Urinalysis and cancer

ALSO KNOWN AS: UA, routine urinalysis, complete urinalysis

DEFINITION: A routine complete urinalysis is the physical, chemical, and microscopic urine examination and a comprehensive overview of kidney function.

Cancers diagnosed: While urinalysis is the most cost-effective and least invasive evaluation of kidney and urinary tract function, it is not a screening method for the detection of cancer. Suspicious cells may, however, be seen upon microscopic review of the urine sediment, which is forwarded for cytological examination and further pathology review to rule out bladder or kidney cancer.

Why performed: Urinalysis is the most critical evaluation of kidney function. It may detect urinary tract infections and systemic diseases such as diabetes mellitus, glomerulonephritis, and malignancy.

Patient preparation: First morning voided urine of a minimum of 10 milliliters (ml) is the preferred specimen for a urinalysis. A random urine sample taken at any time during the day is acceptable. The patient collects the urine sample at midstream while urinating. The urine sample may also be obtained through bladder catheterization through the urethra or, rarely, through a suprapubic transabdominal needle aspirate of the bladder.

If the physician suspects a urinary tract infection, the urine must be a clean-catch sample in which contaminating bacteria are absent. For more detailed studies, a twenty-four-hour urine specimen may be required. A sample contaminated by vaginal discharge or hemorrhage will be rejected for analysis.

Steps of the procedure: After the patient voids the urine sample into a cup or other container, it is labeled and sent to the clinical laboratory. A sample might have to be collected again if the transport to the clinical laboratory has been delayed, the quantity needs to be increased, or there is bacterial overgrowth.

The clinical laboratory completes three evaluations of the urine. The physical characterization of the urine includes a description of the color (pale yellow, yellow, red-orange, or brown), appearance or transparency (clear to cloudy to opaque), odor if abnormal, and specific gravity. The chemical evaluation includes the pH, protein, glucose, occult blood, ketones, leukocyte esterase, nitrite, bilirubin, and urobilinogen. These chemistry detection systems are each impregnated on a series of reagent pads on a dipstick that are activated when dipped into the urine and can be read manually or with an instrument. The microscopic examination of the urine sediment looks for bacteria, cells, and other formed elements such as casts, squamous epithelial cells, and crystals.

After the procedure: The urine sample is analyzed as soon as possible after voiding, ideally in less than two hours after collection. The results are sent to the physician who ordered the test.

Risks: There are no risks to collecting a routine urine sample other than inconvenience.

Results: Fresh normal urine is sterile, pale to dark yellow or amber, clear, and faintly aromatic. Its specific gravity is between 1.003 and 1.035 grams per ml, and its pH is 4.5 to 8.0. The dipstick chemistries are negative, and cells or other elements are absent from the microscopic examination. The normal twenty-four-hour urine volume is 750 to 2,000 ml.

Urine from a healthy individual is yellow to amber in color. Pale urine may suggest diabetes insipidus. Milky urine may be caused by fat globules or white cells in a urinary tract infection. Red urine may result from red blood cells, medications, or certain foods. A greenish urine suggests the presence of bile associated with jaundice. A brown/black urine suggests hemorrhage or poisoning.

Normal urine is clear, through which newsprint can be read. Cloudy to turbid urine may result from the precipitation of mucin or calcium phosphates, neither of which merits pathological significance. Milky urine may suggest the pathological presence of fat globules. Turbid urine can point to a urinary tract infection.

Normally, urine presents a faintly acrid odor. Pleasantly sweet-smelling urine may suggest ketone production associated with diabetes mellitus. Strong acrid odors may result from medications or the ingestion of certain foods, like the acrid odor associated with asparagus.

The urinary specific gravity is a reliable indicator of a person’s hydration status. The body maintains a narrow acid-to-base ratio (pH) to sustain life. The kidney monitors metabolic activity, and excess acid or base ions are excreted in the urine to maintain that balance.

In healthy persons, protein is not present in urine in detectable amounts. Proteinuria is the excretion of more than 150 ml per day or 10 to 20 ml per deciliter of protein in the urine and is a classic symptom of renal disease. Proteinuria may be transient or persistent. If the proteinuria is persistent, then additional studies will determine if the cause is glomerular, tubular, or the result of overflow in which low-molecular-weight proteins overwhelm the ability of the system to reabsorb filtered proteins.

