Sterile pyuria

What is sterile pyuria?

Sterile pyuria is the presence of elevated numbers of white blood cells (>10 white cells/mm³) in urine which appears sterile using standard culture techniques.¹

• Sterile pyuria is not an uncommon laboratory finding. In one population study, 13.9% of women and 2.6% of men were affected.²

• Sterile pyuria is often found in female patients with symptoms of urinary tract infection (UTI). However, these results may be misleading for various reasons:

  • Standard laboratory culture conditions may not be optimal for growth of atypical organisms.

  • Laboratory may not report significant growth either because it was not a single organism or a recognised urinary pathogen.

  • Fewer than 100,000 colony-forming units (cfu) per mL reported - for example, it may be that urine was diluted by high fluid intake or an organism may be slow-growing. Studies have shown that approximately half of women presenting with symptoms and counts of 100-10,000 cfu/mL have genuine bladder infections.

• The presence of pyuria increases the significance of a low bacterial count in the urine.

• Cell count per high power field is inaccurate and use of a counting chamber or similar gives more accurate results.

Causes of sterile pyuria (aetiology)

Sterile pyuria occurs when the immune system responds to an inflammatory stimulus in the urinary tract without the presence of bacterial infection. This response is often mediated by leukocytes (mainly neutrophils), which are typically involved in the defence against infections but can also be present in non-infectious inflammatory processes. Despite the absence of bacterial pathogens, sterile pyuria is indicative of an underlying pathological condition that could be infectious, non-infectious, or even functional in nature.

Infectious causes

• These include infections by pathogens that may not grow on standard urine culture, such as fungi like Candida species.³

• A recently (within preceding two weeks) treated urinary tract infection (UTI) or inadequately treated UTI.

• A sexually transmitted infection such as, Neisseria gonorrhoeae, chlamydia trachomatis or trichomonas vaginalis should be considered particularly in adolescents.⁴

• Renal tract tuberculosis.⁵

• Contamination of the sample with vaginal leukocytes.

Non-Infectious causes

These include a wide range of systemic and urological conditions such as:³

• Interstitial nephritis.

• Sarcoidosis.

• Renal papillary necrosis.

• Diabetes mellitus.

• Sickle cell disease.

• Analgesic nephropathy.

• Urinary tract neoplasm, including renal cancer and bladder cancer.

• Polycystic kidneys.

• Interstitial cystitis.

• Kawasaki disease.⁶

• Other reported associations include appendicitis and systemic lupus erythematosus.

Post-renal or functional causes

• Conditions like obstructive uropathy, which cause urinary stasis.

• False negative culture due to contamination with antiseptic.

• Urinary tract stones.

• Prostatitis.

Diagnosing sterile pyuria (investigations)

• Urinalysis: initial test to identify likely infection but a urine sample needs to be sent to the laboratory. See the separate Urine dipstick analysis article. Positive nitrite test +/- positive leukocyte esterase test. Haematuria and proteinuria occur in UTI but are also present in other conditions.

• Urine microscopy, culture and sensitivities; ask the laboratory to culture under conditions allowing identification of fastidious or slow-growing organisms.

• Consider the possibility of sexually transmitted infection; take a sexual history and consider sending swabs for chlamydia and N. gonorrhoeae.

• Polymerase chain reaction (PCR) testing of sterile pyuria has been recommended for the detection of Chlamydia trachomatis, mycoplasma and ureaplasma infections.⁷ However, in asymptomatic patients, the usefulness of mycoplasma and ureaplasma detection by this means has been questioned on the grounds that carriage of these bacteria is common, and the majority of individuals do not develop any disease.⁸

• Always consider tuberculosis; culture for AFBs (three early morning urine samples).

• With urine obtained direct from the bladder, any organism grown is significant and should be treated with a prolonged course of appropriate antibiotics.

• Ultrasound of kidneys, ureters and bladder should be considered for evaluation of febrile or otherwise symptomatic patients.⁹

• Cystoscopy may be required to exclude non-infective causes.

Management of sterile pyuria

Management of any identified underlying cause.