Causes of Sterile Pyuria
Sterile pyuria is defined as the presence of white blood cells in the urine without bacterial growth on standard culture media. This condition requires thorough evaluation as it may indicate significant underlying pathology that needs specific management.
Common Causes of Sterile Pyuria
Immune-Related Causes
- Immune checkpoint inhibitor (ICI) therapy-related nephritis, which presents with increased serum creatinine and sterile pyuria (≥5 WBCs/hpf) 1
- Kawasaki disease, particularly common in children ≤1 year of age, with sterile pyuria occurring in 30-80% of patients 2
Infectious Causes
- Partially treated urinary tract infections where antibiotics have been started before urine culture 1
- Chlamydia trachomatis infection, especially in young, sexually active individuals 3
- Renal tuberculosis, presenting with fever, frequency, urgency, dysuria, and hematuria with sterile pyuria 4
- Viral infections affecting the urinary tract 5
Inflammatory Conditions
- Interstitial cystitis, particularly in women with chronic pelvic pain 1
- Glomerulonephritis and other renal parenchymal diseases 1
- Acute pyelonephritis with insufficient bacterial counts to be detected on standard culture 1
Structural and Urological Causes
- Urolithiasis (kidney stones) causing inflammation without infection 1
- Benign prostatic hyperplasia in men 1
- Urological malignancies that can cause inflammation 1
- Vesicoureteral reflux, particularly in children 2
Drug-Induced Causes
- Immune checkpoint inhibitors causing immune-related nephritis 1
- Analgesic nephropathy from chronic use of pain medications 1, 5
- Various medications that can cause chemical irritation of the urinary tract 5
Diagnostic Approach
Initial Evaluation
- Urinalysis with microscopic examination to confirm the presence of pyuria (>5-10 WBCs per high-power field) 1
- Urine culture using standard media to confirm sterility (absence of bacterial growth) 1
- Assessment for symptoms of UTI including dysuria, frequency, urgency, and flank pain 1
Further Investigations Based on Clinical Suspicion
- For suspected tuberculosis: Early morning urine samples for acid-fast bacilli and TB culture 4
- For suspected chlamydial infection: Specific testing for Chlamydia trachomatis 3
- For suspected immune-related adverse events: Evaluate recent medications, particularly immune checkpoint inhibitors 1
- For suspected structural abnormalities: Consider imaging studies such as ultrasound or CT urography 1
Clinical Pitfalls and Caveats
- Sterile pyuria in the setting of symptoms suggestive of UTI may represent infection with organisms that don't grow on standard culture media 5
- The presence of sterile pyuria in patients on immune checkpoint inhibitor therapy should raise suspicion for immune-related nephritis, which requires prompt management 1
- In children with sterile pyuria and fever, consider Kawasaki disease in the differential diagnosis, especially in those under 1 year of age 2
- In young, sexually active patients with sterile pyuria, always consider chlamydial infection, which requires specific testing 3
- Patients with renal tuberculosis typically present with hematuria and sterile pyuria, and this diagnosis should be considered in the differential diagnosis of unexplained hematuria 4
By systematically evaluating the potential causes of sterile pyuria based on patient demographics, clinical presentation, and risk factors, clinicians can identify the underlying etiology and implement appropriate management strategies.