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Comprehensive Urine Analysis Interpretation for Medical Professionals

Labs and Diagnostics

The Urine analysis is frequently used in all types of medical settings: hospitals (ER, ICU, Inpatient floors), urgent care, and outpatient offices. In many cases, correct evaluation of the urine is quintessential in making the appropriate diagnosis. To provide additional data, many hospitals run the urine through a microscope, giving you exact details on the contents within the urine, and quantifying the results. With this article, you will be able to educate yourself on how to interpret and evaluate the standard UA with Microscopy.

INITIAL  ASSESSMENT

Before you even dip the urine or send it to the lab, the urine can tell quite a bit about the patient just by using your God-given senses.

Color

The color of the urine analysis is the easiest way to determine someone’s hydration status. Surprisingly, it can indicate other aspects of health as well.

Yellow-Amber: Normal urine varies from very clear yellow to a darker amber color. Generally speaking, the less hydrated you are – the more concentrated your urine is with nitrogenous waste and electrolytes – thus darker urine. The more hydrated you are, the more dilute it is, leading to clear yellow urine. The first void of the morning is typically darker and more concentrated – this is normal. However, darker urine throughout the day should prompt an increased need to drink water. 

Red: When we see red urine – we typically think of blood. And that may be the case in many different situations such as kidney stones (nephrolithiasis), UTIs, or glomerular damage. As little as 1mL of blood can cause a color-change, and the presence of red urine does not automatically mean large amounts of blood. Rhabdomyolysis can also cause myoglobin in the urine which has a red-brown appearance as well. However, there are various other factors which can cause red urine including certain foods such as Beets, Blackberries, and rhubarb; as well as different medications such as Propofol, Chlorpromazine, or Ex-Lax.

Orange-Red: You may see a neon orange-red from the antibiotic Rifampin used in the treatment of TB, or phenazopyridine (pyridium) used to treat bladder burning and discomfort during a UTI.

Other crazy colors: Other foods, drugs, and disease processes can turn urine every color of the rainbow. Certain UTIs can cause Green or purple urine, Fava beans can cause brown urine, amitriptyline or IV promethazine can cause blue urine. While these are very interesting, they are also super uncommon and you probably don’t need to commit them to memory.

Turbidity

Urine turbidity is how clear the urine is. Cloudy urine is very turbid, and clear urine is… well clear. When we see cloudy urine, we first think of infection which is very possible. Other causes of cloudy urine are casts, protein, and/or cellular debris from damaged kidneys.  

Smell

Yes, your nose can detect more about urine than just detecting if the patient recently ate asparagus.

Urine has somewhat of an aromatic smell, and stronger-smelling urine tends to indicate dehydration (concentrated urine). Infections tend to have a very distinct foul-smell of bacteria which is difficult to describe, but does smell like ammonia as the bacteria often split urea to form ammonia. Sweet-smelling urine may mean spilling of glucose into urine from hyperglycemia. Lastly, If the urine smells like feces, a fistula might have formed somewhere between the GI tract and the Urinary tract. 

Taste

Nah I’m just kidding – but did you know they used to taste urine to detect glucose in the urine?…. GROSS

 

URINARY DIPSTICK

Specific Gravity

The specific gravity is how dilute or concentrated the urine is. The normal range for this is 1.005 (being very dilute) to 1.030 (very concentrated). This can give the interpreter a pretty good idea of hydration status during the unine analysis process. 

Test Considerations:

  • Protein, ketones, and glucose, as well as recent high-density radioopaque IV dyes, can falsely elevate the specific gravity.

