Polyuria-Polydipsia

A precise history and consistently low urine specific gravities (<1.030) suggest pu-pd. Measurement of total water consumption (including water in food) over at least a 24-hour period is necessary to definitively verify polydipsia (normal water intake is 20 to 70 ml/kg/day). This measurement is best performed at the client’s home because some polyuric animals will not readily drink water at a clinic. Quantifying urine production is difficult unless a metabolism cage is available (normal 20 to 45 ml/kg/day).

Pu-pd has many possible causes (Table 7-1). History and physical examination are crucial in evaluating patients with pu-pd (Figure 7-1). Iatrogenic causes must be sought from the history (e.g., diuretics, glucocorticoids, anticonvulsants, high-salt or very–low-protein diets, excessive thyroid supplementation). Aminoglycosides tend to produce polyuric, acute renal failure. Glucocorticoids can cause pu-pd, even when administered rectally or topically. Pyometra is usually suggested by history (2 months post-estrus) or physical examination findings (enlarged uterus, vaginal discharge). If the clinician is unsure whether pyometra is likely, a complete blood count (CBC) and abdominal imaging are usually definitive (neutrophilic leukocytosis with left shift and enlarged uterus). Weight loss plus pu-pd in a cat suggests hyperthyroidism, renal failure, or diabetes mellitus (hyperthyroidism is rare in dogs). Enlarged thyroid glands often may be palpated in the neck in hyperthyroid patients. Feline kidneys are usually palpable; size and contour should be assessed. Postoliguric diuresis is usually diagnosed from the history (e.g., a male cat that has undergone removal of a urethral obstruction). Pu-pd is the most common presenting complaint of owners of hyperadrenal dogs; most affected dogs have a pendulous abdomen, hepatomegaly, alopecia, or a combination thereof on physical examination. Such dogs should undergo adrenal function testing (see Chapter 8). Recent onset of cataracts suggests diabetes mellitus. Peripheral lymphadenopathy suggests lymphoma causing hypercalcemia. Other neoplasms (e.g., anal sac apocrine gland adenocarcinomas) and certain infectious diseases (e.g., systemic mycoses) may also cause hypercalcemia.

TABLE 7-1 CAUSES OF POLYURIA-POLYDIPSIA (PU-PD) IN DOGS AND CATS

FIGURE 7-1 Diagnostic approach in a dog or cat with a history of polyuria-polydipsia (pu-pd); persistently hyposthenuric, isosthenuric, or inadequately concentrated urine; or a water balance study documenting water consumption greater than 70 ml/kg/day. CBC, Complete blood count; GFR, glomerular filtration rate; T₄, thyroxine; UTI, urinary tract infection.

If the cause is not obvious, a urinalysis, CBC, and biochemical profile are the next steps (see Figure 7-1). Urinary tract infections (UTIs) may be secondary to hyperadrenocorticism or diabetes mellitus, but renal infection (i.e., bacterial pyelonephritis) can cause pu-pd. Neutrophilic leukocytosis, azotemia, white blood cell (WBC) casts, renal pain, or hyposthenuria may occur with pyelonephritis. Pyelonephritis can be difficult to diagnose; excretory urography is the diagnostic method of choice (although abnormalities may also be found with ultrasonography if the renal pelvis can be imaged). Sometimes a presumptive diagnosis can only be made by the necessity for long-term antibiotic therapy after failure of short-term therapy. Clinicopathologic screening often reveals changes indicative of the cause of pu-pd (e.g., renal failure, hyperadrenocorticism, hepatic insufficiency, hypercalcemia, diabetes mellitus) (see Figure 7-1). Serum thyroxine determinations are always indicated in older cats (i.e., >10 years old).

