the serum osmolality is expected to be high. In reality, compensatory mechanisms (i.e., drinking and urination) offset the primary mechanism for PUPD, and serum osmolality remains within the reference interval. Water deprivation test was previously suggested to differentiate primary polydipsia and diabetes insipidus and further to differentiate central vs. nephrogenic diabetes insipidus. However, this test is not risk free and thus, unless primary polydipsia is highly suspected (young, active dogs), this test is mostly replaced by an ADH trial. In this test, ADH is administered (orally or to the conjunctival sac) after the owners have quantified and established the daily water consumption. Water quantification should be continued daily after ADH administration. A 50% decrease in water consumption is confirmatory for the diagnosis of CDI. A common mistake is to rely on spot USG to confirm the diagnosis. One has to consider that often times, the change in urine USG on a spot sample may not be very different from the baseline, as the administered ADH is not active throughout the day, and when the serum ADH is low, the urine is quickly diluted and a large volume of highly diluted urine masks the transient increase in urine USG.