What are leukocytes and nitrites, and how do they factor in a UTI diagnosis?

Urinary tract infection test strips are a quick, easy, and cost effective way to test for a UTI at home. The test works by testing for nitrites and leukocytes in the urine. When both nitrites and leukocytes come up as positive, it is very likely a UTI is present.

However, for many of us, we’ve had the experience of being uncertain about our test strip findings — do I really have a UTI? Here, we explore what exactly are leukocytes and nitrites, and how they are used to diagnose a possible UTI.

Leukocytes are also known as white blood cells, which are an important part of your immune system. Types of leukocytes include: granulocytes (which are made up of neutrophils, eosinophils, and basophils), monocytes, and lymphocytes (T cells and B cells). Together, all of these white blood cells help the body fight infection, inflammation, and other illnesses or diseases.  

When your body is fighting off an infection, your immune system will send white blood cells to combat any foreign invaders (think: bad bacteria). This is where checking the number of leukocytes (and their components) is a useful tool to help identify the presence of various conditions including infection or inflammation.

If your body’s white blood cells are increased, and are out of a ‘normal’ reference range* then, you guessed it, your body is likely fighting off some type of illness.

A leukocyte esterase (LE) test is just one such test, and is a compound that can be easily checked for on your urine dipsticks to screen for UTI, and can catch an asymptomatic (or early stage) infection. An LE test can also come back positive for infections such as Trichomonas and Chlamydia.

*Normal reference ranges can vary by lab. As always, consult with your doctor to see what reference ranges were used for your test and be sure to voice any concerns you may have.

So how does an LE test catch a UTI (or other infection) before you even notice it? This is because granulocytic cells all have esterases in them. Neutrophils (one of the types of granulocytes) are the first “cops on the scene” in an immune response, and their presence will be detected by an LE test even before you start to experience noticeable symptoms.

However, it’s important to note that white blood cells can be present in the bladder for other reasons (such as inflammatory disorders), and sometimes even after antibiotic therapy, so a positive LE test does not necessarily mean there are bacteria present (1).

On the other hand, when an individual has a suppressed or compromised immune system, leukocyte production is naturally low. This results in a low or negative LE test in patients despite presence of an infection. For these individuals, different testing methods may be warranted (such as a blood test) (2).

On occasion, a false-positive LE test result is possible. A false-positive result can be caused by various factors including:  

• oxidizing agents (such as bleach used in the manufacturing of dipsticks)
• when the urine is colored (which could be caused by drugs like Nitrofurantoin/Macrobid, supplements, and/or diet)
• bilirubin (liver disease)
• gross hematuria (or blood)
• AZO products (from my observations, AZO products color the supposing and can interfere with any test because of the color change)

A “dirty catch” urine sample may also contaminate a specimen with leukocytes from the vagina, which is why you may be asked to clean yourself and catch urine midstream; however, the current scientific evidence suggests that cleansing procedures may not be necessary as they have not been shown to decrease urine contamination significantly. (3, 4)  

Conversely, a false-negative result may also occur on occasion. A false-negative result could be influenced by (5):

• antibiotic use
• elevated sugar levels in the urine
• vitamin C (ascorbic acid) in large amounts
• menstrual blood
• concentrated urine
• strenuous exercise
• old infections (because the type of leukocyte that appears later in the infection is lymphocytes, which do not contain LE)

First, it’s important to know that nitrates are compounds normally found in urine, and may have a higher presence in some individuals depending on dietary patterns (some vegetables, like spinach, are naturally rich in nitrates). And if you’re still wondering what nitrate is - try to think back to that science class where you learned about the Nitrogen Cycle. The Nitrogen Cycle is important for all living organisms, and is something humans contribute to by eating foods rich in nitrate (a compound of 1 nitrogen and 3 oxygen molecules). That’s the really simplistic version, but hopefully helps to set the stage for the rest of this section.

When specific bacteria enter the urinary tract (such as E. coli, a common bacteria found in your gut), those dietary nitrates will be converted into nitrite (a compound of 1 nitrogen and 2 oxygen molecules). Because these specific bacteria can reduce nitrate to nitrite, infections with these organisms may show a positive nitrite result on the dipstick.