Many dogs with hyperadrenocorticism are obviously cushingoid on physical examination (i.e., cutaneous abnormalities, potbellied appearance, and hepatomegaly). Common CBC and serum chemistry profile changes include lymphopenia, eosinopenia, and increased serum alkaline phosphatase (SAP), alanine aminotransferase (ALT), and serum cholesterol. Approximately 40% to 50% of hyperadrenal dogs have UTI. Bacteriuria is often the only abnormality on urinalysis (i.e., no hematuria or pyuria). Adrenal function tests (see Chapter 8) or hepatic biopsy may be necessary to distinguish hyperadrenocorticism from primary hepatic disease.

Renal failure, hypercalcemic nephropathy, and hypoadrenocorticism can resemble each other. The first two usually produce pu-pd, whereas the last causes it in 15% to 25% of affected dogs. Each may have azotemia, decreased renal concentrating ability (e.g., specific gravity 1.012 to 1.029), and hypercalcemia (10% to 15% of renal failure patients and 30% of hypoadrenal dogs). Most hypoadrenal patients have a serum Na : K of less than or equal to 27 : 1 with hyponatremia, hyperkalemia, or both. Classically, no stress leukogram exists despite the animal being ill. An adrenocorticotropic hormone (ACTH) stimulation test (see Chapter 8) is needed to confirm the diagnosis, because other disorders may cause similar changes. Most azotemic renal failure patients are hyperphosphatemic and only mildly hypercalcemic (i.e., <13 mg/dl), whereas most animals with hypercalcemia of nonrenal origin are normophosphatemic or mildly hypophosphatemic and may be markedly hypercalcemic. Nevertheless, distinguishing whether hypercalcemia is the cause or consequence of renal failure can be difficult if persistent hypercalcemia has produced renal damage plus hyperphosphatemia (especially when hypercalcemia is mild [11.5 to 14 mg/dl]). Such patients need a thorough search for neoplasia and require measurement of ionized calcium and parathyroid hormone (PTH) concentrations (see Chapter 8). Most dogs with hypoadrenocorticism and primary renal failure have normal to decreased ionized calcium, whereas animals with primary hypercalcemic disorders (i.e., hyperparathyroidism, hypercalcemia of malignancy) have increased ionized calcium concentrations.

More extensive testing is necessary if the diagnosis is still uncertain (see Figure 7-1). Some dogs with renal failure are polyuric because of loss of functional nephron number (may occur with 67% reduction in renal function) but maintain a sufficient glomerular filtration rate (GFR) to avoid azotemia (which requires a 75% reduction in GFR). A creatinine or iohexol clearance test is a noninvasive way to identify these patients. Water deprivation and antidiuretic hormone (ADH) response testing can be useful if the patient is not azotemic. Elimination of other causes also allows a reasonable tentative diagnosis.

Persistent hyposthenuria suggests diabetes insipidus, although hyperadrenocorticism, hepatic insufficiency, and psychogenic polydipsia are also possible. Adrenal and hepatic function testing, water deprivation and ADH response testing, or both may be indicated. Water deprivation testing should not be performed unless a CBC, urinalysis, and biochemical profile have been evaluated. Animals with metabolic causes of pu-pd can be harmed by iatrogenic dehydration.

Dysuria

Alterations in behavior associated with urination (other than polyuria) generally suggest disorders affecting the urinary bladder, urethra, or both (Figure 7-2). Irritative or inflammatory (septic or nonseptic) lesions that do not impede urine flow typically cause animals to urinate small volumes and to urinate more often, perhaps with apparent discomfort (i.e., dysuria). Urethral obstruction causes animals to make repeated voiding efforts that are either unproductive (i.e., complete obstruction) or somewhat productive but the bladder cannot be emptied (i.e., partial obstruction). Some animals with urethral obstruction have urinary incontinence. Such paradoxical incontinence occurs when accumulated urine is forced past an obstruction by markedly increased intravesicular pressure.

FIGURE 7-2 Diagnostic approach to dysuria in dogs and cats. BUN, Blood urea nitrogen; LMN, lower motor neuron; UMN, upper motor neuron; UTI, urinary tract infection; WBC, white blood cell.

