Neutrophil gelatinase-associated lipocalin for urinary tract infection and pyelonephritis: a systematic review.

BACKGROUND: The sensitivity and specificity of the leukocyte esterase test are relatively low for a screening test for urinary tract infection (UTI). More accurate tests could reduce both overtreatment and missed cases. This study aimed to determine whether neutrophil gelatinase-associated lipocalin (NGAL) can replace leukocyte esterase in the diagnosis of UTI and/or whether NGAL accurately identifies children with acute pyelonephritis. METHODS: Data sources-MEDLINE and EMBASE. We only considered published studies that evaluated the results of an index test (NGAL) against the results of urine culture (for UTI) or against the results of dimercaptosuccinic acid (for acute pyelonephritis) in children aged 0 to 18 years. Two authors independently applied the selection criteria to all citations and independently extracted the data. RESULTS: A total of 12 studies met our inclusion criteria. Four studies (920 children) included data on NGAL for UTI; eight studies (580 children) included data on NGAL for pyelonephritis. We did not pool accuracy values because the included studies used different cutoff values. For the diagnosis of UTI, urinary NGAL appeared to have better accuracy than the leukocyte esterase test in all included studies. For the diagnosis of pyelonephritis, neither plasma NGAL nor urinary NGAL had high sensitivity and/or specificity. The number of studies was the main limitation of this systematic review. CONCLUSIONS: Urinary NGAL appears promising for the diagnosis of UTI; however, larger studies are needed to validate this marker as a replacement for leukocyte esterase. The use of NGAL for diagnosing acute pyelonephritis requires further study.

Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury.

BACKGROUND: Damage to the renal microvasculature is a hallmark of renal ischemia-reperfusion injury (IRI)-mediated AKI. The miR-17∼92 miRNA cluster (encoding miR-17, -18a, -19a, -20a, -19b-1, and -92a-1) regulates angiogenesis in multiple settings, but no definitive role in renal endothelium during AKI pathogenesis has been established. METHODS: Antibodies bound to magnetic beads were utilized to selectively enrich for renal endothelial cells from mice. Endothelial-specific miR-17∼92 knockout (miR-17∼92endo-/- ) mice were generated and given renal IRI. Mice were monitored for the development of AKI using serum chemistries and histology and for renal blood flow using magnetic resonance imaging (MRI) and laser Doppler imaging. Mice were treated with miRNA mimics during renal IRI, and therapeutic efficacies were evaluated. RESULTS: miR-17, -18a, -20a, -19b, and pri-miR-17∼92 are dynamically regulated in renal endothelial cells after renal IRI. miR-17∼92endo-/- exacerbates renal IRI in male and female mice. Specifically, miR-17∼92endo-/- promotes renal tubular injury, reduces renal blood flow, promotes microvascular rarefaction, increases renal oxidative stress, and promotes macrophage infiltration to injured kidneys. The potent antiangiogenic factor thrombospondin 1 (TSP1) is highly expressed in renal endothelium in miR-17∼92endo-/- after renal IRI and is a target of miR-18a and miR-19a/b. miR-17∼92 is critical in the angiogenic response after renal IRI, which treatment with miR-18a and miR-19b mimics can mitigate. CONCLUSIONS: These data suggest that endothelial-derived miR-17∼92 stimulates a reparative response in damaged renal vasculature during renal IRI by regulating angiogenic pathways.

Procalcitonin, C-reactive protein, and erythrocyte sedimentation rate for the diagnosis of acute pyelonephritis in children.

