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Urine Dipstick Testing: Everything You Need to Know

BY JAMES R. ROBERTS, MD The latter function is disrupted in a variety of diseases. hink of all the times you order The normal USG ranges from Turinalysis each shift. It seems 1.003 to 1.030. USG less than 1.010 to be a straightforward test, and is suggestive of relative hydration, most physicians think they are and values greater than 1.020 in- well versed in the interpretation dicate relative . Patho- of the results: You give it a glance logic conditions that increase the and make a decision. The dipstick USG without regard to hydration analysis, the microscopic exam, included and syndrome and other information gleaned of inappropriate antidiuretic from a UA make their way into ­hormone secretion (SIADH). decision-making for a variety of ­Osmolality is the more important diagnostic, therapeutic, and dis- parameter to measure in such position issues. Like most things cases. A decreased USG, also learned in detail many years known as dilute , is associated ago, the interpretation of the UA with use, insip- should be revisited on a regular idus, adrenal insufficiency, aldoster- basis. onism, or a plethora of conditions I find myself thinking I know James R. Roberts, MD causing impaired renal function. Clear urine with a dipstick strongly positive for blood usually means everything about a certain test It should be noted that the . In such cases, the microscopic analysis would be negative only to find that the guidelines for RBCs. Significant myoglobinuria can produce acute renal failure. ­purpose of the is to concen- have changed, technology has ad- trate urine when needed. Many vanced, and previously held dogma honored ritual of cleaning the ex- . Certain foods such as as- renal diseases alter this concentrat- is now relegated to the status of ternal genitalia in women has little paragus or beets and a variety of ing function and result in a fixed misconception. When one con- or no proven benefit, although it is medications can change the odor specific gravity — about 1.010, the siders the complexity of the UA, it commonly emphasized. Some re- or color of urine. colors specific gravity of the glomerular is obvious that this is not a simple views put the contamination rates the urine brown, carrots can pro- filtrate. This is known as isosthen- test. The intricacies and subtleties as similar in specimens obtained duce a deep yellow color, and uria, a condition seen, for example, are actually quite amazing. This with or without prior cleaning. pseudomonas , propofol, in patients with renal dysfunction month’s column focuses on dip- (Arch Intern Med 2000;160[16]: and amitriptyline may give a blue/ because of . stick testing, and next month’s will 2537.) Urine should be refrigerated green hue to the urine. Urinary pH: The urine pH gener- review urine microscopy. if it cannot be examined for more Dipstick Analysis: The accuracy ally reflects the pH, but the than two hours because delayed of detecting microscopic , primary and normal function of the kidney is to acidify the urine. Nor- Urinalysis: A Comprehensive analysis can produce unreliable significant , or urinary Review results. tract is a subject of much mal serum pH is 7.4, but the normal Simerville J, Maxted WC, Physical Properties: A variety interest and practicality to emer- urinary pH ranges from 4.5 to 8. Pahira JJ of foods, medications, metabolic gency physicians. The urine dipstick Because of normal metabolic activ- Am Fam Physician products, and infections can cause has false-positive and false-negative ity, the generally accepted normal 2006;74(7):1096 abnormal urine colors and odors. results, and a list is presented in the pH of urine is about 5.5 to 6.5. The Normal urine is clear and light yel- table. It also should be noted that kidney cannot acidify the urine in The authors of this nifty review dis- low in color. Concentrated urine the commonly used urine dipstick (RTA), so cuss the value of the standard UA produces a darker color, a common has a finite lifespan, should be kept the urine can be alkaline while the for diagnosing many urinary tract finding in the morning after in a closed container, and should patient’s serum demonstrates a conditions, including malignancy overnight water restriction. Cloudy not be constantly exposed to air. metabolic acidosis. and metabolic issues. The review urine can be normal, usually Testing with outdated and improp- The urine pH can be related to covers the correct method for per- caused by precipitated phosphate erly stored materials can lead to er- diet. Acid urine