What is leukocyte (white blood cell) esterase and its significance in a patient, particularly in those with a history of urinary tract infections (UTIs), diabetes, or impaired renal function?

What is Leukocyte Esterase?

Leukocyte esterase is an enzyme released by white blood cells (leukocytes) that is detected in urine through a dipstick test, serving as a marker for pyuria (white blood cells in urine) and helping to screen for urinary tract infections, though it cannot diagnose UTI on its own. 1, 2

Biochemical Basis

• Leukocyte esterase is an enzyme specifically released from white blood cells when they are present in urine 2
• The dipstick test uses a chemical reaction that produces a color change when leukocyte esterase is present, with results typically reported as negative, trace, 1+, 2+, or 3+ based on the intensity of the color reaction 2
• The test detects pyuria (≥10 WBCs per high-power field on microscopic examination) as a surrogate marker 1, 2

Diagnostic Performance

• Leukocyte esterase has moderate sensitivity of 83% (range 67-94%) but limited specificity of 78% (range 64-92%) for detecting UTIs when used alone 1, 2
• When combined with nitrite testing, sensitivity increases to 93% with specificity of 96%, making this combination one of the most reliable dipstick tests for UTI 2, 3
• The most important clinical utility is its excellent negative predictive value (approaching 100%): the absence of both leukocyte esterase and nitrite effectively rules out UTI in most patient populations 4, 2

Clinical Significance in Your Patient Populations

Patients with History of UTIs

• A positive leukocyte esterase indicates pyuria but requires clinical correlation with symptoms (dysuria, frequency, urgency, fever, gross hematuria) and urine culture for definitive UTI diagnosis 1, 2
• The presence of leukocyte esterase helps distinguish true UTI from asymptomatic bacteriuria, as it is typically absent in asymptomatic colonization 2
• Never treat based on positive leukocyte esterase alone without accompanying urinary symptoms, as this leads to unnecessary antibiotic exposure and resistance 2, 3

Diabetic Patients

• Diabetic patients require careful evaluation because they may lack typical signs and symptoms of infection 5
• False-negative results can occur with high urinary glucose or high specific gravity, which are common in poorly controlled diabetes 2
• In diabetic patients with suspected UTI, obtain urine culture before initiating antibiotics even with positive leukocyte esterase, as these patients have significant sequelae from untreated infections 5

Patients with Impaired Renal Function

• The test remains useful in patients with renal impairment, though interpretation requires clinical context 2
• In patients with neutropenia or, rarely, normal peripheral WBC count, significant bacteriuria may occur without pyuria, making leukocyte esterase falsely negative 4
• Ensure proper specimen collection (midstream clean-catch or catheterization) to avoid contamination, which causes false-positive results 2

Critical Interpretation Pitfalls

• Asymptomatic bacteriuria with pyuria is extremely common (15-50% prevalence in long-term care residents) and should NOT be treated 4, 2
• False-positive results occur with contaminated specimens, certain oxidizing agents, and some medications 2
• False-negative results may occur with high urinary glucose, high specific gravity, certain antibiotics, or in patients who void frequently (short bladder dwell time) 2
• The presence of pyuria has relatively low positive predictive value for actual UTI because many noninfectious causes of genitourinary inflammation produce pyuria 4, 2

Practical Clinical Algorithm

When leukocyte esterase is positive:

• First, assess for specific urinary symptoms (dysuria, frequency, urgency, fever >38.3°C, gross hematuria, new/worsening incontinence) 1, 2
• If symptomatic: obtain properly collected urine culture before starting antibiotics, then initiate empiric treatment 1, 3
• If asymptomatic: do NOT pursue further testing or treatment, as this represents asymptomatic bacteriuria 2, 3

When leukocyte esterase is negative:

• Combined with negative nitrite, this effectively rules out UTI in most populations (negative predictive value 82-91%) 2
• If strong clinical suspicion persists (fever, systemic signs), consider non-urinary sources or obtain properly collected specimen to rule out contamination 2
• In suspected pyelonephritis or urosepsis with systemic signs, proceed with culture despite negative leukocyte esterase 2