In healthy persons, glucose is filtered by the glomerulus and reabsorbed in the proximal tubule. Glucose appears in the urine when it overwhelms the tubule's ability to reabsorb it. Further evaluation determines the source of glycosuria—diabetes mellitus, Cushing's syndrome, liver and pancreatic diseases, or Fanconi syndrome.

A positive test for occult blood indicates the presence of hemoglobin or myoglobin. A finding of blood in the urine chemistry and the presence of red blood cells in the microscopic examination of urinary sediment (hematuria) requires the clinician to determine the source of the bleeding. Hematuria may be caused by an infection, glomerular, tubular, renovascular, or metabolic disorders, tumors, or calculi (stones). It may also be induced by exercise, such as long-distance running.

Ketones are the end products of the body’s fat metabolism and are usually undetectable in the urine. The clinician determines the cause of the presence of ketones (ketonuria)—carbohydrate-free dieting, uncontrolled diabetes, or starvation.

Freshly voided urine is usually sterile. However, in urinary tract infections and subsequent pyuria, the white blood cells produce leukocyte esterase, detected on the dipstick reagent strip. A healthy person does not have nitrites in the urine. In the case of a urinary tract infection, gram-negative and some gram-positive microorganisms reduce the nitrates in the urine to nitrites, which can be detected.

Normally, unconjugated bilirubin is water-insoluble and cannot pass through the glomerulus. Conjugated bilirubin is water soluble and appears in the urine, suggesting liver disease or biliary obstruction. The urine is also tested for urobilinogen, a colorless derivative of bilirubin formed by the action of intestinal bacteria.

Urinalysis also checks for microscopic formed elements. Except for an occasional epithelial, white, or red cell, the microscopic examination of normal healthy urine sediment is without comment. The following may suggest pathology and require clinical interpretation in the context of patient history—white blood cells (leukocytes), red blood cells (erythrocytes), casts, crystals, and bacteria.

Casts are cylindrical bodies with a protein matrix formed in the lumen of the renal tubules. They may demonstrate a homogenous or cellular matrix and include hyaline, waxy, erythrocyte, leukocyte, epithelia, bacteria, granular, fatty, or broad. Crystals result from the precipitation of urinary solute out of the urine. They are generally not present in freshly voided urine, and many are not clinically significant. Examples include calcium oxalate, uric acid, triple phosphate (struvite), and cysteine.

Five bacterial organisms per high-power field from a clean-catch urine sample is the classic diagnostic criteria for bacteriuria and a diagnosis of a urinary tract infection. Typically, five organisms per high-power field represent 100,000 colony-forming units when the urine is cultured.

Some tests, like the multiplex Oncuria test, use urinalysis to examine levels of a biomarker panel consistent with bladder cancer diagnoses, allowing a noninvasive and speedy detection method.

Bibliography

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"Can Bladder Cancer Be Found Early?" American Cancer Society, 12 Mar. 2024, www.cancer.org/cancer/types/bladder-cancer/detection-diagnosis-staging/detection.html. Accessed 20 July 2024.

Casler, Kelly Small, and Kate Gawlik. Laboratory Screening and Diagnostic Evaluation: An Evidence-Based Approach. Springer Publishing Company, LLC., 2023.

Hirasawa, Yosuke, et al. "Diagnostic Performance of Oncuria™, a Urinalysis Test for Bladder Cancer." Journal of Translational Medicine, vol. 19, 2021, pp. 1-10. doi.org/10.1186/s12967-021-02796-4.

Hoeh, Michael P., and Kalyan C. Latchamsetty. "Hematuria." Common Surgical Diseases. Springer, 2015, pp. 305–07.

Mundt, Lillian A., and Kristy Shanahan. Graff’s Textbook of Urinalysis and Body Fluids. 3rd ed., Jones & Bartlett Learning, 2020. 

Ridley, John W. Fundamentals of the Study of Urine and Body Fluids. Springer, 2018. 

Strasinger, Susan King, and Marjorie Schaub Di Lorenzo. Urinalysis and Body Fluids. 5th ed., F. A. Davis, 2008.