can be the result forming urinalysis and highlights crystals in alkaline urine. Significant roneous results. Dipstick testing is of ingesting fruits (hence the use the importance and diagnostic also can cause clouded quite helpful, serving as a screening of cranberry juice) that acidify the value of a number of abnormal res- urine. test for some conditions and a urine. Diets high in citrate and in ults found on the dipstick and with Urine clarity is a good but not definitive test for others. Dipstick citrus fruits, legumes, and veget- microscopy. Information gained for infallible guide to the presence or testing in complicated cases or seri- ables can cause alkaline urine. Meat the UA is termed invaluable by absence of UTI. (Pediatrics 2000; ous disease must be correlated with eaters tend to have more acidic these urologists from Georgetown 106[5]:E60.) Many believe that microscopy and clinical parameters. urine, and vegetarians tend to have University. odoriferous urine is a sign of infec- : Urine alkaline urine. Alkaline urine in the Specimen Collection: A mid- tion, but it can simply represent a specific gravity (USG) generally presence of a documented UTI stream clean-catch technique is concentrated specimen or a partic- correlates with the . may suggest infection with a ur- usually adequate for most men and ular diet. Urine that has prolonged The most useful information de- ea-splitting organism (such as pro- women and in most ED situations. bladder retention time can develop rived from the USG is insight into teus). Triple phosphate crystals These authors say (and many an ammonia-like odor. A fecal smell the patient’s hydration status and (magnesium ammonium phosphate would disagree) that the time- in the urine suggests a GI-bladder the concentrating ability of ­kidneys. crystals) in alkaline urine can form

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a staghorn calculus. Uric acid concentration to the required Iodinated radiocontrast agents stones form in an acidic urine. cutoff deemed positive, 3 plus or and a highly alkaline urine may Hematuria: The strict definition more on the dipstick. The authors turn the dipstick falsely positive. of hematuria by the American Uro- note that up to 20 percent of pa- Glycosuria: is nor- logical Association is the presence tients with a gross hematuria have mally filtered by the glomer- of three or more red cells per high- a urinary tract malignancy, so this ulus, but this substance is then powered field in two of three urine condition requires a full workup. almost completely absorbed in samples. The urine dipstick is used Hematuria, in the absence of pro- the . Glycosuria to test for the peroxidase activity teinuria or RBC casts, suggests a results when the amount of of erythrocytes, not for the actual pure urologic cause (stones/ filtered glucose exceeds the presence of the physical RBC. Of malignancy) for hematuria. kidney’s ability to resorb, mak- course, myoglobin and Proteinuria: Healthy kidneys ing glycosuria an abnormal produce a positive dipstick for limit the permeability of finding. The blood glucose is hematuria because these sub- the glomerular , but dis- usually at least 180 mg/dL to stances also will catalyze this reac- eased kidneys allow more protein be detected by the dipstick. tion; these are the end-products of to be filtered so proteinuria is a : It is not normal hemolyzed RBCs or muscle break- hallmark of a variety of renal dis- to find ketones in the urine. down. High doses of vitamin C will eases. Blood are normally Ketones are the product of inhibit this process, and can inval- filtered and then reabsorbed by metabolism that is commonly James R. Roberts, MD The eyeball analysis of dipsticks has idate the dipstick for this test. This the proximal tubule cells. Urinary encountered in uncontrolled been replaced with machine reading. also holds true for stool guaiac proteins include primarily , diabetes. Some ketonuria can This device reads the dipstick and testing; vitamin C can produce a but some serum are de- occur normally in patients on a transfers the results directly to an false-negative occult blood in tected. The actual definition of pro- -free diet electronic medical record. stool. It has always been standard teinuria is the excretion of more (high-protein weight loss diets) that a positive dipstick for blood in than 150 mg of protein per day. and occasionally with or ­reagent on the dipstick is quite the absence of RBCs by micro- ­Patients with early renal disease a prolonged fast. sensitive to environmental air, so scopy is indicative of myoglobin- may have . Early Nitrites: There is a