A major challenge to providing diagnostic laboratory services in resource-limited settings, like the refugee camps discussed in last month’s post, is lack of infrastructure. Without running water, electricity, and even access to good phlebotomy supplies, specimen collection and preparation can be difficult, let alone the actual testing. I’ve found that in many instances, going back to the basics can often help determine a means of providing useful laboratory results. This post focuses on the humble, yet powerful, urine dipstick.
The urine dipstick is lightweight, easily portable, requires no special handling or storage and most have long shelf lives. These characteristics make the dipstick a great tool for use in the field. The specimen–simply urine–is also easy to collect and requires no special preparation. Dipstick testing can serve as a screening tool for some diseases and a diagnostic test for others. Urine dipstick measures pH, specific gravity, nitrites, leukocyte esterase, peroxidase activity, glucose, ketone, bilirubin, protein, and urobilinogen all performed within about a minute.
Urine is slightly acidic fluid and its pH is maintained essentially by the kidney. Any acid-base imbalance affects urinary pH. Urinary pH levels are helpful in the evaluation of nephrolithiasis, infection, and renal tubular acidosis. Kidney’s ability to concentrate urine is readily assessed by measuring the specific gravity of urine and the measurement generally correlates with urine osmolality.
Both nitrites and leukocyte esterase are used to evaluate urinary tract infection (UTI). A specific group of bacteria with reductase enzyme reduces nutritional nitrates in urine to nitrites which is detectable by urine dipstick testing. Some bacteria are not capable of converting nitrates to nitrites and therefore patients with UTI could still be negative for nitrite. Patients on a nitrate-deficient diet could be negative for nitrite despite the presence of bacteria with reductase enzyme in urine. In addition, the conversion of nitrate to nitrite requires time as well as at least 10,000 bacteria in milliliter of urine for the chemical reaction on the pad to occur. Thus, first morning urine is a specimen of choice for nitrite test. Outdated dipstick or a dipstick exposed to air could also cause a false positive reaction for nitrite. In the context of these limitations, nitrite test is only specific (92-100%) for bacteria capable of converting nitrate to nitrates and has very poor sensitivity (19-48%).
Leukocyte esterase is an enzyme produced by neutrophils. This enzyme is released from lysed neutrophils. The presence of esterase enzyme in the urine may imply UTI. However, white blood cells could present in the urine secondary to bacterial and viral infections, or because of other conditions such as tumor in the bladder. Unlike nitrite, leukocyte esterase is somewhat sensitive (72-97%) but not as specific (41-86%).
The presence of glucose or ketone in the urine is not normal. Glucose is detected in the urine when the blood glucose level is greater or equal to 180 mg/dL. In this level of glucose in blood, the kidney readily overwhelms its ability to re-absorb by filtering excess glucose. The presence of ketone in urine is suggestive of poorly managed blood glucose level, starvation, and prolonged fasting. When used combined, both measurements can be used to identify and monitor diabetic patients.
Detectable protein (only detects albumin, not other proteins) in urine is indicative of renal disease. The normal protein level in urine is less than 150 mg/dL and is below the threshold a urine dipstick can detect. Significant proteinuria with 96% sensitivity and 87% specificity is detected when urine protein level exceeds 300 mg/dL. Because of its insensitivity to microalbuminuria, dipstick test has limited clinical utility in screening diabetic patients.
Urine dipstick is used to identify the peroxidase activity of red blood cells, not for the presence of intact erythrocytes. Therefore, urine dipstick alone cannot be used to diagnose hematuria unless combined with microscopy finding. Hematuria is defined by American Urological Association the presence of at least 3 red blood cells per high power field. Positive peroxidase activity in the absence of red blood cells under microscope could mean myoglobinuria (e.g. caused by rhabdomyolysis), hemoglobinuria (e.g. caused by hemolytic condition and infections), or false positives. False-positives could arise from urine contamination with oxidizing agents, semen in the urine, blood contamination from hemorrhoids or vaginal bleeding, or from foods and medications such as beets, hydroxocobalamin, and phenazopyridine.
The presence of detectable conjugated bilirubin and/or urobilinogen is suggestive of liver disease, in vivo hemolysis, and/or biliary obstruction. Low concentration of urobilinogen in urine is normal. Bilirubin is converted to urobilinogen by bacteria in the intestine.
The chemical analysis of urine provides valuable information about the function of multiple organs or systems within a very short analytical time. If the limitations and inferences of the chemical reactions are properly addressed during interpretation, the diagnostic utility of urine chemical test is high. In situations where access to laboratory testing is low, the dipstick can provide clues to aid diagnosis.
-Merih Tewelde, PhD, contributed to this post.
–Sarah Riley, PhD, DABCC, is an Assistant Professor of Pediatrics and Pathology and Immunology at Washington University in St. Louis School of Medicine. She is passionate about bringing the lab out of the basement and into the forefront of global health.