Evaluation of the Sysmex UF-5000 automated urine flow cytometer for detection of urethral inflammation and clinical urethritis in men

Objective evidence of urethral inflammation is required to diagnose urethritis in men. Clinically, this is established by confirming urethral discharge on examination in symptomatic patients. Alternatively, laboratory approaches rely on identifying polymorphonuclear neutrophils (PMNs) from a urethral swab specimen or leukocyte esterase (LE) activity in urine. However, physical examination-based diagnosis may be subjective, collection of a urethral swab is invasive, and often painful, and LE has poor sensitivity. To address these limitations, we evaluated the white blood cell (WBC) parameter of the Sysmex UF-5000 automated urinary flow cytometer for the detection of urethral inflammation and clinician-diagnosed urethritis. Using 1,000 remnant male urine specimens from a sexual health clinic, we measured urinary WBC counts (WBC/μL) using the UF-5000, LE by urinalysis, and abstracted corresponding clinical data and urethral Gram stain results from the electronic medical record. Urinary WBC counts measured by the UF-5000 were significantly higher in men with urethral symptoms, LE ≥1+ status, a clinical diagnosis of urethritis, and strongly correlated with elevated and increasing urethral Gram stain PMN density. The UF-5000 demonstrated excellent diagnostic discrimination, yielding areas under the receiver operating characteristic curve (AUC) of 0.86 for Gram stain-defined urethral inflammation, and 0.90 for clinician-defined urethritis. Optimized thresholds provided >95% sensitivity for ruling out infection and >95% specificity for ruling it in, outperforming standard LE testing. In conclusion, the UF-5000 automated urine flow cytometer offers a robust, non-invasive alternative for male urethritis diagnosis. This approach could expand diagnostic reach-particularly for men who decline urethral swab collection-and warrants prospective clinical validation. IMPORTANCE: Male urethritis diagnostics are limited by the poor sensitivity of leukocyte esterase (LE) testing or the invasive nature of urethral swab collection for Gram stain microscopy. These limitations may create barriers to patient care and delay urethritis diagnosis. Automated urinary flow cytometry may overcome these limitations, but few studies exist. We analyzed 1,000 remnant male urine specimens to evaluate the Sysmex UF-5000 white blood cell (WBC) parameter for detecting urethral inflammation. Elevated urinary WBC counts strongly correlated with elevated WBCs on urethral Gram stain smear microscopy and positive LE. The UF-5000 outperformed LE for ruling in and ruling out urethral inflammation and clinical urethritis. Automated urinary flow cytometry is a powerful, non-invasive diagnostic approach that warrants prospective evaluation in point-of-care clinical studies.