Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Urine Biomarkers Individually and as a Consensus Model Show High Sensitivity and Specificity for Detecting UTIs

Version 1 : Received: 29 June 2023 / Approved: 30 June 2023 / Online: 3 July 2023 (14:35:23 CEST)

A peer-reviewed article of this Preprint also exists.

Akhlaghpour, M.; Haley, E.; Parnell, L.; Luke, N.; Mathur, M.; Festa, R.A.; Percaccio, M.; Magallon, J.; Remedios-Chan, M.; Rosas, A.; et al. Urine Biomarkers Individually and as a Consensus Model Show High Sensitivity and Specificity for Detecting UTIs. BMC Infectious Diseases 2024, 24, doi:10.1186/s12879-024-09044-2. Akhlaghpour, M.; Haley, E.; Parnell, L.; Luke, N.; Mathur, M.; Festa, R.A.; Percaccio, M.; Magallon, J.; Remedios-Chan, M.; Rosas, A.; et al. Urine Biomarkers Individually and as a Consensus Model Show High Sensitivity and Specificity for Detecting UTIs. BMC Infectious Diseases 2024, 24, doi:10.1186/s12879-024-09044-2.

Abstract

We aimed to determine if infection-associated urine biomarkers can differentiate true urinary tract infection (UTI) from non-UTI controls. Midstream clean-catch urine samples were collected from asymptomatic volunteers and symptomatic subjects > 60 years old diagnosed with presumptive UTI in a specialty setting. Microbial identification and density were assessed using multiplex PCR/pooled antibiotic susceptibility test (M-PCR/P-AST) and standard urine culture (SUC). Three biomarkers (NGAL, IL-8, and IL-1β) were measured in the same urine specimens. Definitive UTI cases were symptomatic and had positive microorganism detection by SUC and M-PCR, while definitive non-UTI cases were asymptomatic volunteers regardless of microbial detection. We observed a strong positive correlation (R2 ≈ 1) between microbial density and the biomarkers NGAL, IL-8, and IL-1β. Biomarker consensus criteria of two or more positive biomarkers had sensitivity 90.2%, specificity 91.2%, positive predictive value (PPV) 91.7%, negative predictive value (NPV) 89.7%, accuracy 90.7%, positive likelihood ratio of 10.28, and negative likelihood ratio of 0.11 in differentiating definitive UTI from non-UTI cases, regardless of microbial density. NGAL, IL-8, and IL-1β showed a significant elevation in symptomatic cases with positive microbe identification compared to asymptomatic cases with or without microbe identification. Biomarker consensus exhibited high accuracy in distinguishing UTI from non-UTI cases.

Keywords

Keywords: urinary tract infection (UTI); diagnostic testing; urine biomarkers; neutrophil gelatinase-associated lipocalin (NGAL); interleukin (IL)-8, IL-1β

Subject

Medicine and Pharmacology, Urology and Nephrology

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