Clinical Significance:

  • Levels within the normal range indicate hydration status, 1.005 being very hydrated and 1.030 being very dehydrated.
  • Levels below the normal range may indicate diabetes insipidus, renal failure, pyelonephritis, glomerulonephritis, psychogenic polydipsia, or malignant hypertension
  • Levels above the normal range may indicate severe dehydration, hepatorenal syndrome, heart failure, renal artery stenosis, shock, or SIADH.

pH

pH is a chemistry acronym which stands for potential of hydrogen. The more hydrogen ions there are, the more acidic something is. The pH scale runs of 0-14, with lower numbers being more acidic, and higher numbers being more basic. Normal urinary pH tends to be about 6 but runs as low as 4.5 and as high as 8. Because the kidneys regulate your acid/base balance, any change within the body should show up in your urine. However, various different disease processes can interfere with your kidney’s ability to do this effectively.

Test Considerations:

  • Diet: Cranberries and high-protein diets can cause acidic urine, whereas citrus fruits and low-carb diets can cause alkaline urine
  • Medications: Sodium bicarbonate and thiazide diuretics can cause more basic urine

Clinical Significance:

  • Metabolic acidosis: Any excess hydrogen ions (acidity) should be secreted by the kidneys into the urine, causing a lower pH (<5.3). 
  • Kidney Stones:
    • Alkaline urine typically is typically associated with Calcium oxalate, Calcium phosphate, Magnesium-ammonium phosphate, and staghorn calculi.
    • Acidic urine typically is associated with uric acid and cystine calculi.
  • UTIs: Urea-splitting bacteria such as Proteus and Klebsiella cause a more alkaline urine (between 7.0-7.5).
  • Renal Tubular Acidosis: Differentiating renal tubular acidosis is beyond the scope of this post, but pH can be used to in the diagnosis and differentiating of RTA. 

Protein

The urine normally has <150mg/day of protein and is undetectable on a dipstick, but when this level exceeds 300mg/day, it will show up on a dipstick. The dipstick is specific for albumin (a type of protein). Any damage to the glomerular basement membrane will let albumin and other larger particles to pass through the membrane and into the urine. This is typically used to evaluate kidney damage in diabetics, people with Congestive Heart Failure (CHF), or other causes of kidney damage.

When protein is present in the urine analysis, it is transient (meaning its temporary), and are benign. Potential benign causes include dehydration, emotional stress, fever, heat injury, inflammation, intense activity, acute illness, or an orthostatic disorder. All other causes of proteinuria involve the kidney – specifically the glomerulus or the renal tubules. Damage can cause proteins (which are generally larger) to pass through where they normally wouldn’t.

Some common causes of glomerular proteinuria include Diabetic nephropathy, lupus nephritis, preeclampsia, various infections (HIV, hepatitis B, post-streptococcal glomerulonephritis), certain cancers, and certain drugs like Heroin, NSAIDs, and Lithium. Some causes of tubular proteinuria include interstitial cystitis, Sickle-cell, and nephrotoxicity from NSAIDs or antibiotics like aminoglycosides.

Test Considerations:

  • Urinary concentration will impact the results, so correlate with the Specific Gravity. Very dilute urine can lead to underestimation of protein, and very concentrated urine can lead to overestimation. 

Clinical Significance:

  • In general, the dipstick is a crude estimate and evaluation by 24-hr urine specimen is the standard of care for ongoing proteinuria. Once renal etiology is found, a Nephrology consult is warranted. 
  • In the acute setting, the dipstick for protein isn’t too informative as acute illness, inflammation, stress, and dehydration are common presentations and can cause a transient elevation in urinary protein. 

Heme

The test for heme is very sensitive and can detect down to 1-2 RBCs/HPF. Thus, a negative dipstick theoretically excludes hematuria (blood in the urine). There are many potential causes of hematuria including UTIs, STDs, trauma/irritation, glomerular damage, coagulopathies, kidney stones, and malignancy. 

