Polyuria\/polydipsia (PU\/PD) is a common reason for dogs and cats to present to a veterinarian. With over 30 causes of PU\/PD, the diagnostic workup can be challenging for both the clinician and the client. This article explains the mechanisms behind increased urination and thirst and provides a stepwise diagnostic approach. By approaching PU\/PD mechanistically, clinicians can use key findings such as urine specific gravity and plasma sodium concentrations to prioritize the differential list and streamline the diagnostic approach.<\/p>\n
Take-Home Points<\/strong><\/p>\n Polyuria and polydipsia (PU\/PD) are common chief complaints for dogs and cats presenting to a veterinarian. With more than 30 causes of PU\/PD (<\/span>TABLES 1 AND 2<\/b><\/span>), the diagnostic workup can be challenging.1-24<\/sup> By taking a mechanistic, stepwise diagnostic approach, veterinarians can use key features such as urine specific gravity (USG) and serum biochemical profile findings to determine which mechanism is responsible for PU\/PD, thus greatly narrowing the differential list for a polyuric\/polydipsic patient.<\/span><\/p>\n With the root word \u201cpoly\u201d meaning \u201cmany,\u201d it follows that polyuria is the excessive secretion of urine and polydipsia is excessive thirst. More specifically, polyuria is the conscious<\/i> voiding of large<\/i> amounts of urine that is unrelated to urinary tract signs. Polydipsia and polyuria are defined as water intake that exceeds 100 mL\/kg per day and urine output that exceeds 50 mL\/kg per day, respectively.1<\/sup> Clinically, water intake can be highly variable and depends on environment, activity level, and diet.25-27<\/sup> Clients may find it difficult to measure water intake in their pet, especially in multipet households, and reliable quantification of urine output is almost impossible to achieve in a nonhospital setting. Furthermore, as baseline water intake and urinary bladder capacity can be highly variable, a patient can be clinically polyuric or polydipsic without exceeding the limits defined by polyuria and polydipsia.28<\/sup><\/span><\/p>\n Although a client may observe that their pet either drinks or urinates excessively, it is not possible for polyuria or polydipsia to persist without the other. Therefore, PU\/PD is approached as a single medical problem. It is important to note that the client observation of a pet urinating more than usual is not always PU\/PD. For example, the owner of a dog with pollakiuria secondary to a urinary tract infection may describe their pet as urinating a lot. Similarly, the owner of a dog with urinary incontinence may describe excessive urination. These two \u201clook-alikes\u201d have very different differential lists and workups. Therefore, it is imperative to collect a complete history that allows for differentiation between PU\/PD, pollakiuria, and urinary incontinence. In collecting a history on a patient presenting for excessive urination, questions should be targeted to determine the volume, frequency, and timing of urination (<\/span>BOX 1<\/b><\/span>). If there is evidence of pollakiuria, hematuria, stranguria, dysuria, or periuria, lower urinary tract disease should be investigated.\u00a0<\/span><\/p>\n In assessing USG, it is important to consider what is appropriate rather than what is normal. For example, a low USG is expected in patients receiving certain medications (e.g., glucocorticoids, diuretics) and is an expected physiologic response after a dog or cat drinks a large amount of water, while a low USG in a patient that is visibly dehydrated indicates obligate polyuria (inability to concentrate urine). <\/span><\/p>\n First morning urine samples are often recommended for determination of maximum urine concentrating ability, as it is thought most patients consume less water overnight. However, USG can vary considerably in healthy animals, even with first morning urine samples.29,30<\/sup> The presence of large amounts of protein or glucose can also alter the USG. Each gram of glucose per deciliter increases the USG of canine urine by 0.002 to 0.004 and feline urine by 0.007 to 0.008.31<\/sup><\/span><\/p>\n Urine may be described as well concentrated (hypersthenuric), moderately concentrated, isosthenuric, or dilute (hyposthenuric).32<\/sup> The prefixes \u201chypo,\u201d \u201ciso,\u201d and \u201chyper\u201d are used to compare urine osmolality to plasma osmolality (290 to 310 mOsm\/kg).33<\/sup> Although USG is not correlated to a specific diagnosis, it can be helpful in prioritizing differentials in the workup of a patient with PU\/PD (TABLE<\/b><\/span><\/span>\u00a03<\/b><\/span>).