BACKGROUND: In children with urinary tract infection (UTI), only those with pyelonephritis (and not cystitis) are at risk for developing long-term renal sequelae. If non-invasive biomarkers could accurately differentiate children with cystitis from children with pyelonephritis, treatment and follow-up could potentially be individualized. This is an update of a review first published in 2015. OBJECTIVES: The objectives of this review were to 1) determine whether procalcitonin (PCT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) can replace the acute DMSA scan in the diagnostic evaluation of children with UTI; 2) assess the influence of patient and study characteristics on the diagnostic accuracy of these tests, and 3) compare the performance of the three tests to each other. SEARCH METHODS: We searched MEDLINE, EMBASE, DARE, Web of Science, and BIOSIS Previews through to 17th December 2019 for this review. The reference lists of all included articles and relevant systematic reviews were searched to identify additional studies not found through the electronic search. SELECTION CRITERIA: We only considered published studies that evaluated the results of an index test (PCT, CRP, ESR) against the results of an acute-phase 99Tc-dimercaptosuccinic acid (DMSA) scan (conducted within 30 days of the UTI) in children aged 0 to 18 years with a culture-confirmed episode of UTI. The following cut-off values were used for the primary analysis: 0.5 ng/mL for procalcitonin, 20 mg/L for CRP and 30 mm/hour for ESR. DATA COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate pooled random-effects pooled sensitivity and specificity values. MAIN RESULTS: A total of 36 studies met our inclusion criteria. Twenty-five studies provided data for the primary analysis: 12 studies (1000 children) included data on PCT, 16 studies (1895 children) included data on CRP, and eight studies (1910 children) included data on ESR (some studies had data on more than one test). The summary sensitivity estimates (95% CI) for the PCT, CRP, ESR tests at the aforementioned cut-offs were 0.81 (0.67 to 0.90), 0.93 (0.86 to 0.96), and 0.83 (0.71 to 0.91), respectively. The summary specificity values for PCT, CRP, and ESR tests at these cut-offs were 0.76 (0.66 to 0.84), 0.37 (0.24 to 0.53), and 0.57 (0.41 to 0.72), respectively. AUTHORS' CONCLUSIONS: The ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis. A low CRP value (< 20 mg/L) appears to be somewhat useful in ruling out pyelonephritis (decreasing the probability of pyelonephritis to < 20%), but unexplained heterogeneity in the data prevents us from making recommendations at this time. The procalcitonin test seems better suited for ruling in pyelonephritis, but the limited number of studies and the marked heterogeneity between studies prevents us from reaching definitive conclusions. Thus, at present, we do not find any compelling evidence to recommend the routine use of any of these tests in clinical practice.

Adverse Events of Antibiotics Used to Treat Acute Otitis Media in Children: A Systematic Meta-Analysis.

OBJECTIVE: To characterize the incidence of adverse events (AEs) associated with antibiotics used to treat acute otitis media in children. STUDY DESIGN: We searched MEDLINE for studies conducted between January 1, 1966, and August 25, 2018. Two authors independently assessed potential studies and extracted the data. We included published randomized controlled trials, cross-sectional studies, and cohort studies that evaluated the incidence of diarrhea, generalized rash, diaper rash, and candidal diaper dermatitis associated with the use of amoxicillin, amoxicillin/clavulanate, azithromycin, cefdinir, and placebo in children with acute otitis media. RESULTS: We included 82 studies in the meta-analysis. The incidence of diarrhea, listed from lowest to highest, was azithromycin (2.2%), placebo (6.9%), low-dose amoxicillin (8.7%), cefdinir (13.0%), high-dose amoxicillin (13.8%), and high-dose amoxicillin/clavulanate (18.9%). The incidence of generalized rash, listed from lowest to highest, was azithromycin (1.4%), placebo (2.3%), low-dose amoxicillin (2.9%), high-dose amoxicillin/clavulanate (4.9%), and high-dose amoxicillin (6.5%). In studies of low-dose amoxicillin, we found a higher incidence of diarrhea in studies that used daily diaries to collect information about diarrhea and a lower incidence of generalized rash in studies that reported only rashes judged to be secondary to antibiotic use. CONCLUSIONS: The incidence of AEs varies widely depending on which antibiotic is used and how the information on AEs was collected or reported. The AEs rates reported here may be helpful to clinicians when choosing an antibiotic to treat acute otitis media.