The value of interleukin levels in the diagnosis of febrile urinary tract infections in children and adolescents; a systematic review and meta-analysis

Hosseini, Mostafa; Ahmadzadeh, Hooman; Toloui, Amirmohammad; Ahmadzadeh, Koohyar; Neishaboori, Arian Madani; Alavi, Seyedeh Niloufar Rafiei; Gubari, Mohammed Ibrahim Mohialdeen; Jones, Michael E.; Ataei, Fatemeh; Yousefifard, Mahmoud; Ataei, Nematollah

doi:10.1016/j.jpurol.2022.01.010

Cited by 7 publications

(11 citation statements)

References 31 publications

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“…The evidence for urinary IL-6 and IL-8 is mirrored in a recent systematic review of febrile children with UTI; urinary IL-6 had a pooled sensitivity of 77% (95% CI 69%-83%) and specificity of 87% (95% CI 86%-92%), and urinary IL-8 had a pooled sensitivity of 87% (95% CI 82%-91%) and specificity of 90% (95% CI 87%-93%). 63 Due to the nature and quality of evidence available there are some limitations to our findings. There was virtually no data on diagnostic performance, hence we were unable to perform quantitative analysis, either between biomarkers, or compared to dipstick or culture.…”

Section: Discussionmentioning

confidence: 92%

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What is the Diagnostic Accuracy of Novel Urine Biomarkers for Urinary Tract Infection?

et al. 2023

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Background: Urinary tract infection (UTI) affects half of women at least once in their lifetime. Current diagnosis involves urinary dipstick and urine culture, yet both methods have modest diagnostic accuracy, and cannot support decision-making in patient populations with high prevalence of asymptomatic bacteriuria, such as older adults. Detecting biomarkers of host response in the urine of hosts has the potential to improve diagnosis. Objectives: To synthesise the evidence of the diagnostic accuracy of novel biomarkers for UTI, and of their ability to differentiate UTI from asymptomatic bacteriuria. Design: A systematic review. Data Sources and Methods: We searched MEDLINE, EMBASE, CINAHL and Web of Science for studies of novel biomarkers for the diagnosis of UTI. We excluded studies assessing biomarkers included in urine dipsticks as these have been well described previously. We included studies of adult patients (≥16 years) with a suspected or confirmed urinary tract infection using microscopy and culture as the reference standard. We excluded studies using clinical signs and symptoms, or urine dipstick only as a reference standard. Quality appraisal was performed using QUADAS-2. We summarised our data using point estimates and data accuracy statistics. Results: We included 37 studies on 4009 adults measuring 66 biomarkers. Study quality was limited by case-control design and study size; only 4 included studies had a prospective cohort design. IL-6 and IL-8 were the most studied biomarkers. We found plausible evidence to suggest that IL-8, IL-6, GRO-a, sTNF-1, sTNF-2 and MCR may benefit from more rigorous evaluation of their potential diagnostic value for UTI. Conclusions: There is insufficient evidence to recommend the use of any novel biomarker for UTI diagnosis at present. Further evaluation of the more promising candidates, is needed before they can be recommended for clinical use.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

What is the Diagnostic Accuracy of Novel Urine Biomarkers for Urinary Tract Infection?

et al. 2023

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“…Accordingly, the role of different biomarkers in the study and prognosis of patients with urinary tract infection has been investigated in both serum and urine samples. [11][12][13][14][15][16][17][18][19][20][21]34 In our study, we evaluated the urinary concentrations of different biomarkers in 92 paediatric patients with DMSA-confirmed APN.…”

Section: Discussionmentioning

confidence: 99%

“…32 These biomarkers were selected according to previous literature and the technical possibility to be detected altogether in a multiplex analysis. [11][12][13][14][15][16][17][18][19][20] Pearson's chi-squared test was used for the statistical comparison of the categorical data. Correlations between quantitative variables were performed by Pearson or Spearman tests as appropriate.…”

Section: Key Notesmentioning

confidence: 99%

Role of dexamethasone in controlling the proinflammatory cytokine cascade in the first episode of paediatric acute pyelonephritis