<\/span><\/p>\n Understanding how urine is concentrated can help in understanding the mechanisms by which PU\/PD may occur. There are 6 requirements to make concentrated urine: functional nephrons, generation and preservation of a renal corticomedullary gradient, appropriate renal tubular filtrate osmolality, production and release of antidiuretic hormone (ADH), response to ADH at the level of the renal tubule, and appropriate water intake. PU\/PD results from disruption in 1 or more of these requirements (TABLE<\/b><\/span><\/span>\u00a04<\/b><\/span>).<\/span><\/p>\n As the functional units of the kidney, nephrons are key to urine concentrating ability. It is important to recognize that urine concentrating capacity is lost before the ability to excrete metabolic wastes. Generally, urine concentrating ability is considered compromised once approximately two-thirds of total nephron function is lost, with azotemia reflecting a loss of three-quarters of overall nephron function.32<\/sup> <\/span><\/p>\n Loss of functional nephrons is one of the mechanisms by which chronic kidney disease (CKD)\u2014and in the early stages, acute kidney injury\u2014causes PU\/PD. The loss of functional nephron mass that occurs with CKD can cause polyuria without azotemia being appreciated on blood analysis. However, unlike dogs, cats with CKD may retain the ability to concentrate their urine as high as a USG of 1.040 or 1.045 and therefore can be azotemic without significant PU\/PD.32<\/sup><\/span><\/p>\n To allow water to be conserved from the renal tubular filtrate, a hypertonic medullary interstitium must be maintained. In healthy animals, the glomerular filtrate entering the renal tubule is at an osmolality similar to plasma (290 mOsm\/L). The difference in osmolality between the medullary interstitium and renal tubular filtrate creates a gradient for passive reabsorption of water in the descending loop of Henle and sodium chloride without water in the thin ascending loop of Henle. The medullary gradient is created by the concentration of sodium and urea within the medullary interstitium through the countercurrent exchange mechanism. ADH, which is released by the posterior pituitary in response to increasing plasma osmolality, stimulates urea transporters within the kidney, resulting in a fourfold increase in urea reabsorption and concentration within the medullary interstitium.33<\/sup> Consequently, the hypertonicity of the medullary interstitium is maximized in the presence of ADH.<\/span><\/p>\n Diseases characterized by low urea, such as congenital portosystemic shunts and liver dysfunction, can cause PU\/PD from medullary washout. Similarly, ultra\u2013low-protein diets, such as those used for urolith dissolution, can cause PU\/PD secondary to low blood urea nitrogen (BUN) concentrations. Diseases that cause hyponatremia, such as hypoadrenocorticism (Addison\u2019s disease), can also cause PU\/PD from loss of the hypertonic medullary interstitium. Renal tubular disease or administration of loop diuretics may result in decreased transport of sodium and chloride from the ascending loop of Henle to the medullary interstitium, causing PU\/PD.<\/span><\/p>\n It is also important to recognize that increased rates of renal tubular flow may not afford enough time for creation of the medullary osmotic gradient. As few as 3\u00a0days of polyuria may result in medullary washout due to impaired reabsorption of sodium, chloride, and urea. Therefore, dogs with primary (psychogenic) polydipsia may be unable to concentrate their urine following water deprivation and should not be mistaken as having obligate polyuria.<\/span><\/p>\n The passive absorption of water and sodium chloride within the renal medulla depends on the osmolality of the renal tubular filtrate. Should the renal tubular filtrate have a higher osmolality, the gradient between the renal tubular fluid and medullary interstitium may no longer facilitate passive reabsorption of water and solutes. <\/span><\/p>\n Osmotic diuresis occurs when a substance of high molecular weight, such as glucose or mannitol, enters the kidney tubules, increasing the osmolality of the renal tubular filtrate. Consequently, patients with glucosuria, whether secondary to diabetes mellitus or primary renal glucosuria, may have profound PU\/PD.