Asymptomatic Bacteriuria or Urinary Tract Infection? New and Old Biomarkers

Martino, Francesca; Novara, Giacomo

doi:10.3390/ijtm2010006

Cited by 8 publications

(7 citation statements)

References 52 publications

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“…The biomarkers used in this study [neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-8), and interleukin-1-beta (IL-1β)] are essential components of the constitutive immune response in the urinary tract and have been studied in association with UTIs. Importantly, these three biomarkers have also demonstrated utility for the diagnosis of UTIs [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. One of our previous studies discovered that NGAL, IL-8, and IL-1β have sensitivities of 82.6%, 91.2%, and 69.8% with specificities of 90.8%, 76.8%, and 96.9%, respectively [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs

Parnell¹,

Luke²,

Mathur³

et al. 2023

Diagnostics

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The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic UTI patients aged ≥ 60 years and correlated them with detected levels of the immune response biomarkers neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-8), and interleukin-1-beta (IL-1β). The objective was to identify the microbial densities associated with significant elevation of these biomarkers in order to determine an optimal threshold for diagnosing symptomatic UTIs. Biobanked midstream voided urine samples were analyzed for microbial identification and quantification using standard urine culture (SUC) and multiplex-polymerase chain reaction (M-PCR) testing, while NGAL, IL-8, and IL-1β levels were measured via enzyme-linked immunosorbent assay (ELISA). NGAL, IL-8, and IL-1β levels were all significantly elevated at microbial densities ≥ 10,000 cells/mL when measured via M-PCR (p < 0.0069) or equivalent colony-forming units (CFUs)/mL via SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable than 100,000 CFU/mL for diagnosing UTIs.

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Section: Introductionmentioning

confidence: 99%

Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs

Parnell¹,

Luke²,

Mathur³

et al. 2023

Diagnostics

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“…Their study included a review of 4 previously published studies and suggested that uNGAL offered a promising and more sensitive alternative to the LE test for diagnosing UTI. Martino et al ( 12 ) conducted a systematic review of 4 published studies in an adult population and provided a summary of the results indicating encouraging performance of uNGAL. Horvath et al ( 10 ) summarized 16 studies on uNGAL for predicting UTI in both pediatric and adult population.…”

Section: Discussionmentioning

confidence: 99%

“…The most promising biomarkers identified were neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase 9 (MMP9), CXCL8 and interleukin-1β (IL-1β). While other targeted approaches over the years have additionally identified interleukin-8, tumor necrosis factor-α, and urine antimicrobial peptides ( 5 – 7 ) as putative predictors of UTI, the most promising and widely studied UTI biomarker is NGAL ( 8 – 12 ). Pre-clinical studies have established the biological, teleological, and functional roles of NGAL ( 13 – 18 ).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of diagnostic accuracy of urine neutrophil gelatinase-associated lipocalin in patients with symptoms of urinary tract infections: a meta-analysis

Zhang,

Chen,

Mitsnefes

et al. 2024

Front. Pediatr.

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IntroductionEarly and accurate diagnosis of urinary tract infection (UTI) can prevent serious sequelae including chronic kidney disease. Multiple individual studies have identified urine neutrophil gelatinase-associated lipocalin (uNGAL) as a promising biomarker for early diagnosis of UTI. We sought to understand the distribution and diagnostic accuracy of uNGAL values in patients presenting with UTI symptoms.MethodsOur systematic literature reviews in PubMed, Embase, and Cochrane Reviews up to March 2024, identified 25 studies reporting mean/median, standard deviation/quartiles, and detection limits of uNGAL in symptomatic patients with and without culture-confirmed UTI. Seventeen studies were in children. Meta-analyses were performed using the quantile estimation (QE) method estimating the distributions of uNGAL, which were then compared between the UTI and non-UTI groups for identifying the best cut-off points maximizing the Youden index. Sensitivity analyses were performed on all 25 studies including adult patients.ResultsWe found that uNGAL levels were significantly higher in samples with confirmed UTI compared to those without. In pediatric studies, median and 95% confidence interval (CI) of uNGAL values were 22.41 (95% CI of 9.94, 50.54) ng/mL in non-UTI group vs. 118.85 (95% CI of 43.07, 327.97) ng/mL in UTI group. We estimated the cut-off point of 48.43 ng/mL with highest sensitivity (96%) and specificity (97%) in children. Sensitivity analysis including both pediatric and adult studies yielded similar results.DiscussionThe level of uNGAL in symptomatic patients with confirmed UTI is much higher than that reported in patients without UTI. It may be used as a diagnostic tool to identify UTI early among symptomatic patients. The range of uNGAL concentrations and cut-off points reported in subjects with UTI is much lower than that reported in patients with acute intrinsic kidney injury.Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42023370451).

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“…The integration of these guidelines ensures a comprehensive and tailored approach to UTI management in kidney transplant recipients. Research into novel antimicrobial agents and immunomodulatory therapies, as well as the significance of innovative nonantibiotic-based approaches, may offer more targeted and effective options, mitigating the risk of infections while minimizing adverse effects [44][45][46][47][48].…”

Section: Management Of Urinary Tract Infections In Elderly Kidney Tra...mentioning

confidence: 99%

Effect of increasing age and ureteral stent implantation on urinary tract infections after kidney transplantation – update of recent literature

Omic,

Eder

2024

Current Opinion in Urology

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Purpose of review This review aims to present the recent literature regarding effects of aging and ureteral stent implantation (UrS) on the risk of urinary tract infections (UTIs) in kidney transplant (KTX) recipients. Recent findings UTIs in kidney transplant recipients remain a clinical challenge and represent a leading cause of morbidity, hospitalization rates, and mortality. Higher age was described as a significant risk factor for UTIs in several studies including a recent Brazilian analysis, indicating a 3.6%/years of age increase in UTI risk. Subsequently, a large meta-analysis, published in 2023, confirmed the correlation between older age and elevated UTI risk. The Swiss Transplant Cohort Study in 2022, largest of its kind, similarly confirmed a link between advanced age and heightened risk of recurrent UTIs in KTX. A recent prospective study highlighted UrS placement as a modifiable risk factor, emphasizing the need for careful consideration and antibiotic prophylaxis. Additionally, the type of stents played a crucial role, with external stents associated with a 1.69 times higher UTI risk. The challenge of determining optimal UrS removal timing further complicates posttransplant care, with insufficient evidence to guide practices. Summary The aging population of KTX recipients requires a personalized approach to effectively reduce and manage UTIs as one of the most important complications following KTX. Prophylactic stent implantation is successful in lowering ureteral complications, however, is associated with an increased incidence of UTIs. To reduce the increased risk of UTIs, the length of stent insertion requires strict supervision and maintenance.

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Asymptomatic Bacteriuria or Urinary Tract Infection? New and Old Biomarkers

Cited by 8 publications

References 52 publications

Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs

Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs

Evaluation of diagnostic accuracy of urine neutrophil gelatinase-associated lipocalin in patients with symptoms of urinary tract infections: a meta-analysis

Effect of increasing age and ureteral stent implantation on urinary tract infections after kidney transplantation – update of recent literature

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