Causes of Sterile Pyuria
Sterile pyuria is defined as the presence of white blood cells in urine (≥5 WBCs/hpf) without bacterial growth on standard culture media. This finding requires thorough evaluation as it may indicate various underlying conditions that need specific management approaches.
Common Causes of Sterile Pyuria
Infectious Causes
- Partially treated urinary tract infections: Prior antibiotic use may suppress bacterial growth while WBCs persist 1
- Atypical organisms not detected on standard culture:
- Tuberculosis (renal TB)
- Chlamydia trachomatis
- Ureaplasma urealyticum
- Mycoplasma genitalium
- Viral infections
Inflammatory/Autoimmune Conditions
- Systemic lupus erythematosus (SLE): 23% of SLE patients experience isolated sterile pyuria, with 78% showing concurrent non-renal disease activity 2
- Kawasaki disease: Sterile pyuria occurs in 30-80% of patients, particularly common in children ≤1 year of age 3
- Interstitial nephritis: Often medication-induced
- Glomerulonephritis: Various forms can present with sterile pyuria
Immune Checkpoint Inhibitor-Related Causes
- Immune checkpoint inhibitor (ICPi) nephritis: Presents as probable ICPi-related nephritis when there is:
- Sustained increase in serum creatinine ≥50% on consecutive values
- Absence of alternative etiology
- Sterile pyuria (≥5 WBCs/hpf) 4
Structural and Urological Causes
- Urinary tract stones
- Urinary tract malignancy
- Foreign bodies (including catheters)
- Genitourinary tuberculosis
- Polycystic kidney disease
Chronic Kidney Disease-Related
- Advanced CKD: Prevalence of asymptomatic pyuria increases with CKD stage (24.1% in non-dialysis CKD and 51.4% in hemodialysis patients) 5
- Over 70% of pyuria cases in CKD patients are sterile, likely due to chronic renal parenchymal inflammation 5
Medication-Induced Causes
- Analgesics (NSAIDs)
- Antibiotics
- Proton pump inhibitors
- Chemotherapeutic agents
- Diuretics
Other Causes
- Adjacent inflammation (appendicitis, diverticulitis)
- Radiation cystitis
- Vigorous exercise
- Contamination from genital tract secretions
Diagnostic Approach to Sterile Pyuria
Initial Assessment
Confirm sterile pyuria:
- Verify presence of ≥5 WBCs/hpf in urine
- Negative standard urine culture
- Rule out contamination from genital tract
Detailed history:
- Recent antibiotic use
- Medication history (focus on nephrotoxic drugs)
- Systemic symptoms (fever, weight loss, joint pain)
- Urinary symptoms (dysuria, frequency, urgency)
Laboratory evaluation:
- Complete urinalysis with microscopy
- Urine culture on standard media
- Consider specialized cultures for TB, fungi if indicated
- Assess renal function (creatinine, eGFR)
Advanced Testing Based on Clinical Suspicion
- For suspected TB: Acid-fast bacilli staining, TB-specific cultures, PCR
- For suspected chlamydia/mycoplasma: Specific PCR testing
- For suspected autoimmune disease: ANA, complement levels, anti-dsDNA
- For suspected structural abnormalities: Imaging studies (ultrasound, CT urography)
Management Considerations
Management should be directed at the underlying cause:
- Infectious causes: Appropriate antimicrobial therapy
- Autoimmune conditions: Disease-specific immunosuppressive therapy
- Medication-induced: Discontinuation of offending agent
- ICPi-related nephritis: Consider holding ICPi temporarily and consult nephrology 4
- Structural causes: Urological intervention as needed
Special Considerations
- In children with fever, sterile pyuria may indicate serious bacterial infection and requires thorough evaluation 4
- In patients with immune checkpoint inhibitor therapy, sterile pyuria may be an early sign of immune-related adverse events affecting the kidneys 4
- Persistent unexplained sterile pyuria warrants nephrology and/or urology consultation
Understanding the diverse etiologies of sterile pyuria is crucial for appropriate management and preventing long-term complications from underlying conditions.