difference this test is the one that is most uria or , not true may not be between nitrates and nitrites. ­affected when out-of-date dipsticks hematuria. detected by dipstick testing, so it ­Although nitrates are excreted by or those kept in an open container The authors present a table list- is not a good screening test for the kidney, nitrites are not normally are used. Improperly stored dip- ing 45 causes of hematuria; some this condition. The dipstick test is found in urine. The dipstick will sticks are the most common cause rare ones, such as Fabry’s disease, sensitive almost entirely to albumin; identify this condition when bac- of a false-­positive test for nitrites. will likely escape the detection and it will not detect low concentrations teria reduce urinary nitrates to ni- : LE is an en- knowledge of the emergency phys- of globulins or the Bence-Jones trites. One needs the presence of zyme produced by neutrophils. It ician, but it is important to know proteins associated with multiple for the dipstick to register may signal pyuria associated with that hematuria can be associated myeloma. a positive nitrite. UTI. WBCs anywhere in the genit- with malignant , The dipstick is actually quite A positive nitrite test usually ourinary tract, including the vaginal ­numerous urinary tract , sensitive for proteinuria, and pro- means infection. It generally re- vault, will produce LE. The dipstick ­infections, nephrolithiasis, duces false-positive results by quires more than 10,000 bacteria should be allowed to sit for at least () and , tubercu- ­reacting to minor proteinuria that per ml to turn the dipstick positive, 30 to 60 seconds before reading losis, and a variety of drugs, in- would not be considered clinically making it a specific but not a very the LE test. LE is somewhat non- cluding the obvious — heparin and significant. Concentrated early sensitive test. A negative nitrite specific, and will be positive in warfarin. morning urine may give the false test does not rule out a UTI, but a ­patients with chlamydia infections, RBC casts are classic for acute impression of significant proteinuria. ­positive one strongly suggests in- , , bladder . Hematuria also The authors state that the dipstick fection. Infection with non-nitrate-­ ­tumors, viral infections, nephrolithi- can be associated with TTP, renal must be 3 plus or greater for pro- reducing organisms will result in a asis, foreign bodies, and corticost- vein thrombosis, , or tein to be considered significant. negative nitrite test. If the diet is eroid use. merely running a marathon. Contrary ­Interestingly, prolonged standing deficient in nitrates, the test may and urobilinogen: Urine to popular belief, significant hem- can produce proteinuria, termed also be falsely negative in the does not usually contain bilirubin. aturia will not elevate the protein ­orthostatic (postural) proteinuria. ­presence of infection. The nitrite Any bilirubin found in the urine is conjugated bilirubin because un- conjugated bilirubin cannot pass Accuracy of Urinalysis for Disease Detection through the . Biliary ob- struction or disease will cause Condition Test Results Sensitivity (%) Specificity (%) an elevated urine bilirubin. There Microscopic hematuria Dipstick ≥ 1 + blood 91-100 65-99 can normally be small amounts of Significant* proteinuria Dipstick ≥ 3 + protein 96 87 urobilinogen in the urine. Urobilino- Culture-confirmed UTI Dipstick n Abnormal leukocyte gen is the end-product of conjug- 72-97 41-86 esterase ated bilirubin after it passes through n Abnormal nitrites 19-48 92-100 the bile duct and has been metabol- Microscopy n >5 WBC/HPF 90-96 47-50 ized in the intestines. This urobilino- n >5 RBC/HPF 18-44 88-89 gen is reabsorbed into the portal circulation and eventually filtered by n Bacteria (any 46-58 89-94 the kidney. Patients with amount) or other types of liver disease will * Defined as 3 + or greater on dipstick. have an elevated urobilinogen level. Source: Adapted from Am Fam Physician 2006;74(7):1096. Continued on next page

