Urinalysis is a simple, inexpensive means of detecting urologic and systemic conditions such as infection, urolithiasis, malignancy, and metabolic diseases. Urinalysis can be outsourced or performed in the office by clinical staff. Familiarity with a visual inspection of the urine, dipstick testing, and point-of-care microscopy is an important diagnostic skill for family physicians. This article reviews and updates the practical use of office-based urinalysis and the differential diagnosis for abnormal results.

Setting Up In-Office Urinalysis

Urine dipstick test kits are widely available and easy to use. Results may be interpreted visually off the dipstick or by an automated machine.¹ Microscopic analysis requires a centrifuge and microscope, with commonly used 10×, 40×, and 100× (oil immersion) objectives. Phase-contrast and polarized microscopes help identify casts and crystals, respectively, but are not commonly used in office settings.²

The Clinical Laboratory Improvement Amendments (CLIA) regulate medical testing, and dipstick urinalysis can be performed in a physician’s office by obtaining a CLIA certificate of waiver. Clinician-performed microscopy is considered moderate complexity testing and requires a demonstration of quality assurance by proficiency testing or split sampling.² The American Academy of Family Physicians has published detailed guidance for navigating this process.³

Specimen Collection

The American Society for Microbiology recommends midstream urine collection with genital cleansing when possible, regardless of age and sex, despite a lack of evidence that this strategy decreases contamination.⁴ The American Urological Association also recommends midstream collection for evaluation of microhematuria.⁵ Urine should be refrigerated or tested promptly after collection to avoid incorrect results.⁶

In clinically stable infants and children, the initial urinalysis can be performed using a convenient collection method, such as a urine collection bag specimen. Urine culture of a bag specimen is not recommended. Alternatively, successful midstream urine collection has been described using suprapubic and lumbosacral stimulation, such as the Quick-Wee approach.⁷ If urinalysis shows the presence of leukocyte esterase or nitrites, follow-up urinalysis using clean urine collection by urethral catheterization or suprapubic aspiration should be performed.⁸ An online risk calculator can help in the assessment of urinary tract infection (UTI) in infants (https://uticalc.pitt.edu).

Visual Appearance and Odor

The yellow color of urine is caused by urochrome generated from the breakdown of hemoglobin. Foods, drugs, metabolic products, and infections can cause an abnormal urine appearance (Table 1).^6,9–11 Cloudy urine suggests an infection (positive likelihood ratio = 3) but can indicate alkaline urine with precipitated phosphate crystals.^6,12 Gross hematuria is concerning for malignancy. Visible feces in the urine can suggest an enterovesical fistula, whereas nonfeculent brown urine may indicate ingestion of fava beans. Fluorescence by Wood lamp can demonstrate porphyrins in heme biosynthesis disorders. Purple urine bag syndrome can occur in patients with long-term indwelling catheters because of metabolites from certain types of bacterial overgrowth (Figure 1).¹¹

Dehydration leads to concentrated, strong-smelling urine. A fruity or sweet odor can indicate diabetic ketoacidosis. Foul smells such as ammonia can indicate a UTI or an infected kidney stone. Although a feculent odor suggests a fistula, a sulfur-like odor can be attributed to ingestion of a sulfa medication or asparagus.⁶

Dipstick Urinalysis

Dipsticks visually display results after a sufficient time in contact with urine. The color change is compared with a reference standard to determine the concentration of the analyte being measured.¹ The dipstick result is usually read after 60 to 120 seconds. The leukocyte esterase dipstick test is the most sensitive to time. Substances and medical conditions can also affect dipstick results. Nitrite results can be inaccurate when the dipstick is left unpackaged in the open air (Figure 2).

