What are the causes of sterile pyuria in a male patient?

Causes of Sterile Pyuria in Males

Sterile pyuria in males most commonly results from sexually transmitted infections (particularly Chlamydia trachomatis), partially treated urinary tract infections, immune checkpoint inhibitor-induced nephritis, urolithiasis, and urological malignancies.

Infectious Causes

Sexually Transmitted Infections

• Chlamydia trachomatis is the most important infectious cause in sexually active males, detected in 10% of sterile pyuria cases by PCR testing 1
• Mycoplasma genitalium, though less common (1% of cases), occurs exclusively in males with sterile pyuria 1
• Ureaplasma urealyticum accounts for 5% of sterile pyuria cases, with significantly higher rates in males compared to females 1
• These organisms are not detected by routine urine culture, requiring specific PCR testing for diagnosis 2, 1

Partially Treated Bacterial Infections

• Antibiotics started before urine culture collection can sterilize the culture while pyuria persists 3
• Acute pyelonephritis with insufficient bacterial counts to be detected on standard culture media can present as sterile pyuria 3

Drug-Induced Causes

Immune Checkpoint Inhibitor Nephritis

• Immune checkpoint inhibitor therapy causes nephritis presenting with increased serum creatinine and sterile pyuria (≥5 WBCs/hpf), requiring prompt recognition and management 3
• This represents an increasingly common cause given the widespread use of these cancer therapies 3

Structural and Inflammatory Causes

Urological Conditions

• Urolithiasis causes inflammation without infection, leading to sterile pyuria in males 3
• Benign prostatic hyperplasia is a male-specific cause of sterile pyuria through inflammatory mechanisms 3
• Urological malignancies (bladder, renal, ureteral) can cause inflammation and pyuria without infection 3

Glomerulonephritis and Interstitial Nephritis

• Glomerulonephritis presents with sterile pyuria as part of active renal disease 3
• Interstitial cystitis, though more common in women, can occur in males with chronic pelvic pain 3

Diagnostic Algorithm

Initial Laboratory Assessment

• Confirm pyuria with microscopic urinalysis showing >5-10 WBCs per high-power field 3
• Obtain urine culture on standard media to document absence of bacterial growth 3
• Check serum creatinine to assess for concurrent renal dysfunction 3

Targeted Testing Based on Clinical Context

• In sexually active males <35 years: Order PCR testing for Chlamydia trachomatis, Mycoplasma genitalium, and Ureaplasma urealyticum 2, 1
• In patients on immune checkpoint inhibitors: Evaluate for immune-related nephritis with serum creatinine and consider renal biopsy 3
• In patients with recent antibiotic use: Consider partially treated UTI and repeat culture after antibiotic completion 3
• In patients with flank pain or hematuria: Obtain imaging (ultrasound or CT urography) to evaluate for urolithiasis or structural abnormalities 3

Imaging Considerations

• CT urography or renal ultrasound should be performed when structural abnormalities, malignancy, or urolithiasis are suspected 3
• Imaging is particularly important in males >35 years with risk factors for urological malignancy (smoking, occupational exposures, gross hematuria) 4

Critical Clinical Pitfalls

Common Diagnostic Errors

• Failing to test for sexually transmitted infections in young males is the most common missed diagnosis, as these organisms require PCR rather than routine culture 2, 1
• Attributing sterile pyuria to "contamination" without proper investigation delays diagnosis of significant pathology 5
• Not recognizing immune checkpoint inhibitor nephritis in cancer patients can lead to irreversible renal damage 3

Management Considerations

• Empiric antibiotics should not be given for sterile pyuria without identifying the underlying cause, as this obscures diagnosis 3
• In males with sterile pyuria and urethral symptoms, treat for Chlamydia even before PCR results return, given the consequences of untreated infection (epididymitis, prostatitis, partner transmission) 2
• Inadequate treatment of the index case leads to ongoing transmission and complications 2