Test Considerations:

  • Urinary ascorbic acid has been shown to cause false-negatives in some cases. Ascorbic acid is also known as Vitamin C – so intake of dietary vitamin C or supplements can potentially cause false-negatives to occur. Some dipsticks do add a chemical to neutralize this effect. Still, false-negatives are unlikely.
  • Potential False-Positives: Myoglobin (as during rhabdomyolysis), semen (recent ejaculation), alkaline urine >9.0, contamination from hemorrhoids, vaginal blood, or oxidizing compounds used to clean the perineum.
  • Requires urine microscopy for confirmation.

Clinical Significance:

  • If the patient is >50 years old and has persistent hematuria, they should be evaluated for malignancy.
  • If hematuria also presents with casts and proteinuria – glomerular damage is likely.
  • If hematuria presents with leukocyte esterase, WBCs, and possible nitrites – consider hemorrhagic cystitis

Leukocyte Esterase

Leukocyte esterase is a component of WBCs which is released when these cells are lysed. The presence of leukocyte esterase supports the diagnosis of a Urinary Tract Infection (UTI)

Test Considerations:

  • False-Negative: Proteinuria, glucosuria, excessively concentrated urine, or tetracycline.
  • False-Positive: Contamination with vaginal discharge, certain medications (ampicillin), salicylate toxicity, and strenuous exercise.

Clinical Significance:

  • Presence supports the diagnosis of UTI, whereas its absence means infection is unlikely.

Nitrites

Nitrates are present in the urine at baseline. Some species of bacteria, specifically of the enterobacteriaceae species (E. coli, Klebsiella, Proteus, Enterobacter, Citrobacter, and Pseudomonas), release an enzyme called nitrate reductase which converts urinary nitrate to nitrite.

Test Considerations:

  • Certain bacteria produce low levels of nitrate reductase such as enterococus, and many bacteria do not produce any.
  • This reaction requires dwelling time within the bladder to occur. Urinary frequency or the presence of a Foley catheter can make this impossible. It can take up to 4 hours of dwelling before nitrites are detected. 
  • A person might not intake a sufficient amount of nitrates in their diet.
  • False-Positive: Azo dye metabolites and bilirubin, as well as letting the urine sit for too long can produce false-positives. Higher specific gravity reduces the sensitivity.
  • False-Negative: Ascorbic acid can produce false-negative.

Clinical Significance:

  • If negative, it really doesn’t mean much. If positive, then it is highly likely an infection is present.

Glucose

When serum glucose spills into the urine – this is termed glucosuria. Typically, this does not occur until the kidney glucose threshold is reached – which is around 180mg/dL. As you can tell, this can be useful for evaluating hyperglycemia in the setting of diabetes. However, periods of stress or fever have been known to cause small amounts of glucose within the urine as well.

Test Considerations:

  • Ascorbic Acid (vitamin C) has been known to cause false-negatives.

Clinical Significance:

  • Glucosuria can indicate hyperglycemia in undiagnosed diabetics when blood-work is not obtained.

Ketones

Ketones are released from fat cells when fat metabolism is increased. Most notably this occurs with DKA on a massive scale. However, ketones may also be present in low-carb ketogenic diets when dietary carbohydrates are kept below 50 grams per day, as well as in the setting of starvation (such as during a acute illness).

Bilirubin

Urinary bilirubin may be present in low amounts, but increased levels are due to abnormalities of bilirubin metabolism or liver function. Other causes include hepatitis, hepatobiliary obstruction (gallstones), hemolysis, liver parenchymal disease, constipation, intestinal bacterial overgrowth. Must be tested immediately as bilirubin is unstable, especially when exposed to light. 

Clinical Significance:

  • The presence of bilirubin may indicate elevated LFTs, but overall does not seem to add significant information toward diagnosis

Urinary Microscopy | Woman looking at slide under microscopeURINARY MICROSCOPY

Crystals

Crystals, as the name implies, are crystallizations within the urine. These can be normal as long as they are composed of substances normally found within the urine.