The usefulness of the nitrite test is limited, however, as nitrite production is not associated with other urinary tract pathogens such as Pseudomonas or even enterococci. (6)

A test for nitrites can also come back negative if the urine is excreted before the reduction of nitrate to nitrite can take place. Some references estimate this reaction can take up to 4 or 6 hours! (7,8) As we all know, it’s very difficult to hold urine when we have a UTI.

Just like with the LE test, false-negative nitrite results can occur and can be influenced by the following:

• when there is a low amount of nitrate in the urine due to low dietary nitrate intake
• high concentrations of vitamin C
• if the conversion of nitrite to nitrogen has occurred (for example, in specimens that have not been tested for several hours)
• urine having an acidic pH (<6.0)

False positives can occur when:

• dipsticks have been stored improperly or exposed to air
• conversion of nitrate to nitrite due to bacterial contamination in an improperly collected or stored urine specimen
• AZO use (your urine should be tested before any AZO use)
• gross blood (from my observation, because of the color, it can give a false positive on any test)

Bottom line is a negative nitrite value does not necessarily mean there is no infection present. It may only indicate the type of bacteria that are, or are not, present, assuming proper storage and handling conditions were met. So, as with everything, check with your doctor about what standard reference ranges are being used to determine any abnormal presence.

Sometimes results can show a negative LE and a positive nitrite. As already discussed, this could be caused by improper storage of the dipsticks or urine or could happen if the patient is immunocompromised. One thing that can be done to show a more precise dipstick result is to make sure the dipsticks are stored properly, and ensure the doctor knows if you have been diagnosed with an immune-compromising disorder and/or an illness requiring immune-suppressing therapies (such as lupus).

Again, if you have any questions regarding your test results, please talk with your doctor ASAP, especially if your symptoms are unresolved or worsening. It’s okay to ask to have a sample of clean-catch urine to undergo microscopic evaluation of urine sediment or ask if other tests should be performed. From there, your doctor can decide whether a culture and/or antibiotic sensitivity test are needed based on the specimen results and symptoms.

And one more note: I work in a rural hospital/clinic, so we lab techs talk with the provider about what we see in the microscope. Sometimes we will advise them if a specimen is properly sampled and tested to perform a culture. Communication is most important!

1. Martina Franz, Walter H. Hörl, Common errors in diagnosis and management of urinary tract infection. I: Pathophysiology and diagnostic techniques, Nephrology Dialysis Transplantation, Volume 14, Issue 11, November 1999, Pages 2746–2753, https://doi.org/10.1093/ndt/14.11.2746

2. Ramakrishnan K & Scheid DC. Diagnosis and management of acute pyelonephritis in adults. Am Fam Physician. 2005 Mar 1;71(5):933-942.

3. Simerville JA, Maxted WC, Pahira JJ. Urinalysis: a comprehensive review. Am Fam Physician. 2005 Mar 15;71(6):1153-1162.

4. Michael L. Wilson, Loretta Gaido, Laboratory Diagnosis of Urinary Tract Infections in Adult Patients, Clinical Infectious Diseases, Volume 38, Issue 8, 15 April 2004, Pages 1150–1158, https://doi.org/10.1086/383029

6. Wilson ML & Gaido L. Laboratory diagnosis of urinary tract infections in adult patients. Clin Infect Dis. 2004;38(8):1150-1158. https://doi.org/10.1086/383029

7. Tiso M, Schechter AN. Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions [published correction appears in PLoS One. 2015;10(5):e0127490]. PLoS One. 2015;10(3):e0119712. Published 2015 Mar 24. doi:10.1371/journal.pone.0119712

8. Wilson ML & Gaido L. Laboratory diagnosis of urinary tract infections in adult patients. Clin Infect Dis. 2004;38(8):1150-1158. https://doi.org/10.1086/383029

9. Urinalysis and Body Fluids: A Colortext and Atlas, Karen Munson Ringsrud and Jean Jorgenson Linne, Copyright 1995.

10. Emergency Medical News, Urine Dipstick Testing has Limitations, but is Still Useful in the ED, James R. Roberts, MD, 11/17/2020.