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such bizarre things such as IG is common with endocarditis and I frequently encounter trace to Urine Testing nephropathy and Goodpasture’s aortic dissection. 1 plus protein via dipstick testing. Continued from previous page disease. No normal individual can The dipstick for blood is prob- It is rarely important in the ED. possibly remember all these condi- ably the test result of greatest util- Trying to track down trace or 1 If the bile duct is obstructed, less tions during a busy shift. ity to the EP, but this is a very plus proteinuria is a useless task bilirubin enters the intestine, and Trace-positive dipsticks often sensitive test that has a number of in the ED and probably in general therefore less urobilinogen is detec- confuse the clinician, and those false-positives. The few RBCs that practice. Unlike the dipstick ted in the urine. done in the ED don’t always match normally inhabit the urine (2–3) that detects albumin, the sulfos- Comment: This article is hum- the lab tech’s report. There is no can give a trace reading. alicylic acid test (SSA) detects all bling, and makes the clinician yearn totally agreed-upon standard The dipstick does not identify proteins in the urine. The SSA for the memory and recall prowess about how to use the dipstick in RBCs; it essentially detects the test would pick up a myeloma he had in medical school. One mar- the ED. Most clinicians use the dip- presence of RBC peroxidase activ- kidney (Bence-Jones light chain vels at how the interpretation of stick to screen for problems, and ity, whether these cells are intact, immunoglobulins). the lowly UA dipstick has morphed eschew sending the UA to the lab or if there is merely free hemo- With regard to specific gravity, into a very sophisticated science. for repeat testing or microscopy if globin in the specimen. Even if the one reason sickle cell patients The main take-home point from the dipstick is totally negative. This patient is on heparin or warfarin, often go into crisis when there is this discussion is that dipstick test- seems reasonable. (Clin Nephr gross hematuria has always promp- no good reason to be dehydrated ing is not an exact science. 1994;41[3]:167.) Positive findings ted a consideration for malignancy. is that they cannot concentrate Physicians may think that they may or may not prompt the lab to This is similar to finding occult their urine. Finding a USG of 1.010 are well versed in the interpretation perform the same or additional blood in a stool sample in a patient in a patient with advanced sickle of a dipstick urinalysis, but a peri- studies. When serious pathology is on iron or aspirin. It may well be cell disease does not mean they odic review is helpful. It might not suspected, however, one usually related to the drug, but you just are well hydrated. They may be be a bad idea to carry this article combines dipstick testing with mi- can’t say for sure. Dehydration and quite dehydrated and unable to in your briefcase because the in- croscopy and clinical information. exercise will give a false-positive concentrate their urine. USG usu- formation is difficult to find in gen- Kidney stones, for example, can be dipstick for true hematuria, and vit- ally corresponds to osmolality, but eral textbooks. I particularly liked associated with a 10 percent to 20 amin C (blocks peroxidase activ- large molecules in the urine, such the tables (45 causes of hematuria percent incidence of a negative ity), use, a pH less than as glucose or IV dye, can produce and 37 causes of proteinuria), dipstick for blood. Don’t rule out a 5.1, and proteinuria may produce a large changes in USG with relat- which widen one’s differential from kidney stone solely on the basis of false-negative dipstick analysis for ively minimal changes in osmolality. just a kidney stone and to a negative dipstick. And hematuria blood. It has been shown that there is no clear or consistent relationship between USG and osmolality so an Urine Dipstick Testing: osmometer should be used when Causes of False-Positive and False-Negative Results osmolality determinations are im- portant. (Arch Dis Child 2001;85 Dipstick test False-positive test False-negative test [2]:155.) Bilirubin (Pyridium) Chlorpromazine (Thorazine), selenium With regard to urinary pH Blood1 Dehydration, exercise, hemoglobinuria, Captopril (Capoten), elevated specific ­(normal 4.5–8.0), there are many menstrual blood, myoglobinuria, semen gravity, pH <5.1, proteinuria, causes of alkaline urine, and not all in urine, highly alkaline urine, oxidizing vitamin C, dipstick exposed to air patients with this finding have ur- agents uses to clean perineum ea-splitting organisms. The kidney’s Glucose Ketones, levodopa (Larodopa), dipstick Elevated specific gravity, uric acid, task is to acidify urine, and nor- exposed to air vitamin C mally a serum pH of 7.4 produces a Ketones Acidic urine, elevated specific gravity, Delay in examination of urine urine pH of about 6.0. Interestingly, some drug metabolites (e.g., levodopa) in the presence of urinary tract Leukocyte Contamination,2 nephrolithiasis Elevated specific gravity, glycosuria, obstruction­ by a stone, the kidney esterase3 