Clinical Significance:

  • Ethylene glycol ingestion: Typically presents with calcium oxalate crystals (“envelope-shaped”) and acute kidney injury
  • Tumor Lysis Syndrome: Presents with large amounts of uric acid crystals (“diamond” or “barrel” shaped) and acute kidney injury
  • Gout: May see uric acid crystals
  • Cystinuria: Present with cystine crystals (“hexagonal”)
  • UTIs: Magnesium ammonium phosphate and triple phosphate crystals (struvite) are “coffin-lid” shaped and seen with UTIs caused by urea-splitting organisms such as Proteus and Klebsiella.

Microorganisms

Bacteria are NOT normally found in the urine as it should be a sterile environment. If found, it can indicate infection or contamination.

Test Considerations:

  • Bacteria multiply rapidly if the urine specimen is left standing for too long at room temperature.

Clinical Significance:

  • If there are leukocyte esterase and possible nitrites present with <15-20 epithelial cells/HPF, then infection is highly likely. Consider starting empiric antibiotics if symptomatic and obtain a culture and sensitivity for confirmation.

Cells

RBC: Normally there are less than 2 RBCs/hpf. Microscopic hematuria is defined as the presence of at least 3 RBCs/HPF. Microscopic hematuria confirms a heme+ dipstick.

WBC: 2-5 WBCs/HPF or less is normal within the urine. If higher, indicates possible infection, inflammation, or contamination. Most of the WBCs found in the case of infection are neutrophils.

Epithelial: Squamous epithelial cells are the skin cell of the external urethra. >15-20 cells/HPF indicate contamination.

Casts

Casts are tube-like protein structures made of of various cells. Low urine pH, low urine flow rate, and high urinary salt concentration promote cast formation by favoring protein denaturation and precipitation. The presence of casts, other than hyaline casts, represents pathology within the kidney itself.

Hyaline casts: These can be present in normal healthy adults and are nonspecific. They can be found after strenuous exercise or dehydration, as well as with diuretic use.

RBC casts: Likely indicate glomerulonephritis or vasculitis.

WBC casts: Uncommon, but when present is usually seen with tubulointerstitial nephritis and acute pyelonephritis, but also seen with renal tuberculosis and vaginal infections. 

“Muddy-brown” granular casts: are diagnostic of acute tubular necrosis, the leading cause of Acute Kidney Injury.

Waxy casts: Consistent with acute or chronic renal failure.

Broad casts: Consistent with advanced renal failure.

Fatty casts and lipiduria: Indicates Nephrotic syndrome

Renal tubular epithelial casts: seen in acute tubular necrosis, acute interstitial nephritis, and proliferative glomerulonephritis

Conclusion

Hopefully this gives you a pretty good idea of how to interpret the urine analysis. Whether you are a nurse, advanced practice provider, or physician, this skill is important to have and can aid in adequate patient care delivery. If there are any other diagnostic interpretations you would like to see, please leave a comment below!

References:
  1. Carroll, M. F., & Temte, J. L. (2000). Proteinuria in adults: A diagnostic approach. American Family Physician, 62(6), 1333-1340. Retrieved April 1, 2018, from https://www.aafp.org/afp/2000/0915/p1333.html.
  2. Fischbach, F. T., & Dunning, M. B., III. (2009). Manual of laboratory and diagnostic tests (8th ed.). Wolters Kluwer Health.
  3. Lerma, E. V. (2015). Urinalysis. Medscape. Retrieved April 1, 2018, from https://emedicine.medscape.com/article/2074001-overview
  4. Tintinalli, J. E., Stapczynski, J. S., Ma, O. J., Cline, D., Meckler, G. D., & Yealy, D. M. (2016). Tintinallis emergency medicine: A comprehensive study guide (8th ed.). New York: McGraw-Hill Education.
  5. Walk, R. W. (2018). Urinalysis in the diagnosis of kidney disease. In A. Q. Lam (Ed.), UpToDate. Retrieved April 1, 2018, from https://www.uptodate.com/contents/urinalysis-in-the-diagnosis-of-kidney-disease

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