Urinary obstruction must be promptly identified because uremia, hyperkalemia, and death occur within 48 to 72 hours of complete urethral obstruction, and severe structural damage occurs with chronic, partial urethral or ureteral obstruction. Urethral or trigonal obstruction typically causes an enlarged, turgid, and inexpressible bladder. Partial obstruction is more difficult to identify; however, observation of voiding plus assessment of residual urine volume in the bladder after micturition (i.e., palpation, ultrasonography, or catheterization) is usually diagnostic. Palpation per rectum of the urethra in male and female dogs and the prostate gland in male dogs is important. Mechanical obstructions, which may be intraluminal (e.g., uroliths, urethral plugs, neoplasms) or extraluminal (e.g., caused by displacement as the result of bladder entrapment in a perineal hernia, strictures, inflammation or edema of the urethra, severe prostatic diseases) are the most common. In these cases, passing a urinary catheter can be both diagnostic and therapeutic.

Even if a urinary catheter passes easily, a urethrocystogram with bladder distention should be performed when the animal cannot empty its bladder in order to eliminate anatomic obstruction (a urinary catheter can pass by an obstruction, depending on the size of the catheter, the size of the urethra, and the nature of the obstruction). Detrusor muscle dysfunction and functional urethral obstruction (i.e., detrusor-sphincter dyssynergia) are neuromuscular causes of inability to urinate. Detrusor muscle dysfunction is usually secondary to prolonged bladder overdistention secondary to urethral obstruction or neurologic diseases. Detrusor-sphincter dyssynergia is diagnosed only when anatomic causes of obstruction have been excluded. With functional obstruction, neurologic examination usually detects deficits; however, these deficits may be subtle.

Most dysuric dogs that are not experiencing obstruction have lower urinary tract inflammation, UTI being a common cause. Finding bacteriuria, often with hematuria, proteinuria, and pyuria, identifies UTI. Urine culture is the definitive test, as discussed under Bacteriuria later in this chapter. If no evidence of UTI exists or if UTI does not respond as expected to therapy, calculi, neoplasia, cyclophosphamide therapy, and rarely parasitism of the bladder should be considered.

Cats with dysuria and inappropriate urination may have UTI, especially if they are over 10 years of age. Younger dysuric cats (i.e., 2 to 6 years of age) usually have idiopathic sterile cystitis. Cats with sterile cystitis usually have hematuria with little or no pyuria. The second most common cause of these signs is urolithiasis. Idiopathic sterile cystitis typically resolves spontaneously within 7 days. If the problem does not resolve, radiography or ultrasonography of the urinary bladder or both may be needed.

If surgery is performed because of a lower urinary tract problem, the bladder and, in intact male dogs, the prostate gland should undergo biopsy regardless of how normal or neoplastic the organs appear. Bladder abnormalities may occur without gross lesions, whereas polypoid cystitis may mimic malignancy. If a urine culture is negative, cultures of bladder mucosal biopsies are also indicated.

Incontinence

Urinary incontinence is defined as the lack of voluntary control of micturition. The diagnostic approach to incontinence starts with a thorough history. The age of onset of the problem, reproductive status of the animal, relationship between the onset of incontinence and neutering, chronologic course of the incontinence, associated urinary tract problems, history of other neurologic abnormalities, whether normal micturition occurs at all, and when incontinence occurs in relation to micturition are all important, as well as any drug usage or dietary changes. Any drug or dietary change or development of a disease that stimulates a polyuria could precipitate a latent predisposition to incontinence by increasing the amount of urine the bladder must store.