Rius‐Gordillo,

Ferré,

González

et al. 2023

Acta Paediatrica

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AimFebrile urinary tract infection is a common bacterial infection in childhood. The kidney damage after acute pyelonephritis (APN) could be related to the stimulation of the proinflammatory response. We aimed to investigate the role of inflammatory cytokines and the effect of dexamethasone after a first episode of APN.MethodsSubanalysis of the DEXCAR RCT in which children with confirmed APN (1 month–14 years) were randomly assigned to receive a 3 days course of either intravenous dexamethasone or placebo. Urinary cytokine levels at diagnosis and after 72 h of treatment were measured.ResultsNinety‐two patients were recruited. Younger patients, males and those with abnormalities in the ultrasound study or vesicoureteral reflux showed higher values of urinary cytokines. Patients with severe APN had higher Tumour Necrosis Factor (TNF)α levels (81.0 ± 75.8 vs. 33.6 ± 48.5 pg/mg creatinine, p = 0.015). Both intervention groups showed similar basal clinical characteristics, including urinary cytokine levels. Treatment reduced urinary cytokine levels irrespective of dexamethasone administration. Neither the intervention group nor the urinary cytokine levels modulated the development of kidney scars.ConclusionBasal urinary cytokines were associated with age, abnormal ultrasound and vesicoureteral reflux. Patients with severe APN had higher TNFa urinary levels. Administration of dexamethasone in children with APN does not improve the control of the proinflammatory cytokine cascade.

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“…Furthermore, serum C-reactive protein and body temperature were also not related to urinary IL-6 levels [ 207 ]. The prognostic value of urinary IL-6 levels was substantiated in a recent meta-analysis that identified urinary IL-6 concentrations as appropriate to detect febrile urinary tract infections in children and to distinguish them from other febrile conditions [ 208 ] ( Figure 5 ). In contrast to these findings, an earlier study could not detect significant differences in urinary IL-6 levels when comparing nonbacteremic and bacteremic febrile patients.…”

Section: Adipokines In Urine and Fecesmentioning

confidence: 99%

Fecal and Urinary Adipokines as Disease Biomarkers

et al. 2023

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The use of biomarkers is of great clinical value for the diagnosis and prognosis of disease and the assessment of treatment efficacy. In this context, adipokines secreted from adipose tissue are of interest, as their elevated circulating levels are associated with a range of metabolic dysfunctions, inflammation, renal and hepatic diseases and cancers. In addition to serum, adipokines can also be detected in the urine and feces, and current experimental evidence on the analysis of fecal and urinary adipokine levels points to their potential as disease biomarkers. This includes increased urinary adiponectin, lipocalin-2, leptin and interleukin-6 (IL-6) levels in renal diseases and an association of elevated urinary chemerin as well as urinary and fecal lipocalin-2 levels with active inflammatory bowel diseases. Urinary IL-6 levels are also upregulated in rheumatoid arthritis and may become an early marker for kidney transplant rejection, while fecal IL-6 levels are increased in decompensated liver cirrhosis and acute gastroenteritis. In addition, galectin-3 levels in urine and stool may emerge as a biomarker for several cancers. With the analysis of urine and feces from patients being cost-efficient and non-invasive, the identification and utilization of adipokine levels as urinary and fecal biomarkers could become a great advantage for disease diagnosis and predicting treatment outcomes. This review article highlights data on the abundance of selected adipokines in urine and feces, underscoring their potential to serve as diagnostic and prognostic biomarkers.

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The value of interleukin levels in the diagnosis of febrile urinary tract infections in children and adolescents; a systematic review and meta-analysis

Cited by 7 publications

References 31 publications

What is the Diagnostic Accuracy of Novel Urine Biomarkers for Urinary Tract Infection?

What is the Diagnostic Accuracy of Novel Urine Biomarkers for Urinary Tract Infection?

Role of dexamethasone in controlling the proinflammatory cytokine cascade in the first episode of paediatric acute pyelonephritis

Fecal and Urinary Adipokines as Disease Biomarkers

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