Table 2 includes the diagnostic, false-positive, and false-negative results that may occur with dipstick urinalysis.^1,6,13,14 Table 3 includes the accuracy of urinalysis in diagnosing UTI.^12,15

URINE SPECIFIC GRAVITY

The urine specific gravity shows concentrations of dissolved substances in the urine (osmolality). Dipstick urine specific gravity indicates only current hydration status. A value near 1.010 suggests euvolemia. A value exceeding 1.020 may indicate dehydration, glucosuria, or syndrome of inappropriate antidiuretic hormone. A value less than 1.003 suggests significant urinary dilution from diabetes insipidus, water intoxication, impaired renal function, adrenal insufficiency, or aldosteronism.^6,13,16

URINARY PH

The urinary pH may vary from 4.5 to 8, but it is often between 5.5 and 6.5 because of excreted acids from renal metabolic activity. A high pH may be due to a high citrate diet, type 1 renal tubular acidosis, or infection with urease-positive bacteria such as Proteus. A low pH can occur with diets high in protein and acidic fruits.^6,13 In patients with urolithiasis, the urinary pH can indicate the type of stone.¹⁴ A low pH occurs with uric acid, cystine, and calcium oxalate stones, and a high pH occurs with calcium phosphate and infected struvite/staghorn stones.¹⁴

BILIRUBIN AND UROBILINOGEN

Although unconjugated bilirubin is insoluble in water, conjugated bilirubin is soluble and can be excreted in urine. The presence of conjugated bilirubin on dipstick testing should prompt investigation for hepatobiliary disease. Urobilinogen is produced by the breakdown of bilirubin in the intestines. A trace amount of urobilinogen is often excreted in the urine; however, elevated levels on dipstick testing may indicate hemolysis or hepatic disease.⁶

GLUCOSE

The sodium-glucose cotransporter-2 (SGLT-2) in the proximal renal tubule normally reabsorbs glucose that passes through the glomerulus. When plasma glucose concentrations exceed 180 to 200 mg per dL (9.99 to 11.10 mmol per L), the transporters are overwhelmed, resulting in glucosuria. SGLT-2 inhibitors used for the treatment of type 2 diabetes mellitus can also cause glucosuria.¹⁷ Glucosuria without serum glucose elevations or SGLT-2 inhibitor use can be due to Fanconi syndrome, which is a rare disorder of the proximal tubule that leads to multiple electrolyte abnormalities.¹³

KETONES

Ketones are not normally found in urine. The presence of ketones can be attributed to increased fatty acid catabolism from inadequate nutrition, diabetic ketoacidosis, a ketogenic diet, and sometimes pregnancy.⁶

PROTEIN

Dipstick tests detect many proteins but are most sensitive to albumin (Table 4).⁶ A protein finding of 1+ or greater suggests glomerular injury.⁶ Dipstick testing that shows proteinuria should be followed by a quantitative test such as a spot urine albumin/creatinine ratio.¹⁸ A 24-hour urine collection is more cumbersome and subject to collection errors.

The differential diagnosis for proteinuria is broad (Table 5).^6,10 Proteinuria may be transient or persistent, and the source can be glomerular, tubular, or overflow. Benign causes of transient proteinuria such as orthostasis or exercise are common in asymptomatic patients, and the proteinuria may be resolved on repeat testing in the morning. Urine dipstick testing may not detect low-molecular-weight proteins such as light chain fragments in multiple myeloma (i.e., Bence Jones proteins).

LEUKOCYTE ESTERASE AND NITRITES

Leukocyte esterase and nitrites found on dipstick testing suggest a UTI. Leukocyte esterase is produced by neutrophils and may be present with inflammatory processes and infections.^6,13 In one study of 705 children with culture-confirmed UTI, 71% of patients were positive for leukocyte esterase; however, this percentage decreased to 44% in patients with Enterococcus or Klebsiella infection.¹⁹

Nitrites are created by nitrate-reducing bacteria, and their presence has a higher specificity than leukocyte esterase for detecting a UTI.²⁰ A few bacteria such as Enterococcus do not produce nitrites, leading to false-negative results.²¹ Bacteria need four hours in the bladder to produce nitrites; therefore, false-negative results are common with frequent urination, including in infants.¹³

BLOOD

Dipstick testing for blood detects peroxidase activity of red blood cells (RBCs) in the urine. These tests have a greater than 90% sensitivity for hematuria, but free hemoglobin and myoglobin can lead to false-positive results.^6,22 Microscopic analysis is the best way to confirm dipstick testing positive for blood.⁵ Hematuria can be due to glomerular or nonglomerular causes^6,23,24 (Table 6²³).

