Factors limiting usefulness of serum and urinary NGAL as a marker of acute kidney injury in preterm newborns

Suchojad, Anna; Tarko, Anna; Smertka, Mike; Majcherczyk, Małgorzata; Brzozowska, Aniceta; Wróblewska, Jolanta; Maruniak‐Chudek, Iwona

doi:10.3109/0886022x.2014.996109

Cited by 27 publications

(19 citation statements)

References 30 publications

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“…17 Furthermore, according to Askenazi et al, 10 uNGAL/mgCr also decreases with increasing GA, and there are detailed reports where uNGAL levels declined by 23.1% 10 or by 17.8% 17 for each week of increasing GA. However, there are also researchers who found no association between uNGAL and GA 23,25,30,39 and those who report no correlation with BW, 23,30,39 or PNA. 23,27,38 However, Huynh et al 17 demonstrated that uNGAL levels declined by 1.33% for each day of PNA.…”

Section: Discussionmentioning

confidence: 98%

eGFR values and selected renal urine biomarkers in preterm neonates with uncomplicated clinical course

Miklaszewska¹,

Korohoda²,

Drożdż³

et al. 2019

Adv Clin Exp Med

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Background. Diagnosing acute kidney injury (AKI) in preterm newborns, who are particularly susceptible to renal damage, is a serious challenge as there is no definite consensus about the diagnostic criteria. Objectives. The objective of this study was to measure the values for selected urinary biomarkers and estimated glomerular filtration rate (eGFR) among a population of preterm infants with uncomplicated clinical course as well as to determine whether these markers depend on birth weight (BW), gestational age (GA), postnatal age (PNA), or gender. Material and methods. The prospective study was carried out in neonatal intensive care unit (NICU). The evaluation included 57 children that were divided into 3 categories according to BW: low birth weight (LBW)-1501-2500 g (22 infants); very low birth weight (VLBW)-1000-1500 g (25 infants); and extremely low birth weight (ELBW)-750-999 g (10 infants). Urine samples were collected daily between the 4 th and 28 th day of life for measurements of creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and human kidney injury molecule 1 (hKIM1). Results. The values of the 3 urine tubular biomarkers, serum creatinine and eGFR were taken in substantially healthy preterm infants with normal kidney function at 4 time intervals during the neonatal period. Their correlations were determined and a multivariable regression analysis was carried out with respect to BW, GA, PNA, and gender. Trends of the studied markers in terms of PNA and BW were also assessed with the Jonckheere-Terpstra test. Conclusions. Glomerular and tubular function in preterm neonates during the 1 st month of life is significantly influenced by BW, GA, PNA, and gender.

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Section: Discussionmentioning

confidence: 98%

eGFR values and selected renal urine biomarkers in preterm neonates with uncomplicated clinical course

Miklaszewska¹,

Korohoda²,

Drożdż³

et al. 2019

Adv Clin Exp Med

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“…Pertinently to PE, it is also well established as an early biomarker of acute kidney injury (AKI) (838–841). However, it is not a specific biomarker for AKI vs. sepsis (839, 842–850) and its origin in sepsis differs (851, 852). Of course, it can be the sepsis that leads to the AKI (853, 854).…”

Section: Proteomic and Similar Biomarkers – Circulating And Placentalmentioning

confidence: 99%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “preeclampsia” that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.

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“…Prior literature has shown that in premature infants without AKI, urine proteins will be highest among those with the lowest GA, probably because of the passive loss of proteins in the context of immature tubular function (6)(7)(8). Previously, we (7) and others (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) have published data on the ability of urine biomarkers to predict AKI in neonates; however, these studies are limited by the size of the cohort or the use of nested case-control methods, with most of these studies evaluating only one biomarker. In addition, previous studies were subject to risk of misclassification bias, given that many infants had only a few SCr levels measured to determine AKI.…”

Section: Introductionmentioning

confidence: 99%

Acute Kidney Injury Urine Biomarkers in Very Low-Birth-Weight Infants

Askenazi

Koralkar

Patil

et al. 2016

CJASN

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Background and objectives Serum creatinine (SCr)-based AKI definitions have important limitations, particularly in very low-birth-weight (VLBW) neonates. Urine biomarkers may improve our ability to detect kidney damage. We assessed the association between 14 different urine biomarkers and AKI in VLBW infants.Design, setting, participants, & measurements We performed a prospective cohort study on 113 VLBW infants (weight #1200 g or ,31 weeks' gestation) admitted to a regional neonatal intensive care unit at the University of Alabama at Birmingham between February 2012 and June 2013. SCr was measured on postnatal days 1, 2, 3, and 4 and was combined with clinically measured SCr to determine AKI according to Kidney Disease Improving Global Outcomes AKI definition (increase in SCr $0.3 mg/dl or $50% increase from previous lowest value). Urine was collected on the first 4 days (average number of urine collections, 3; range, 1-4). The maximum urine biomarkers and urine biomarker/creatinine levels were calculated for 12 urine biomarkers, and the minimum urine biomarker and biomarker/creatinine levels were assessed for two urine biomarkers. We compared these values between infants with and those without AKI. Ideal cutoffs, area under the receiver-operating characteristic curve , and area under the curve adjusted for gestational age were calculated.Results Cumulative incidence of AKI during the first 2 postnatal weeks was 28 of 113 (25%). Infants with AKI had higher maximum levels of urine cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, clusterin, and a glutathione S-transferase (2.0, 1.8, 1.7, 1.7, and 3.7 times higher, respectively) than infants without AKI. In addition, infants with AKI had lower minimum levels of epithelial growth factor and uromodulin than those without AKI (1.4 and 1.6 times lower, respectively). Most but not all participants had their maximum (or minimum) biomarker values preceding AKI. These associations remained after adjustment for gestational age.Conclusions Urine biomarkers measured in the first 4 days of life are associated with AKI during the first postnatal weeks. Further evaluations are necessary to determine whether these biomarkers can predict important clinical outcomes. In addition, intervention studies that use biomarkers to stratify enrollment groups are needed before bedside evaluations can be incorporated into care.

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Factors limiting usefulness of serum and urinary NGAL as a marker of acute kidney injury in preterm newborns

Cited by 27 publications

References 30 publications

eGFR values and selected renal urine biomarkers in preterm neonates with uncomplicated clinical course

eGFR values and selected renal urine biomarkers in preterm neonates with uncomplicated clinical course

A Dormant Microbial Component in the Development of Preeclampsia

Acute Kidney Injury Urine Biomarkers in Very Low-Birth-Weight Infants

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