<\/span><\/p>\n In healthy animals, the amount of water the kidneys secrete depends on the body\u2019s osmolality. Control of body fluid tonicity, or osmoregulation, is necessary to maintain cell volume and function, as cells are in osmotic equilibrium with the fluid that surrounds them. Consequently, the body aims to maintain a narrow range of osmolality. When plasma osmolality (sodium concentration) increases, cells in the hypothalamus known as osmoreceptors shrink, causing the release of ADH from the posterior pituitary.1<\/sup> ADH is the primary regulator of renal water excretion. When it is present, ADH increases the water permeability of the luminal membrane of the renal collecting ducts through the insertion of water channels known as aquaporins. However, it must first be produced in response to increasing plasma osmolality.<\/span><\/p>\n Central diabetes insipidus (CDI) refers to polyuric syndromes that result from lack of sufficient ADH to concentrate urine for water conservation. The production and release of ADH from the hypothalamus and pituitary, respectively, can be affected by any disease that damages these areas in the brain, including head trauma, neoplasia, hypothalamic or pituitary malformations, cysts, inflammation, and parasite migration. However, idiopathic CDI is most common. Patients with complete ADH deficiency (i.e., complete CDI) are profoundly polyuric\/polydipsic, producing hyposthenuric urine. However, the finding of isosthenuria or minimally concentrated urine does not rule out the possibility of CDI, as dogs and cats can develop partial CDI.<\/span><\/p>\n After being released, ADH travels through the bloodstream to act on vasopressin receptors in the renal collecting ducts. ADH binding to its receptor results in the translocation and insertion of aquaporin-2 channels, which allow water to be passively reabsorbed down its concentration gradient into the bloodstream. <\/span><\/p>\n Failure of the nephron to respond to ADH (nephrogenic diabetes insipidus [NDI]) can occur as a <\/span>primary disease (extremely rare) or secondary to another disease. Secondary NDI can be caused by glucocorticoids (endogenous or exogenous), hypercalcemia, Escherichia coli<\/i> endotoxin, leptospirosis, hypokalemia, and intestinal leiomyosarcoma. The most common cause of a secondary NDI in dogs is hyperadrenocorticism (Cushing\u2019s disease or hypercortisolism).<\/span><\/p>\n Increased water intake leads to a compensatory, appropriate polyuria to excrete the excess water. Therefore, urine concentration necessitates that the patient is drinking an appropriate amount of water for its physiologic demands. <\/span><\/p>\n Primary polydipsia may be a psychologic or behavioral problem and therefore is often termed psychogenic polydipsia. <\/i>However, primary polydipsia can also be a manifestation of hepatic encephalopathy, gastrointestinal disease, or hyperthyroidism.<\/span><\/p>\n The diagnostic approach to the polyuric\/polydipsic patient can <\/span>vary considerably depending on the patient\u2019s signalment, history, and concurrent clinical signs. The following is a general stepwise approach to a patient with PU\/PD. It should be recognized that the workup of a polyuric\/polydipsic patient is not always linear, with some diagnostic tests being prioritized over others based on the patient\u2019s signalment and concurrent clinical signs. For example, in a dog presenting with PU\/PD, polyphagia, and weight loss, it would be appropriate to start by looking for diabetes mellitus. <\/span>FIGURE 1<\/b><\/span> provides a visual schematic; however, the decision tree for a patient with PU\/PD hinges on interpreting the signalment, history, imaging, and clinicopathologic findings as a whole. TABLES<\/b><\/span><\/span> 1 AND 2<\/b><\/span> provide a summary of the reported causes of PU\/PD in dogs and cats.<\/span><\/p>\n A good diagnostic workup begins with the collection of a thorough history (<\/span>BOX 1<\/b><\/span>). The first step is to determine if the patient is presenting with PU\/PD, pollakiuria, or urinary incontinence, as the workup of each is quite different. Given that endocrinopathies are relatively common causes of PU\/PD, the history and physical examination should be directed at screening for diseases such as hyperadrenocorticism, diabetes mellitus, and hyperthyroidism. For example, hyperthyroidism and diabetes mellitus should be considered in a cat presenting with PU\/PD and concurrent weight loss in the face of polyphagia. <\/span><\/p>\n Many medications can interfere with the concentration of urine; thus it is important to collect a complete medication history, including the use of diuretics and