ketonuria, proteinuria, cephalexin (Keflex), loses its ability to secrete acid, nitrofurantoin (Furadantin), tetracycline, and obstruction alone can produce , vitamin C alkaline urine. (Pediatr Nephrol Nitrites Contamination, exposure of dipstick Elevated specific gravity, elevated 1988;2[1]:34.) Patients with a signi- to air urobilinogen levels, nitrate reductase- ficant metabolic acidosis would be negative bacteria, pH <6.0, vitamin C expected to produce an acidic 4 Protein Alkaline or concentrated urine, Acidic or dilute urine, primary protein urine, usually below 5.0. Higher pH quaternary ammonia compounds, is not albumin, such as Bence-Jones would suggest RTA. iodinated radiocontrast agents protein In my experience, finding a trace 5 Specific gravity Dextran solutions, IV radiopaque dyes, Alkaline urine or 1 plus leukocyte esterase (LE) is proteinuria commonly a falsely abnormal test. Urobilinogen Elevated nitrate levels, phenazopyridine This is likely mostly because of contamination. Interestingly, neph- 1. Test depends on peroxidase activity of RBC. Tests will be positive with intact or lysed cells. This test is very sensitive and may be positive in normal urine (1-2 RBC/HPF). rolithiasis alone, in the absence of 2. Especially vaginal contamination. infection, can produce a dipstick positive for LE. This may lead the 3. Sterile pyuria seen with interstitual nephritis, TB, and nephrolithiasis. clinician to suspect infection in 4. Not clinically significant unless 3 + or greater. Detects mainly albumin and requires protein excretions of 300-500 mg/day. the stone former when it is not 5. Accurate analysis for osmolality requires osmometer. present. With regard to the ability of the dipstick to diagnose UTI Adapted from Am Fam Physician 2006;74(7):1096. (confirmed by culture), the

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­specificity for a positive LE test a gold standard for many things. can be as low as 41 percent. A plethora of conditions produce Many organisms are capable of false-positive or false-negative converting nitrates and nitrites, but results. It can serve as a useful non-nitrate-reducing organisms guide to the emergency physician also can cause false-negative ni- as a screening test or as a dia- trite results. Of course, patients gnostic test, but there are times who consume a low-nitrate diet will when the dipstick must be correl- not have the nitrate substrate for ated with other testing and clinical the bacteria to convert. information. EMN The nitrite test is much more sensitive for infection than the LE, Share this article on Twitter although it takes a while for the and Facebook. bacteria to reduct the nitrates to Access the links in EMN by nitrites. The urine must remain in reading this on our website or in the bladder for some time, and I our free iPad app, both available at www.EM-News.com. could not determine the exact spe- Comments? Write to us at cifics. Importantly, if your dipsticks [email protected]. are scattered around the ED lab in an open container for more than two weeks, about three-quarters of them will give a false-positive res- Dr. Roberts is a pro- ult for nitrites. Perhaps the lab is with the ED reading for leukocyte each test alone is quite variable, fessor of emergency better at protecting dipsticks than ­esterase and the degree of from 60 to 88 percent, but a medicine and toxic- the ED, but I rarely see the top put ­hematuria. ­negative result is sufficiently ology at the Drexel back on the container in my ED’s The heterogeneity of dipstick ­predictive enough to exclude dis- University College stat lab. Everyone has difficulty accuracy for UTI is subject to on- ease. Dipstick results should be of Medicine in Phil- with quality control for dipstick going discussion. One exhaustive combined with clinical acumen, adelphia. Read the testing in the ED. We all now use meta-analysis concluded that the but send a urine culture when in Procedural Pause, a machines to read the dipstick urine dipstick test alone seems to doubt. blog by Dr. Roberts and his daugh- rather than relying on a nurse’s be useful in all populations to ex- Like most things in medicine, ter, Martha Roberts, ACNP, CEN, at eyeball, and a printout has re- clude infection if nitrites and leuk- the dipstick urinalysis is not as http://bit.ly/ProceduralPause, and placed the pen. Nonetheless, ocyte esterase are negative. (BMC straightforward as one would read his past columns at http://bit. our hospital lab often disagrees Urol 2004;4:4.) The sensitivity for like. It is clearly not foolproof or ly/RobertsInFocus.

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