A pilot study of urinary fibroblast growth factor-2 and epithelial growth factor as potential biomarkers of acute kidney injury in critically ill children

Wai, Kitman; Soler-García, Ángel A.; Perazzo, Sofia; Mattison, Parnell C.; Ray, Patricio E.

doi:10.1007/s00467-013-2543-3

Cited by 19 publications

(28 citation statements)

References 57 publications

(73 reference statements)

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“…In the kidney, NGAL is synthesized mainly by distal tubular epithelial cells [34] and is considered to be a sensitive biomarker of AKI in critically ill children and infants [28, 35–38]. However, we found that the urinary levels of NGAL did not offer early sensitivity and/or improved specificity for the identification of AKI in term newborns with HIE during the first days of life.…”

Section: Discussionmentioning

confidence: 68%

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A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy

2016

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Background Current definitions of acute kidney injury (AKI) are not sufficiently sensitive to identify all newborns with AKI during the first week of life. Methods To determine whether the rate of decline of serum creatinine (SCr) during the first week of life can be used to identify newborns with AKI, we reviewed the medical records of 106 term neonates at risk of AKI who were treated with hypothermia for hypoxic ischemic encephalopathy (HIE). Results Of the newborns enrolled in the study, 69 % showed a normal rate of decline of SCr to ≥50 % and/or reached SCr levels of ≤0.6 mg/dl before the 7th day of life, and therefore had an excellent clinical outcome (control group). Thirteen newborns with HIE (12 %) developed AKI according to an established neonatal definition (AKI–KIDGO group), and an additional 20 newborns (19 %) showed a rate of decline of SCr of <33, <40, and <46 % from birth to days 3, 5, or 7 of life, respectively (delayed rise in estimated SCr clearance group). Compared to the control group, newborns in the other two groups required more days of mechanical ventilation and vasopressor drugs and had higher gentamicin levels, more fluid overload, lower urinary epidermal growth factor levels, and a prolonged length of stay. Conclusions The rate of decline of SCr provides a sensitive approach to identify term newborns with AKI during the first week of life.

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Section: Discussionmentioning

confidence: 68%

“…The SCr measurements done in control samples from healthy newborns were within the normal range. The urinary levels of neutrophil associated gelatinase lipocalin (NGAL) and epidermal growth factor (EGF) were measured using enzyme-linked-immunoabsorbent assay as described in detailed in our previous studies [26, 28]. …”

Section: Methodsmentioning

confidence: 99%

A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy

2016

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“…Another explanation may lie in the lower severity of illness in the Zappitelli cohort, as reflected by a median PRISM II score of 19 (IQR, 12) [ 28 ] for the renal failure group compared with 48.9 (IQR, 25.5 to 77.1) in our patients with AKI. Furthermore, as uNGAL and KIM-1 levels in premature infants and young children generally are higher than healthy infants and young children, the younger age of our subjects might form another explanation [ 29 , 37 , 38 ]. Last, Zappitelli and colleagues used other biomarker kits [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…They found a good diagnostic marker for development of AKI and persistent AKI for ≥48 hours, but not for AKI if uNGAL had been measured after a rise in SCr [ 28 ]. In later studies focused on cutoff points for AKI prediction specifically in PICU patients, researchers evaluated biomarker combinations and even suggested uNGAL as a predictor of mortality [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: a prospective cohort study

et al. 2015

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IntroductionChildren admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although serum creatinine (SCr) levels are used in clinical practice, they are insensitive for early diagnosis of AKI. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are novel AKI biomarkers whose performance in pediatric ICU patients is largely unknown. In this study, we aimed to characterize uNGAL and KIM-1 patterns in children following ICU admission and to assess their properties in relation to identifying children at risk for AKI development.MethodsFrom June 2010 until January 2014, we conducted a prospective observational cohort study of term-born children ages 1 day to 1 year on mechanical ventilation. Blood and urine samples were obtained every 6 to 12 hours up to 72 hours post-admission. Blood samples were assayed for SCr, and urine samples were assayed for uNGAL and KIM-1. The RIFLE (risk, injury, failure, loss, end-stage renal disease) classification as 150%, 200% or 300% of median SCr reference values was used to define AKI.ResultsA total of 100 children were included (80 survived). Their median age at admission was 27.7 days (interquartile range (IQR), 1.5 to 85.5). The median duration of mechanical ventilation was 5.8 days (IQR, 3.1 to 11.4). Thirty-five patients had evidence of AKI within the first 48 hours post-admission, of whom 24 (69%) already had AKI when they entered the ICU. uNGAL and KIM-1 concentrations in AKI peaked between 6 to 12 hours and between 12 to 24 hours post-admission, respectively. The maximal area under the receiver operating characteristic curve (AUC) for uNGAL was 0.815 (95% confidence interval (CI), 0.685 to 0.945, P <0.001) at 0 to 6 hours post-admission. The discriminative ability of KIM-1 was moderate, with a largest AUC of 0.737 (95% CI, 0.628 to 0.847; P <0.001) at 12 to 24 hours post-admission. At the optimal cutoff point (126 ng/ml), uNGAL concentration predicted AKI development correctly in 16 (84%) of 19 children, up to 24 hours before a rise in SCr became apparent.ConclusionsLevels of uNGAL and KIM-1 increase in patients with AKI following ICU admission and peak at 6 to 12 hours and 12 to 24 hours post-admission, respectively. uNGAL seems to be a reliable marker for identifying children who will develop AKI 24 hours later.

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“…Intense research efforts using animal models have shed light on the pathophysiology of AKI. It has been reported that the expression of Fibroblast growth factors (FGFs) and their receptors (FGFRs) are increased in the context of AKI (Wai et al, 2013;Tan et al, 2017). Furthermore, AKI is more severe upon FGFR deficiency or blockade of its signalling (Villanueva et al, 2008;Xu and Dai, 2017).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factors in the Management of Acute Kidney Injury Following Ischemia-Reperfusion

et al. 2020

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Ischemia-reperfusion injury (IRI), which is triggered by a transient reduction or cessation of blood flow followed by reperfusion, is a significant cause of acute kidney injury (AKI). IRI can lead to acute cell death, tissue injury, and even permanent organ dysfunction. In the clinic, IRI contributes to a higher morbidity and mortality and is associated with an unfavorable prognosis in AKI patients. Unfortunately, effective clinical drugs to protect patients against the imminent risk of renal IRI or treat already existing AKI are still lacking. Fibroblast growth factors (FGFs) are important regulators of key biological and pathological processes, such as embryonic development, metabolic homeostasis and tumorigenesis through the regulation of cell differentiation, migration, proliferation and survival. Accumulating evidence suggests that altered expression of endogenous FGFs is associated with IRI and could be instrumental in mediating the repair process. Therefore, FGFs have been proposed as potential biomarkers in the clinic. More importantly, exogenous FGF ligands have been reported to protect against renal IRI and display promising features for therapy. In this review, we summarize the evidence and mechanisms of AKI following IRI with a focus on the therapeutic capacity of several members of the FGF family to treat AKI after IRI.

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A pilot study of urinary fibroblast growth factor-2 and epithelial growth factor as potential biomarkers of acute kidney injury in critically ill children

Cited by 19 publications

References 57 publications

A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy

A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy

Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: a prospective cohort study

Fibroblast Growth Factors in the Management of Acute Kidney Injury Following Ischemia-Reperfusion

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