Microscopic Urinalysis

Microscopic examination of the urine in the office setting can confirm the presence of RBCs, white blood cells (WBCs), epithelial cells, and bacteria. Preparation for microscopy generally involves centrifuging 10 mL of urine for five minutes at 1,500 rpm or greater. After the clinician gently pours out the supernatant, the pellet is resuspended using a small amount of the leftover supernatant. A drop is placed on a clean slide with a coverslip and observed under low- and then high-power magnification while ensuring the field of view is representative.^6,13,24,25

RED BLOOD CELLS

Normal-shaped RBCs are small, round, and colorless on microscopy and are referred to as ghost cells (Figure 3).² Dysmorphic RBCs may have blebs or protrusions, including the spiked cell membranes of acanthocytes and the fragments of schistocytes. Dysmorphic RBCs suggest glomerular disease.²⁵

Microhematuria in adults is defined as three or more RBCs per high-power field on spun urine. In children, microhematuria is diagnosed with more than five RBCs per high-power field.^5,24,26 The risk of genitourinary malignancy is 3% in patients with microhematuria; therefore, cystoscopy and imaging are recommended in intermediate- and high-risk adults in the absence of a clear nonmalignant cause. Cystoscopy should be considered for adults at low risk with continued microhematuria, especially if a benign cause such as exercise, menses, or UTI has resolved.⁵

WHITE BLOOD CELLS

Neutrophils are the most common WBCs found in urine. On microscopy, neutrophils are larger than RBCs and contain nuclei. Neutrophils can be found in infectious and inflammatory processes, including UTIs, sexually transmitted infections, and urolithiasis.⁶ More than five WBCs per high-power field is consistent with UTI for patients who are symptomatic (Figure 4). A portion of the urine sample may be tested for sexually transmitted infections via nucleic acid amplification, and a first morning void sample without cleansing detects sexually transmitted infections better than the midstream clean-catch samples recommended for diagnosing UTI.²⁷ Urolithiasis should be suspected in patients with urinary WBCs and severe pain, RBCs, and urine crystals.

EPITHELIAL CELLS

Squamous cells line the distal one-third of the urethra and the vulva. The presence of more than five large squamous cells per high-power field suggests contamination with distal or extra-urethral flora. Even with contamination, hematuria or pyuria suggests UTI²² (Figure 4).

BACTERIA

Bacteria are difficult to see on microscopy unless abundant. Bacteria may be present with infection and contamination. A urine culture is required to evaluate for a dominant bacterial species (Table 7).^20,28–30 The presence of five bacteria per high-power field suggests that colony counts of 100,000 per mL will be found on urine culture.³¹ Urine culture is recommended when UTI symptoms are present. Screening for asymptomatic bacteriuria is recommended only in pregnancy and before endoscopic urologic procedures.³² Asymptomatic bacteriuria is often unnecessarily treated in older patients.

CRYSTALS AND CASTS

Although most urinary crystals can be viewed with normal microscopy, some are better viewed with polarized microscopy (eFigure A). Crystals from monohydrated calcium oxalate, uric acid, and triple phosphate are birefringent under polarized microscopy. Urinary crystals can be useful in the diagnosis of urolithiasis. Crystal formation can occur in normal urine when cooled; therefore, only fresh urine samples should be analyzed for crystals.

The presence of casts in urine (eFigure B) suggests certain renal pathologies (Table 8⁶). Hyaline casts are made of protein and may be a normal finding or occur with renal disease. RBC and WBC casts confirm glomerular disease. Granular casts consist of protein or degraded cellular casts and may indicate tubular injury, such as acute tubular necrosis.^6,25

This article updates previous articles on this topic by Simerville, et al.,⁶ and Sharp, et al.²⁴

Data Sources: A PubMed search was completed in Clinical Queries using the key terms urinalysis, dipstick, and UTI. Also searched were Essential Evidence Plus, the Cochrane database, and reference lists in retrieved articles. Search dates: January 25, 2021, and January 25, 2022.

Figure 4, eFigure A, and eFigure B are courtesy of the National Institutes of Health Clinical Center Department of Laboratory Medicine, Bethesda, Md.