Urine, the forgotten fluid….
When it comes to laboratory submissions, one of the most frequently overlooked fluids is urine. This may be because urine can be difficult to collect if Fido just peed in the clinic flower bed prior to his appointment, or if Fluffy the cat would rather eat you than submit to a cystocentesis, but hopefully a brief overview of the potential information gained from a complete urinalysis will encourage increased collection and evaluation of this valuable material. Don’t forget the diagnostic utility of urinalysis applies to equine and bovine patients as well!
So what can a urinalysis tell us? Urinalysis can be used as a screening tool to evaluate the integrity of the urinary and other body systems. ‘Normal’ urinalysis results are valuable because they indicate that the physiologic processes governing the formation of urine (selective glomerular permeability, tubular resorption of some metabolites, and secretion of others) are functioning adequately, and may thus provide objective information to allow exclusion of the urinary system as a cause of clinical signs. The value of abnormal test results is obvious, but it should be pointed out that urinalysis may also indicate underlying disease processes earlier than serum tests - given the low renal threshold for bilirubin in most animals, bilirubinuria may be detected before hyperbilirubinemia in hemolytic and hepatobiliary disorders; mild proteinuria may be an early indicator of underlying renal disease or or hypertension.
A complete urinalysis includes determination of specific gravity, physical characteristics, chemical evaluation by reagent strip (dipstick), and sediment examination. It is important to assess all of these components as each supports the interpretation of the other, and to also consider how the sample was collected (cystocentesis vs catheterization vs free flow), as this can influence interpretation of results. Meaningful interpretation of physical urine characteristics (color, turbidity) and chemical test (protein, blood, pH, etc.) results is aided by knowledge of urine sediment results. Moderate proteinuria in the face of unremarkable urine sediment is most likely indicative of glomerular disease, whereas proteinuria accompanied by hematuria and pyuria is likely related to urinary tract inflammation or infection. Brown discoloration to urine may suggest hematuria or myoglobinuria, which would both result in a positive blood (heme) reaction on the reagent strip, but evaluation of urine sediment could be used to rule in/out hematuria, and further investigations of serum biochemistry could be utilized to determine if changes in muscle enzymes (CK, AST) are present, or if there is any evidence to support hemolysis.
Remember that reagent strip pads should not be used for specific gravity, leukocytes, or nitrites as these produce inaccurate results in domestic animals.
Knowledge of urine specific gravity (USG) by refractometry is a vital component of urinalysis and is needed for assessment of renal concentrating ability, particularly when animals are azotemic, polyuric, or oliguric. USG results should be interpreted with knowledge of the patient’s hydration status, current medications, and concurrently obtained serum biochemistry results as there are numerous disease conditions, in addition to renal disease, which can result in altered USG including diabetes mellitus, hypo- and hyperadrenocorticism, liver disease, urinary tract infections, and hypercalcemia, among others. Remember that in health USG can vary widely, depending upon hydration status.
Reagent strip analysis typically includes pH, protein, glucose, ketones, bilirubin, and blood.
pH is affected by both renal and extrarenal factors, including diet. Dogs and cats typically have a urine pH of 6.0-7.5, whereas herbivores range from 7.5-8.5. Changes in urine pH from expected ranges may indicate alterations in acid-base status, or the presence of urease-containing bacteria.
In health, there is very little protein present in urine, and most of that is albumin, which is the major protein detected by reagent stick pads. Protein results should always be evaluated in the context of the USG. Concentrated urine samples in dogs may have up to 1+ protein reactions in the absence of disease. Proteinuria in the absence of serum biochemistry changes may be an early indicator of renal disease, if post-renal conditions such as urinary tract infection are ruled out, or may help explain the cause of hypoalbuminemia noted on serum biochemistry. Alkaline urine may result in false-positive urine protein reagent stick results.
Glucose is typically all reabsorbed by the proximal tubules unless the tubular transport maximum is exceeded, which may be noted with both transient (excitement in cats) and persistent hyperglycemia (diabetes mellitus), as well as tubular disorders (Fanconi syndrome).
The reagent strip ketones pad detects primarily acetoacetate and acetone with a positive result indicating a need to search for disorders resulting in increased oxidation of fatty acids for energy (diabetes mellitus, starvation, and hypoglycemic disorders.)
The heme reagent stick pad detects heme-containing compounds (hemoglobin and myoglobin), which are not expected to be present in healthy animals. A positive result should prompt examination of the urine sediment for erythrocytes as can be found with inflammation, trauma, neoplasia, and coagulation defects. In the absence of intact erythrocytes, serum biochemistry and CBC findings should be examined to determine if hemoglobinuria or myoglobinuria are supported.
Bilirubin is not an expected finding in the urine of domestic mammals other than dogs. Concentrated urine of healthy dogs may produce a small-to-moderate positive bilirubin reaction in urine with a USG >1.040. Excessive bilirubin formation associated with hemolytic states, or impaired hepatobiliary excretion increases serum conjugated bilirubin concentrations which passes through the glomerular filter into the urine.
Examination of urine sediment allows the presence or absence of hemorrhage, inflammation, bacteriuria, cylindruria (casts in urine), crystalluria, and epithelial cells to be documented and integrated with the remainder of urinalysis findings and other laboratory data. Knowledge of expected sediment findings in health is vital to interpretation of urine sediment. In general, < 5 leukocytes and 5 erythrocytes/400X field (hpf) are expected; bacteria may be present in samples collected free flow but should not be identified in aseptically collected urine; casts may be found in limited numbers in healthy animals (typically hyaline casts), but the finding of granular or erythrocyte casts suggests renal tubular insult. Low numbers of transitional and potentially squamous epithelial cells can be found, depending upon sample collection method. Inflammation can induce cellular atypia; therefore, it is best to reassess transitional cell morphology following resolution of inflammation. Crystals can be found in healthy animals, with some species predilections such as calcium carbonate crystals in horses and low numbers of phosphate crystals in dogs and cats. Increased crystalluria may suggest the presence of certain pathologic states (e.g., infection) causing changes in either urine pH or ion concentration. The presence or absence of crystalluria is not a reliable indicator of the presence or absence of uroliths.
Hopefully this quick overview of the potential information derived from routine urinalysis has convinced you to collect a urine sample along with Fluffy’s CBC and biochemistry profile - the information is invaluable. AHL