A complete physical examination follows. Special attention should be paid to the bladder. Is it large and distended, small and contracted, or normal? In a male dog the prostate gland should be palpated. Anal tone and the integrity of the perineal reflex should be evaluated. Any abnormal neurologic signs should be pursued by a complete neurologic examination. Micturition should be observed and residual volume determined if there is any question about the ability of the bladder to empty. Residual volume has not been measured in large numbers of dogs and cats, but most have only a small residual volume, less than 20 ml. One must remember that some male dogs may want to repeatedly mark territory before the bladder is completely emptied. If complete micturition occurs, the empty bladder should be palpated for calculi, soft tissue masses, and wall thickness. If the bladder is not emptied, the urethra should be carefully palpated externally and per rectum in males and females. Any yellow fluid found dripping from the urethra in intact male dogs should be compared to urine since fluid from a prostatic cyst communicating with the urethra may have the same color as urine.

After the history and physical examination, the incontinence should be classified as neurogenic (associated with other neurologic problems) or not (unassociated with other neurologic signs). When the neurologic examination is abnormal, the lesion should be localized and further diagnostic tests pursued to identify the cause. Even when the neurologic examination is normal, a local neuromuscular cause (such as detrusor dysfunction) may be the cause of incontinence. Incontinence in animals with a normal neurologic examination is best approached by subdividing it into two categories on the basis of the physical examination: a distended bladder with inability to completely empty or a normal bladder with ability to void (Table 7-2).

TABLE 7-2 CAUSES OF INCONTINENCE AND DIAGNOSTIC TESTS

Color and Turbidity

Specific Gravity

Urine pH

Proteinuria

Analysis

Urine protein is usually measured with semiquantitative tests such as a urine reagent strip (i.e., dipstick) or by precipitation (i.e., sulfosalicylic acid). The dipstick is more sensitive to albumin than to globulins. Although semiquantitative test results correlate with quantitative results, semiquantitative test results should be regarded only as estimates because individual results may differ considerably from quantitative results. Spectrophotometric analysis is much more precise; it is discussed under Urine Protein : Urine Creatinine Ratio later in this chapter.

Proteinuria must be interpreted in light of urine specific gravity. Because screening tests are qualitative, more protein must be lost into diluted urine than into concentrated urine to give the same result (e.g., a trace reaction with a specific gravity of 1.010 means that more protein is being lost into the urine than with the same trace reaction with a 1.030 specific gravity).

Proteinuria associated with hyperglobulinemia due to myeloma (see Chapter 12) may be caused by Bence Jones proteins (free light chains). Bence Jones proteins do not cause a positive dipstick reaction but do cause a positive result on precipitation testing. Serum and urine protein electrophoresis are indicated in such patients, in which case most of the protein is a monoclonal spike in the β or γ regions. Such a finding necessitates a search for osteolytic or lymphoproliferative lesions. Ehrlichiosis occasionally mimics myeloma (i.e., glomerulonephritis, monoclonal-like gammopathy, bone marrow plasmacytosis). A titer may be diagnostic (see Chapter 15).

A semiquantitative test (ERD-HealthScreen; Heska Corporation—see Appendix I) is available to detect low concentrations (1 to 30 mg/dl) of albumin in urine, with separate tests for dogs and cats. This test is affected by macroscopic hematuria and by inflammation indicated by pyuria. The test is indicative of any illness, not necessarily primary renal disease, and positive results increase with age.^54–56 Repeatability problems have been reported in cats with this test, and the test did not always detect cats with urine protein : urine creatinine (UPC) ratios greater than 0.5.⁴⁰

Normal Values

A trace of proteinuria or 1+ reaction is probably normal with a specific gravity greater than 1.012 in dogs.⁵⁷ If the urine specific gravity is less than 1.012, any amount of proteinuria may be abnormal. Dipstick and sulfosalicylic acid precipitation tests had such a high level of false-positive results that a normal value was difficult to determine in cats.^39,40 The dipstick and precipitation tests are not quantitatively accurate. Quantitative tests are needed to precisely determine severity of protein loss, as discussed under Urine Protein : Urine Creatinine Ratio in the next section of this chapter.

Danger Values

None; however marked loss of albumin in urine can lead to hypoalbuminemia.