corticosteroids. Dogs with hypothyroidism being treated with levothyroxine should be assessed for over-supplementation. Diet history is also important. Low-protein diets, such as urolith dissolution diets, can impair renal concentrating ability by depleting renal medullary urea concentrations. High-sodium or high-osmolality diets (e.g., some hydrolyzed diets) may also induce polydipsia. <\/span><\/p>\n A thorough physical examination is important to evaluate for systemic disease, causes of PU\/PD, and consequences of polyuria (e.g., urine scald). A rectal examination should be performed on every dog with PU\/PD to evaluate for an anal sac tumor, as 27% to 53% of patients with apocrine gland anal sac adenocarcinomas have paraneoplastic hypercalcemia.34<\/sup> The finding of peripheral lymphadenopathy on a physical examination should prompt fine needle aspiration given concerns for lymphoma resulting in hypercalcemia. Abdominal palpation may reveal splenomegaly, abdominal masses, or abdominal pain, which may help prioritize differential lists and direct diagnostic investigations. With hyperadrenocorticism being a common cause of PU\/PD in dogs, the presence of a potbelly, hepatomegaly, and\/or truncal alopecia should be noted. In cats, palpate for a thyroid goiter.<\/span><\/p>\n The USG is critical to narrow the differential list and direct diagnostics (TABLES<\/span><\/b><\/span> 3 AND 4<\/b><\/span>). Urine culture is also indicated in all animals with PU\/PD, as they are prone to urinary tract infections. Furthermore, bacterial pyelonephritis can cause secondary NDI, leading to hyposthenuria and PU\/PD. If there is an active urinary tract infection, antibiotics based on culture and sensitivity should be prescribed and the patient reevaluated following treatment. <\/span><\/p>\n Pyelonephritis is suspected when there are azotemia, fever, painful kidneys, and sonographic changes (e.g., renal pyelectasia, hyperechoic renal cortices, hyperechoic perirenal mesentery), even if the urine culture is negative. Care should be taken to not overinterpret renal pelvic dilation as it can be seen in normal animals, patients on intravenous fluids, or patients with any cause of polyuria.<\/span><\/p>\n If glucose is present in the urine, peripheral blood glucose should be evaluated and compared to the species\u2019 renal threshold. In healthy animals, 100% of plasma glucose is filtered into the renal tubular filtrate and reabsorbed by proximal renal tubule cells. The renal threshold for glucose defines the capacity of the renal proximal tubular cells to reabsorb glucose. If the blood glucose exceeds the renal threshold (>180 mg\/dL in dogs, >270 mg\/dL in cats), glucosuria is expected.8,35<\/sup> PU\/PD in a patient with diabetes mellitus is due to persistent hyperglycemia that exceeds the renal threshold and spills over into the urine. However, in the patient with glucosuria and a peripheral blood glucose that is consistently <\/i>less than the renal threshold, causes of primary renal glucosuria or acquired renal tubulopathy (e.g., jerky treats, copper-<\/span>associated hepatitis, drugs\/toxins) should be investigated.<\/p>\n Although proteinuria is clinically significant, it is not in itself a cause of polyuria. The presence of proteinuria in a polyuric\/polydipsic patient should prompt closer investigation for pyelonephritis, CKD, proximal renal tubular damage, or hyperadrenocorticism. For more information on proteinuria, see <\/span>todaysveterinarypractice.com\/urology-renal-medicine\/clinical-approach-to-proteinuria<\/span><\/a>. <\/span><\/p>\n After evaluating the urine, a complete blood count and serum biochemical profile with electrolytes should be performed to round out the minimum database. Evidence of an inflammatory leukogram should prompt investigation for infections (e.g., pyelonephritis, pyometra, prostatitis, leptospirosis). Although the entire profile should be evaluated, close attention should be paid to the electrolytes to screen for hypercalcemia, hypokalemia, and hyponatremia; the kidney values (BUN, creatinine); and the hepatic synthetic parameters (BUN, albumin, cholesterol, and glucose). Total hypercalcemia should prompt evaluation of ionized calcium. Further investigation of hypercalcemia includes repeating the physical examination, screening for endocrinopathies such as hyperadrenocorticism, and evaluating a parathyroid hormone\/parathyroid hormone\u2013related protein\/ionized calcium panel.