Mysteries of Urine Dipstick Testing Revealed

Urinalysis (UA) is routinely ordered in the ER multiple times a day. At first glance it seems uber simple: Dip it in pee, give it a glance, and make a decision (the dipstick analysis). The information gained often drives treatment decisions and/or the need for further testing. Be warned though, the sensitivity and specificity of these tests is sometimes no better than rolling a dice. A deeper look reveals UA is not as simple as it seems; it’s full of subtleties and intricacies.

UA (in conjunction with other tests) is used to diagnosis various urinary tract conditions, everything from metabolic acidosis to malignancy to urinary tract infections (UTI).

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Specimen Collection: The midstream urine clean capture technique is the generally accepted standard. The old school concept of cleaning the external genitalia (particularly in women) has shown little benefit and has now all but fallen out of practice. Studies have shown specimens obtained with or without prior cleaning have near identical values (Arch Intern Med 2000;160:2537.)
*Be advised, if you can’t test the urine you’ve collected within 2 hours it needs to be refrigerated if you expect to obtain reliable data.

Gray Area: Medications, supplements, and even foods (along with dozens of other things) can cause abnormal urine odors and colours. Unremarkable urine usually looks clear to light yellow while a darker color often indicates urine concentration. Cloudy urine can be normal (caused by precipitated phosphate crystals in urine that has a PH over 7.35) but cloudy urine can also indicate significant pyuria (puss in the urine). Urine clarity (or rather absence of urine clarity) is often found in the presence of a UTI (but not always). A strong urine smell is often clinically associated with a UTI, but this can equally be the result of diet (for example after eating Asparagus). A smell of ammonia can indicate excessive bladder retention time while a fecal smell suggests GI / bladder infiltration. A red color can mean hematuria (blood in urine) but this can also be caused by eating beets, drinking beet juice, and a myriad of other causes. Brown urine can be indicative of myoglobin excretion (often seen in crushing injuries) which can often have devastating consequences to the patient’s renal system while drugs like propofol can tint it a blue hue. So basically, UA alone has a poor specificity.

False Positives and False Negatives:  The dipstick test produces many false-positives and false-negatives that can be further aggravated by inappropriate storage of urine dipsticks (these should be stored in a sealed air tight container). Treating patients on dipstick results alone is poor practice, but when you throw in outdated and improperly stored strips, the specificity and sensitivity of the results become even less reliable, sometimes no better than 50% (same as if you flipped a coin). Don’t get me wrong, dipstick testing is helpful, but if you’re making major treatment decisions based on dip stick analysis, you need to correlate your findings with microscopy and other clinical findings.

Urine Specific Gravity: Urine specific gravity (USG) generally correlates with the urine osmolality, giving you a snapshot of the patient’s hydration status. Many disease processes can cause an increase USG, such as glycosuria and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) while a decrease in USG can be indicative of diuretic use, diabetes, and a multitude of other renal complications.

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Urinary PH: When we think PH, we often think of the normal range of 7.35 to 7.45, but this normal range only refers to serum PH (like a point of care blood gas for example). A normal function of the kidney, however, is to acidify urine, which means normal urine PH ranges from 4.5 to 8. Because of normal metabolic activity, the generally accepted normal pH of urine is about 5.5 to 6.5. A patient with a finding of alkaline urine (>8) in conjunction with acidic blood serum (<7.35) can be a strong indicator of renal tubular acidosis (RTA) where the kidney cannot acidify the urine. Urine PH can also be related to something simple like diet. Acidic urine can be the result of high fruit intake that acidifies the urine while high citrate intake (found in citrus fruits, legumes, and vegetables) can alkalize urine. Carnivores can have urine that’s more acidic compared with vegetarians, which partially explains why meat eaters get more gallstones compared with vegetarians (uric acid stones form easier in acidic urine).

Hematuria:  The dipstick test for blood in urine is actually used to identify for the peroxidase activity of erythrocytes, not for actual red blood cells (RBC). So the presence of myoglobin, for example, will also produce a positive dipstick for hematuria since both myoglobin and RBC’s are a catalyst for this reaction (the product of hemolyzed RBCs or muscle breakdown both produce a positive result for hematuria). Conversely, a patient taking high dose vitamin C (even 1000+mg) will inhibit this process, meaning the test for Hematuria will be negative despite presence of blood in the urine. Remember, as high as 20% of patients presenting with gross hematuria have an underlying urinary tract malignancy, warranting a complete work-up in the presence of this finding.