Artifacts

Urine protein may be falsely decreased on sulfosalicylic acid precipitation tests by very alkaline urine, or on dipstick tests by the presence of Bence Jones proteins. Urine protein may be falsely increased on sulfosalicylic acid precipitation tests by radiographic contrast media; and on dipstick tests by phenazopyridine, chlorhexidine, allowing the test pad to become wet during storage, allowing prolonged contact of the test pad with excessive amounts of urine, or highly alkaline urine (pH ≥ 9).

Drug Therapy That May Cause Proteinuria

Any drug that causes renal tubular or glomerular injury can cause proteinuria (Box 7-1).

Box 7-1 Selected Potentially Nephrotoxic Drugs*

Aminoglycoside antibiotics such as neomycin, kanamycin, gentamicin, amikacin, and tobramycin (important)

Amphotericin B (important)

Arsenic

Cephalothin (uncommon)

Cisplatin (important)

Cyclophosphamide (nephrotoxicity is uncommon; sterile cystitis is more common)

Dextran (low molecular weight)

Ethylene glycol (important)

Furosemide (uncommon)

Heavy metals (i.e., gold, lead, mercury)

Nonsteroidal anti-inflammatory drugs such as aspirin, ibuprofen (important when there is preexisting renal disease, hypotension or other nephrotoxic drugs)

Polymyxin B (important)

Radiographic contrast media (important when there is preexisting azotemia and dehydration)

Sulfonamides (uncommon if more soluble sulfonamides are used)

Tetracyclines (uncommon)

Thallium

Thiazides (uncommon)

Vancomycin (uncommon)

Zinc

^* Not all of these drugs reliably produce nephrotoxicity. Those drugs recognized as the most dangerous are denoted important.

Causes of Proteinuria

One must first decide if the proteinuria is significant or not by examining the specific gravity, as described earlier (Figure 7-3). If it is insignificant, one may ignore it unless the patient is receiving nephrotoxic drugs (e.g., aminoglycosides). Such drugs should be stopped regardless of the amount of proteinuria, because mild proteinuria may be an early sign of nephrotoxicity and impending acute renal failure. Aminoglycoside nephrotoxicity typically causes proteinuria or other urinalysis changes (e.g., isosthenuria, glucosuria, cylindruria) before azotemia.

FIGURE 7-3 Diagnostic approach to proteinuria in dogs and cats.

One should next determine if abnormal proteinuria could be prerenal (due to hemoglobinuria, myoglobinuria, or Bence Jones proteinuria) by examining serum globulin concentration and the occult blood results on the urinalysis.

The most common causes of abnormal proteinuria are postrenal, associated with hemorrhage or inflammation at or caudal to the renal pelvis. A urinalysis with sediment examination is performed to exclude hemorrhage and inflammation as causes. Proteinuria associated with inflammation or hemorrhage requires resolution of the inflammation or hemorrhage and then rechecking for persistence of proteinuria. The most common cause of inflammatory proteinuria is UTI. Urine culture should be performed if infection is possible. To exclude extraurinary postrenal causes of proteinuria (e.g., genital tract inflammation), a urine sample collected by cystocentesis should be examined.

If hemorrhage and inflammation are excluded by a normal (“quiet” or “inactive”) urine sediment and prerenal causes are unlikely, proteinuria is most likely of renal origin. Renal-origin proteinuria can be transient or persistent and due to glomerular or tubular dysfunction. One should measure serum albumin and repeat the urinalysis to determine if proteinuria is persistent. If hypoalbuminemia is present in association with marked proteinuria, one can assume that the proteinuria is significant and persistent. Transient (i.e., functional) proteinuria has many causes (e.g., strenuous exercise, fever, seizures, venous congestion of the kidneys) and is rarely significant. Persistent proteinuria is defined as abnormal proteinuria on at least three occasions, two or more weeks apart.³⁷ Persistent proteinuria with an inactive urine sediment should prompt determination of a UPC ratio to ascertain its severity.