<\/span><\/p>\n Endocrine disease (e.g., hyperadrenocorticism, hyperthyroidism, diabetes mellitus) is one of the most common causes of PU\/PD in dogs and cats. Therefore, when the signalment, history, and physical examination are suggestive of an endocrine disease, appropriate testing should be performed. Adult cats with PU\/PD warrant assessment of a total T4 (thyroxine) test, and adult dogs with PU\/PD warrant testing for hyperadrenocorticism (e.g., adrenocorticotropic hormone stimulation test, low-dose dexamethasone suppression test). For more information on testing for hyperadrenocorticism, see <\/span>todaysveterinarypractice.com\/endocrinology\/the-diagnosis-of-canine-hyperadrenocorticism<\/span><\/a>. It is important to recognize that dogs with hyperadrenocorticism can respond to a desmopressin trial (see STEP<\/strong><\/span><\/span>\u00a08<\/b><\/span>) but should be screened for this disease before performing a desmopressin trial. <\/span><\/p>\n Although 20% of hypoadrenocorticism cases have PU\/PD, their USG is generally in the isosthenuric range due to medullary washout (hyponatremia) or concurrent CKD, and consequently they tend to not have PU\/PD as profound as that seen with hypercalcemia and hyperadrenocorticism. <\/span><\/p>\n Hypothyroidism does not<\/i> cause PU\/PD; however, dogs treated with thyroxine may develop iatrogenic hyperthyroidism. Naturally occurring hyperthyroidism is uncommon in dogs and is usually associated with a palpable thyroid mass. <\/span><\/p>\n Given that loss of urine concentrating ability often precedes azotemia, patients with CKD may present with PU\/PD in the absence of measurable azotemia. This is more common in dogs, as cats frequently maintain concentrating ability in early CKD, such that azotemia is often present when clinical PU\/PD becomes apparent. However, in the polyuric\/polydipsic dog, ruling out early, nonazotemic CKD can be challenging. There are some hints that can help determine if early CKD is present. Unlike other causes of PU\/PD that are driven by changes in hormone or solute concentrations that can fluctuate, CKD is typically characterized by a relatively static USG that is often isosthenuric to minimally concentrated. <\/span><\/p>\n Biomarkers for glomerular filtration rate (GFR) such as symmetric dimethylarginine (SDMA) have been proposed, with studies documenting increases above the reference interval (>14 \u00b5g\/dL) with 49% nephron loss.36<\/sup> However, it has been the author\u2019s experience that although SDMA shows promise in a population setting, individual variability makes it challenging to use as a rule-in or rule-out test for CKD. <\/span><\/p>\n Imaging of the kidneys can also be helpful, particularly in young dogs with possible renal dysplasia; however, sonographic changes are not indicative of kidney function. Thus, if a dog with PU\/PD is noted to have consistently isosthenuric to minimally concentrated urine, measurement of GFR should be considered. GFR may be assessed by iohexol clearance, endogenous or exogenous creatinine clearance, or nuclear scintigraphy.37,38<\/sup><\/span><\/p>\n In a systemically ill patient with PU\/PD, or after evaluating for the more common causes of PU\/PD in a stable patient, additional diagnostics such as imaging, infectious disease testing, and liver function testing are indicated based on the patient\u2019s signalment, environment, history, concurrent clinical signs, physical examination, and clinicopathologic findings. <\/span><\/p>\n Leptospirosis Testing<\/b><\/p>\n\n
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<\/a><\/p>\n<\/a><\/p>\nDefining Polyuria and Polydipsia<\/h2>\n
Identifying Polyuria and Polydipsia<\/h2>\n
\n
The Importance of Urine Specific Gravity<\/h2>\n
<\/a><\/p>\nNormal and Abnormal Urine Concentration<\/h2>\n
<\/a><\/p>\nNephron Function<\/h3>\n
Renal Corticomedullary Gradient<\/h3>\n
Renal Tubular Filtrate Osmolality<\/h3>\n
Antidiuretic Hormone Production<\/h3>\n
Response to Antidiuretic Hormone<\/h3>\n
Water Intake<\/h3>\n
Diagnostic Approach to the Polyuric\/Polydipsic Patient<\/h2>\n
<\/a><\/p>\nSTEP 1:<\/b><\/span> Collect a Complete History and Confirm Consistency With PU\/PD<\/h3>\n
STEP 2:<\/b><\/span> Perform a Thorough Physical Examination<\/h3>\n
STEP 3:<\/b> <\/span>Evaluate the Urine (Urinalysis and Urine Culture)<\/h3>\n
STEP 4:<\/b><\/span> Complete a Minimum Database<\/h3>\n
STEP 5:<\/b> <\/span>Screen for Endocrine Diseases<\/h3>\n
STEP 6:<\/b><\/span> If Concerns for CKD Exist, Consider SDMA or GFR Measurement<\/h3>\n
STEP 7:<\/b><\/span> Evaluate Other Systems and Less Common Causes of PU\/PD<\/h3>\n