A colleague at the University of California always says, "If an animal is sick enough to get blood, it are sick enough to get urine." Indeed, urinalysis is one of the most economical yet the most useful tests for evaluating a canine or feline patient. In this presentation, I will review the indications for a urinalysis and urine sediment examination, the components of a urinalysis, factors that may affect test results, and interpretation of urine sediment findings.

Indications for Urinalysis

Urinalysis is a baseline laboratory test, along with a CBC and chemistry panel. A urinalysis is especially indicated in the assessment of systemic disorders, such as metabolic or endocrine disease, and in the evaluation of renal and urinary tract disease. Urinalysis is cost-effective and easy to perform in your clinic. Urinalysis includes physical, chemical, and sediment evaluations.

Urine Collection and Sample Management

Collection method may impact microscopic (and bacteriologic) findings and interpretation. For example, cystocentesis samples may contain RBCs, catheterized samples may contain lubricant gel and epithelial cells, and voided samples may contain debris and epithelial cells and may be contaminated with bacteria. Always record the method of urine collection so the results can be interpreted accurately. A concentrated sample (first urine in the morning) is best.

Urine is unstable and must be analyzed promptly! It should be collected in clean or sterile containers and if not analyzed within a short period of time (e.g., an hour or two), it should be refrigerated. Cold urine should be allowed to return to room temperature prior to analysis to avoid a false increase in specific gravity. Precipitates may form in urine as it cools, and cold may interfere with some chemical tests. Urine collected for some biochemical tests (e.g., electrolytes) may be frozen. If mailing specimens, check first with the laboratory to check on recommended preservatives. Effects of delayed analysis include bacterial overgrowth, increased pH, formation or dissolution of crystals, breakdown of casts, lysis of erythrocytes, and breakdown of bilirubin.

Physical Evaluation of Urine

Urine volume depends on hydration status and renal concentrating ability; it is inversely related to the specific gravity

Urine color is normally yellow to amber due to the presence of urochromes (i.e., urobilin and other degradation products of hemoglobin). Urine concentration will affect the depth of the color. Cloudy red urine that clears after centrifugation is seen when RBCs (hematuria) are present. Dark red to brown color may be due to hemoglobinuria or myoglobinuria; iron oxidizes (turns brown) with time. Yellow-brown, greenish-yellow, or dark brown urine may be due to bilirubinuria; bilirubinuria also causes yellow-green foam to form when the urine is shaken. Pink, blue, or other urine colors may result from some drug therapy.

Urine transparency (turbidity). Urine normally is clear. Semen, mucus, and lipid may cause turbidity in normal urine. Increased numbers of cells, crystals, casts, or organisms can increase the turbidity of urine in disease conditions.

Urine odor. Putrid or ammonia odors may indicate sepsis. An acetone odor may be noted in urine from animals with ketosis/ ketoacidosis.

Urine specific gravity is one of the most important tests in a urinalysis and should be done using refractometry (dipstick tests for specific gravity are highly inaccurate). Turbidity of the urine can artifactually affect the specific gravity (usually increase it), so urine should first be centrifuged and the supernatant used for determination of specific gravity. Normal specific gravity values vary widely (usually between 1.015 and 1.045, up to 1.065+ in cats) depending on hydration status and water intake. Cat urine contains different solutes than dog urine; therefore, some refractometers have separate scales for cat urine to adjust for this. Specific gravity must be evaluated in light of BUN/creatinine values and hydration status. Abnormal substances such as glucose and proteins may falsely increase the specific gravity.

Chemical Evaluation of Urine (Dipstick Analysis)

Dipsticks are labile. They must be kept dry, in well-capped jars, and used prior to the expiration date for accurate results. Prolonged exposure to air may cause false positive tests for glucose and false negative tests for occult blood (hemoprotein).

Urine pH. Acidic urine is caused by increased acid excretion or production (increased protein catabolism, [high protein diet, fever, starvation, nursing], metabolic or respiratory acidosis, paradoxical aciduria with alkalosis). Alkaline urine is caused by increased alkali excretion or production (decreased protein catabolism [e.g., low protein diet], cystitis due to urea-splitting bacteria, prolonged storage at room temperature, metabolic or respiratory alkalosis). Urine pH is not an accurate indicator of systemic acid/base balance.

Protein. Urine protein results always must be interpreted in conjunction with specific gravity. A small amount of protein normally is present in urine and may be detected in concentrated urine. Many false positive protein tests occur, especially with alkaline urine. The protein test detects mainly albumin. Physiologic (prerenal) proteinuria may result from excessive muscular exertion, convulsions, or excess protein ingestion. Pathologic proteinuria may be prerenal (hemoglobinuria, myoglobinuria), renal (glomerular or tubular), or postrenal (urogenital hemorrhage or inflammation). A sulfosalicylic acid precipitation test may be done to confirm the presence of proteinuria. This test is more sensitive and specific than the dipstick test.

