What can cause white blood cells (WBCs) in urinalysis without a urinary tract infection (UTI)?

White Blood Cells on Urinalysis Without Infection

Pyuria without bacteriuria represents a distinct clinical entity that is NOT a UTI and occurs in multiple non-infectious conditions including interstitial cystitis, chemical urethritis, nephrolithiasis, systemic inflammatory diseases, and kidney cyst infection in polycystic kidney disease. 1

Primary Non-Infectious Causes

Genitourinary Inflammatory Conditions

• Interstitial cystitis should be considered in women with chronic pelvic pain and pyuria, as this diagnosis is prevalent but often difficult to diagnose 1
• Chemical urethritis from irritants, soaps, or spermicides can cause sterile pyuria 1
• Nephrolithiasis causes pyuria in 14.2% of patients with renal colic, with 63.6% of these cases being sterile (culture-negative) 2
• Atrophic vaginitis in postmenopausal women may cause urinary symptoms and turbid urine, which may benefit from topical vaginal estrogen rather than antibiotics 1

Systemic and Infectious Causes

• Kawasaki disease and streptococcal infections can present with pyuria alone without bacteria 1
• Sexually transmitted infections (chlamydia, gonorrhea) causing urethritis present with sterile pyuria on standard urine culture 3
• Tuberculosis of the genitourinary tract causes persistent sterile pyuria 3
• Fungal infections may not grow on standard bacterial culture 3

Polycystic Kidney Disease-Specific

• Kidney cyst infection in ADPKD presents with fever, acute abdominal or flank pain, increased WBC count, and elevated C-reactive protein ≥50 mg/L 4
• Cyst hemorrhage must be differentiated from UTI, as both can cause pyuria and symptoms 4

Confirming True Absence of UTI

Diagnostic Criteria

• A true UTI cannot exist without BOTH bacteriuria AND pyuria—pyuria is the key distinguishing feature separating true UTI from asymptomatic bacteriuria 1
• Bacteriuria alone without pyuria indicates either external contamination, asymptomatic bacteriuria, or very rarely, extremely early infection before inflammation develops 1
• The absence of pyuria (negative leukocyte esterase combined with negative microscopy for WBCs) effectively excludes UTI with negative predictive value approaching 100% 1

Common Pitfall: Asymptomatic Bacteriuria

• Asymptomatic bacteriuria is frequently misdiagnosed as UTI, leading to unnecessary antibiotic treatment, and occurs in 10-50% of long-term care facility residents 1
• Asymptomatic bacteriuria does not require treatment in most populations and is distinguished from true UTI by the absence of symptoms despite both pyuria and bacteriuria being present 1
• Do not treat asymptomatic bacteriuria with antibiotics, even if pyuria is present, as this provides no clinical benefit and contributes to antibiotic resistance 3

Diagnostic Approach Algorithm

Step 1: Assess for UTI Symptoms

• If no specific urinary symptoms (dysuria, frequency, urgency, fever, gross hematuria) are present, do not pursue UTI testing or treatment 5
• Non-specific symptoms including confusion, incontinence, or functional decline in elderly patients are NOT reliable indicators of UTI 1

Step 2: Evaluate Specimen Quality

• High epithelial cell counts indicate contamination, which is a common cause of false-positive leukocyte esterase results 5
• If specimen quality is poor, obtain a properly collected specimen via midstream clean-catch or catheterization before making treatment decisions 5

Step 3: Interpret Urinalysis Results

• Pyuria with negative culture after 48 hours warrants evaluation for non-bacterial causes including STIs, tuberculosis, fungal infection, urolithiasis, or interstitial cystitis 3
• The presence of nitrite-negative results with negative culture practically excludes infection by gram-negative enterobacteria (E. coli, Proteus, Klebsiella) 5

Step 4: Consider Non-Infectious Workup

• Renal/bladder ultrasound is recommended to evaluate for stones or anatomic abnormalities in patients with recurrent sterile pyuria 5, 3
• In patients with suspected kidney cyst infection in ADPKD, obtain blood cultures and consider 18FDG PET-CT scan if confirmation is required 4
• Evaluate for sexually transmitted infections with appropriate testing (nucleic acid amplification tests for chlamydia/gonorrhea) in sexually active patients with sterile pyuria 3

Special Population Considerations

Elderly and Long-Term Care Residents

• Pyuria has low predictive value for UTI due to high prevalence of asymptomatic bacteriuria (10-50%) 1, 3
• Evaluate only with acute onset of specific UTI-associated symptoms, not with confusion or functional decline alone 5

Catheterized Patients

• Pyuria and bacteriuria are nearly universal in chronic catheterization and should not be treated unless systemic signs of infection develop 5
• Consider replacing the catheter before collecting specimens for more accurate assessment 3

Patients with Renal Colic

• The degree of pyuria correlates with risk of positive culture: 9.1% positive with 10-20 WBC/HPF versus 60.0% positive with >50 WBC/HPF 2
• Urine cultures are recommended for all patients with renal colic and pyuria to distinguish sterile inflammation from infection 2

What NOT to Do

• Do not interpret cloudy or smelly urine as infection in the absence of specific urinary symptoms 3
• Do not empirically treat with standard UTI antibiotics without identifying the causative organism when culture is negative, as this will not address non-bacterial causes 3
• Do not dismiss the diagnosis as "asymptomatic bacteriuria" when symptoms are present with pyuria—this indicates true inflammation requiring investigation 3
• Do not obtain urine culture in patients with turbid urine who lack dysuria, frequency, urgency, or systemic symptoms 1