Proteinuria: Healthy kidneys generally limit protein in the urine while a poorly functioning renal system will allow more protein to enter the urine. The presence of protein in urine is indicative of multiple renal disorders (healthy kidneys filter and reabsorb protein via the proximal tubule cells). Urinary proteins include primarily albumin, but some serum globulins are detected. The actual definition of proteinuria is the excretion of more than 150 mg of protein per day. Patients with early renal disease may have microalbuminuria (an increase in urine albumin). Early diabetic nephropathy may not be detected by dipstick testing, so it is not a good screening test for this condition. The dipstick test is sensitive almost entirely to albumin; it will not detect low concentrations of globulins or the Bence-Jones proteins associated with multiple myeloma.

The sensitivity of the dipstick test for proteinuria is high, but the low specificity produces false-positive results by reacting to minor proteinuria that would not be considered clinically significant. Early morning urine that’s concentrated, for example, may give a false impression of significant proteinuria. Iodinated radiocontrast agents or highly alkaline urine (as seen in renal tubular acidosis for example) will also cause a false proteinuria result.

Glycosuria: Glucose is normally filtered by the glomerulus, but this substance is then almost completely absorbed in the proximal tubule (sugar is so rare in nature, so your body is designed to keep it around). When the amount of filtered glucose, however, exceeds the kidney’s ability to reabsorb (they used to taste a PT’s urine to diagnose hyperglycemina way way back in the day), glycosuria results, making glycosuria an abnormal finding. The blood glucose is usually at least 10 mmol/L  (that’s 180 mg/dL for our American neighbors) to be detected by the dipstick.

Ketonuria: It’s super abnormal to find ketones in a patient’s urine (ketones are byproducts of fat metabolism which are almost exclusively found in uncontrolled diabetes). Some ketonuria, however, can occur normally in patients on a carbohydrate-free diet (high-protein weight loss diets), or during times of starvation or prolonged fasting (usually a person needs to fast for at least 72 hours before their body switches to ketosis)

Nitrites: Firstly, you must recognize there’s a difference between nitrates and nitrites. Although nitrates are excreted by the kidney, nitrites are not normally found in urine. When bacteria reduce urinary nitrates to nitrites, the dipstick will identify this condition. One needs the presence of bacteria for the dipstick to register a positive nitrite. Therefore a  positive nitrite test usually means infection (since you need that bacteria to create nitrites our of nitrates). One usually needs more than 10,000 bacteria per ml to turn the dipstick positive, making it a test with high specificity but low sensitivity. In other words, a negative nitrite test does not rule out a UTI, but a positive one strongly suggests infection. Of course, and infection with non-nitrate-reducing organisms (organisms that do not convert nitrates to nitrites) will result in a negative nitrite test. Also, if a patient’s diet is deficient in nitrates, the test will be falsely negative in the presence of infection since there are no nitrates for the bacteria to convert in nitrites. Since the nitrite panel on the dipstick is highly sensitive to ambient air, improperly stored dipsticks are the most common cause of a false-positive test for nitrites.

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Leukocyte Esterase: LE is an enzyme produced by neutrophils (one of the first cells that travel to the site of an infection). It may signal pyuria (puss in the urine) which is often associated with UTI. Although the sensitivity of the LE test is high, the specificity is low. WBCs anywhere in the GU tract, including the vaginal vault, will produce a positive LE panel. When evaluating for Leukocyte Esterase the dipstick should be allowed to sit for at least 30 to 60 seconds before reading the LE test. The non-specificity of LE testing causes false positives in patients with chlamydia infections, urethritis, tuberculosis, bladder tumors, viral infections, nephrolithiasis, foreign bodies, and corticosteroid use.

Bilirubin and urobilinogen: Urine does not usually contain bilirubin, the presence of which is often an indicator of hepatic disease. Any bilirubin found in the urine is conjugated bilirubin because unconjugated bilirubin cannot pass through the glomerulus. Biliary obstruction or liver disease will cause an elevated urine bilirubin. While there can be small amounts of urobilinogen in the urine, Urobilinogen is the end-product of conjugated bilirubin after it passes through the bile duct and has been metabolized in the intestines. This urobilinogen is reabsorbed into the portal circulation and eventually filtered by the kidney. Patients with hemolysis or other types of liver disease will have an elevated urobilinogen level. If the bile duct is obstructed, less bilirubin enters the intestine, and therefore less urobilinogen is detected in the urine.

So what’s the synopsis? Urine dipstick testing is a valuable tool for the clinician, but it’s limitations must be understood, with both false positives and false negatives commonplace. Understanding the specifics of each test and following to confirm or deny results is essential when painting a clinical picture. Don’t tunnel vision, question the validity of your results, and always remember to treat the patient, not the dipstick.

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