Glucose. Glucose is not normally found in urine. Glucosuria occurs when blood glucose levels exceed the renal threshold for reabsorption (>180 mg/dl in dogs, 280 mg/dl in cats). Glucosuria with hyperglycemia occurs in diabetes mellitus, with dextrose administration, or secondary to catecholamines or glucocorticoids. Glucosuria without hyperglycemia may occur when hyperglycemia is transient or in selective renal proximal tubule dysfunction. Urine containing glucose is an excellent culture medium for bacteria!

Ketones. Ketonuria occurs when ketone production exceeds the renal tubular absorption capacity. The urine ketone test detects acetoacetate and some acetone, but not beta hydroxybutyrate. Ketonuria may occur in diabetes mellitus, pregnancy, ketosis, or starvation.

Hemoprotein (occult blood). Hemoproteinuria may result from increased RBCs (hematuria, especially when the urine is dilute such that the RBCs lyse), hemoglobinuria, or myoglobinuria. The sediment should be evaluated for RBCs to help differentiate hematuria from hemoglobinuria and myoglobinuria. Typically, red urine supernatant indicates hemoglobin or myoglobin. Also, hemoglobinuria usually is accompanied by hemoglobinemia, so the serum color should be checked. More specific biochemical tests may be needed to differentiate hemoglobin from myoglobin.

Bilirubin. Only conjugated bilirubin is water soluble and excreted in urine. Bilirubin breaks down when exposed to light. Dogs with concentrated urine may have trace to 1+ bilirubinuria; they have a lower renal threshold for bilirubin than do other species, and canine renal epithelium also can conjugate and excrete bilirubin (especially in male dogs). The Ictotest is more accurate than the dipstick test.

Urobilinogen is a breakdown product of bilirubin, formed by bacteria in the gut. This test is highly inaccurate (low sensitivity, many false negative results) and should not be used in dogs and cats. Other urine dipstick tests that do not work reliably in animals include the nitrite test and the leukocyte esterase test.

Evaluation of Urine Sediment

Microscopic evaluation of urine sediment is done both at low power (X10 objective, lpf) and high power (X40 objective, hpf). "Normal" urine sediment contains less than 5 RBC/hpf (seen often in cystocentesis samples) and 5 WBC/hpf, (seen often in voided samples). Voided samples also may contain squamous epithelial cells. A low number of transitional epithelial cells or sperm is normal, as are rare hyaline or granular casts. Crystals also may be found normally, depending on urine pH, species, and diet. Calcium oxalate crystals are found in acidic urine, whereas, triple phosphate, amorphous phosphates, and struvite crystals are found in alkaline urine. Fat droplets often are found, especially in cat urine, and have no known significance.

Hematuria is defined as > 15 RBCs/hpf. Additional investigation must be done to determine the source of the hematuria (renal or postrenal).

Pyuria is defined as > 10 WBCs/hpf. Additional investigation must be done to determine the source of the pyuria (renal or postrenal).

Casts. More than 2 casts/lpf are considered significant. Hyaline casts are proteinaceous and may be observed normally, with proteinuria or with mild renal disease. Cellular casts always are abnormal. RBC casts may occur with hemorrhage, WBC casts may occur with nephritis, and renal tubular cell casts occur with necrosis and sloughing of renal tubules. Granular casts are composed of degenerated cells and protein and usually indicate renal tubular necrosis. Waxy casts are probably desiccated granular casts and suggest advanced, chronic renal disease.

Crystals. Abnormal crystals include calcium oxalate monohydrate (ethylene glycol toxicity), ammonium biurate (hepatic disease), cystine (hereditary tubular disease), tyrosine (hepatic disease), leucine (hepatic disease), bilirubin (with bilirubinuria), and drug crystals (e.g., sulfas).

Cells. Abnormal cells include renal tubular cells, caudate epithelial cells (from the renal pelvis), increased numbers of transitional epithelial cells, neoplastic cells, and inflammatory cells.

Organisms. Bacteria, yeast, fungi, and parasite ova may be found in urine.

Biochemical Tests on Urine

Urine osmolality requires an osmometer and is a sensitive way of measuring urine concentration. Osmolality is a measure of the number of dissolved solutes/particles in a fluid.

Urine protein: creatinine (P:C) ratio is useful for determining the magnitude and significance of proteinuria. Total protein (microprotein) and creatinine should be determined on the same urine sample. A ratio >1.0 is indicative of significant protein loss in dogs and cats; the magnitude of increase may help differentiate glomerular from tubular disease. Inflammation and hemorrhage may invalidate results, but usually only when grossly abnormal.

Urine electrolytes may be useful for evaluating renal disease, dietary intake, pharmacologic effects, and fluid therapy. Absolute values are quite variable with species, diet, and water intake (urine concentration). The fractional excretion of electrolytes (Na⁺, K⁺, Ca⁺⁺, PO4, Cl^-) may be more useful. Fractional excretion provides a meaningful estimate of urine electrolyte loss. Results are affected by variability in intake and non-renal excretion of electrolytes, limiting the usefulness of the calculation:

Urine creatinine determination is needed to calculate fractional electrolyte excretion, creatinine clearance, and P:C ratio.

Tumor marker test is available for the detection of transitional cell carcinoma antigens. This test has high sensitivity but low specificity. Limitations of the test include false positive results caused by hematuria, pyuria, and severe proteinuria.