Note

A normal serum albumin concentration does not mean that proteinuria is insignificant.

Urine Protein:Urine Creatinine Ratio

Indication

Measurement of the UPC ratio is indicated to determine the magnitude, and therefore the significance of proteinuria.

Advantages

Measurement of the UPC ratio is more accurate than dipstick and precipitation procedures, requires only a single random urine sample, and correlates well with 24-hour determinations. Urine samples can be collected by any method.^7,25

Disadvantages

A complete urinalysis should be performed on an aliquot of the same sample to look for macroscopic hemorrhage or inflammation, which would alter assessment of the results. In dogs with abnormal proteinuria, the UPC ratio varies day-to-day especially in the lower ranges of abnormality.⁴² This variation can be as much as 80% at values near 0.5 and 35% at values about 12 even when the same methodology is used. A single measurement will reliably estimate the UPC ratio at values less than 4, but higher values require two to five determinations. Such variation should be taken into account when following UPC ratios in dogs and cats with chronic renal diseases. The ratio gives no information about the origin of the proteinuria; it only quantifies it.

Analysis

The UPC ratio should not be determined by dipstick estimates of urine protein and urine creatinine because these are inaccurate. Urine protein and creatinine concentrations should be measured spectrophotometrically. Different assay types and equipment are used by different laboratories, and results vary by methodology, making interlaboratory UPC ratio comparisons problematic. After analysis, the following ratio is calculated: total protein (mg/dl)/creatinine (mg/dl).

Normal Values

Adult dogs and cats, less than 0.2 (higher values are normal in puppies at least up to 2 weeks of age⁴⁶ and in noncastrated male cats); borderline 0.2 to 0.5 (dogs), 0.2 to 0.4 (cats).

Danger Values

None. However, in azotemic and in hypertensive cats, the risk for death or euthanasia increases with increasing UPC ratio.^50,51 In nonazotemic, geriatric cats, the UPC ratio was predictive of survival and of development of azotemia.³³ In dogs with renal failure, a UPC value greater than 1 at initial evaluation was associated with increased risk of uremic morbidity and mortality.³² Marked loss of albumin in urine can lead to hypoalbuminemia.

Artifacts

See discussions of total protein (see Chapter 12) and of creatinine later in this chapter.

Causes of Increased UPC Ratio

Remember that inflammation and hemorrhage can increase the UPC ratio and that the UPC ratio should only be interpreted on urine with a normal urine sediment examination. In this situation, moderate proteinuria (i.e., UPC ratios of 0.5 to 2) may be associated with renal tubular or glomerular diseases.

Marked proteinuria (UPC ratio > 2) associated with a quiet sediment and normal serum globulins or a polyclonal gammopathy is usually the result of renal glomerular disease (i.e., glomerulonephritis, amyloidosis). One should search for causes of glomerulonephropathy: chronic parasitic disease such as heartworm disease, hepatozoonosis, or leishmaniasis; chronic inflammatory diseases such as systemic lupus erythematosus; chronic infectious diseases such as borreliosis, feline leukemia virus (FeLV) infection, feline immunodeficiency virus (FIV) infection, ehrlichiosis, pyometra, or endocarditis; neoplasia; endocrine diseases such as hyperadrenocorticism^31,43 and diabetes mellitus⁴⁸; and familial glomerulopathies. Immunosuppressive glucocorticoid therapy leads to mild proteinuria.^47,53 If no underlying disease is identified or if proteinuria persists despite treatment for an identified disease, renal cortical biopsy should be considered to determine whether glomerulonephritis or amyloidosis is present.

Note

Feline amyloidosis usually affects the renal medulla and may not cause proteinuria.

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

1. Microbiology and Infectious Disease
2. Neurologic Disorders
3. Leukocyte Disorders
4. The Complete Blood Count, Bone Marrow Examination, and Blood Banking: General Comments and Selected Techniques

Stay updated, free articles. Join our Telegram channel

Join