Neutrophil Gelatinase-Associated Lipocalin: A Biomarker for Early Diagnosis of Urinary Tract Infections in Infants

Urinary biomarkers, such as albumin and other markers of kidney injury, are frequently reported as a normalized ratio to urinary creatinine (UCr) concentration [UCr] to control for variations in urine flow rate. The implicit assumption is that UCr excretion is constant across and within individuals, such that changes in the ratio will reflect changes in biomarker excretion. Using computer simulations of creatinine kinetics, we found that normalized levels of a biomarker reflecting tubular injury can be influenced by dynamic changes in the UCr excretion rate when the glomerular filtration rate changes. Actual timed urine collections from hospitalized patients with changing glomerular filtration rates and/or critical illness exhibited variability in UCr excretion rates across and within individuals. Normalization by [UCr] may, therefore, result in an underestimation or overestimation of the biomarker excretion rate depending on the clinical context. Lower creatinine excretion in the setting of acute kidney injury or poor renal allograft function may amplify a tubular injury biomarker signal, thereby increasing its clinical utility. The variability of creatinine excretion, however, will complicate the determination of a threshold value for normalized biomarkers of acute or chronic kidney disease, including albumin. Thus, we suggest that the most accurate method to quantify biomarkers requires the collection of timed urine specimens to estimate the actual excretion rate, provided that the biomarker is stable over the period of collection. This ideal must be balanced, however, against practical considerations.

To revise the American Academy of Pediatrics practice parameter regarding the diagnosis and management of initial urinary tract infections (UTIs) in febrile infants and young children. Analysis of the medical literature published since the last version of the guideline was supplemented by analysis of data provided by authors of recent publications. The strength of evidence supporting each recommendation and the strength of the recommendation were assessed and graded. Diagnosis is made on the basis of the presence of both pyuria and at least 50,000 colonies per mL of a single uropathogenic organism in an appropriately collected specimen of urine. After 7 to 14 days of antimicrobial treatment, close clinical follow-up monitoring should be maintained to permit prompt diagnosis and treatment of recurrent infections. Ultrasonography of the kidneys and bladder should be performed to detect anatomic abnormalities. Data from the most recent 6 studies do not support the use of antimicrobial prophylaxis to prevent febrile recurrent UTI in infants without vesicoureteral reflux (VUR) or with grade I to IV VUR. Therefore, a voiding cystourethrography (VCUG) is not recommended routinely after the first UTI; VCUG is indicated if renal and bladder ultrasonography reveals hydronephrosis, scarring, or other findings that would suggest either high-grade VUR or obstructive uropathy and in other atypical or complex clinical circumstances. VCUG should also be performed if there is a recurrence of a febrile UTI. The recommendations in this guideline do not indicate an exclusive course of treatment or serve as a standard of care; variations may be appropriate. Recommendations about antimicrobial prophylaxis and implications for performance of VCUG are based on currently available evidence. As with all American Academy of Pediatrics clinical guidelines, the recommendations will be reviewed routinely and incorporate new evidence, such as data from the Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study. Changes in this revision include criteria for the diagnosis of UTI and recommendations for imaging.

In 30% of children with urinary tract anomalies, urinary tract infection (UTI) can be the first sign. Failure to identify patients at risk can result in damage to the upper urinary tract.