Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action): Reduction of Nephrotoxic Medication-Associated Acute Kidney Injury in the Neonatal Intensive Care Unit

Stoops, Christine; Stone, Sadie B.; Evans, Emily; Dill, Lynn; Henderson, Traci; Griffin, Russell; Goldstein, Stuart L.; Coghill, Carl; Askenazi, David

doi:10.1016/j.jpeds.2019.08.046

Cited by 110 publications

(96 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…14 The "baby NINJA" study reported positive associations between the number of nephrotoxic agents administered in the NICU and the increase risk of AKI in very preterm infants. 15 Nonetheless, bivariate analysis of several factors such as nephrotoxic drug exposure, sepsis, gestational age and birth weight showed no association with glomerulotubular injury at the age of 21 days in our participants. However, it is also important to mention that this study was not designed to analyse those factors, and the number of participants may have affected the results of the statistical analysis.…”

Section: Discussioncontrasting

confidence: 63%

Does High Protein Intake Cause Glomerular Injury in Very Preterm Neonates?

Puspitasari

Trihono

Wahidiyat

2020

Preprint

View full text Add to dashboard Cite

Background: Very preterm birth rate was 10.8% of all preterm in Asia. Early aggressive nutritional strategies in very preterm neonates is important for catching up growth; however, preterm kidneys have fewer, immature functional nephrons. Studies have showed that high protein intake induces nephron hypertrophy, proteinuria, and glomerular sclerosis through single nephron glomerular hyperfiltration (SNGHF), which leads to glomerulotubular injury. Aim: to analyse the correlation between protein intake and glomerulotubular injury in very preterm neonates. Method: A prospective cohort study was conducted in neonatal units of two hospitals in Jakarta. Urine samples were taken three times at post-natal ages 0-48 hours (T1), 72 hours (T2), and 21 days (T3) for determining the urinary neutrophil gelatinase-associated lipocalin to creatinine (uNGAL/Cr) ratio. Protein intake were given in accordance with local guideline while considering the clinical condition of participants. Protein levels from formula milk were recorded daily from 14-21 days of age, while breastmilk protein was measured twice by using a human milk analyser. Urinary NGAL (uNGAL) was tested with an ELISA. Glomerulotubular injury was defined as a uNGAL/Cr ratio ≥1 SD (22.74 ng/mg) at post-natal age 21 days. High protein intake was defined as average protein intake ≥ 3 g/kg/day.Results: Fifty-nine very preterm neonates were recruited, of which 39 completed the study. Glomerulotubular injury was found in 9 of 39 participants (23%). The proportion of glomerulotubular injury in very preterm neonates who had received high protein intake vs low protein intake was 5 of 29 vs 4 of 10 participants, respectively. The median of uNGAL/Cr ratio was not significantly different in the high vs low protein intake group (3.54 (range: 0.69-89.16) ng/mg vs (6.88 (range: 0.32-66.64)) ng/mg, respectively. The uNGAL/C ratio was not correlated with protein intake. However, it was inversely correlated with gestational age and birth weight.Conclusions: The proportion of glomerulotubular injury in very preterm neonates given high protein diet was 5 of 29. The uNGAL/Cr ratio was increased at the post-natal age of 72 hours and decreased in 21 days in both high and low protein intake groups. High protein intake was not correlated with glomerulotubular injury.

show abstract

Section: Discussioncontrasting

confidence: 63%

Does High Protein Intake Cause Glomerular Injury in Very Preterm Neonates?

Puspitasari

Trihono

Wahidiyat

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…During these events, a daily S cr was obtained until 2 days after exposure or after end of AKI. Within this framework, there was a reduction in exposure (16.4 to 9.6/1,000 patient days), a reduction in drug-associated AKI (30.9 to 11%), and in AKI intensity (9.1 to 2.9/100 susceptible patient days) ( 60 ). Implementation of AKI guidelines in a single NICU resulted in improvements in recognition, diagnosis, and subsequent follow-up of AKI ( 61 ).…”

Section: Renal Precision As Crucial Part Of Contemporary Neonatal Prementioning

confidence: 99%

Renal Precision Medicine in Neonates and Acute Kidney Injury: How to Convert a Cloud of Creatinine Observations to Support Clinical Decisions

et al. 2020

View full text Add to dashboard Cite

Renal precision medicine in neonates is useful to support decision making on pharmacotherapy, signal detection of adverse (drug) events, and individual prediction of short- and long-term prognosis. To estimate kidney function or glomerular filtration rate (GFR), the most commonly measured and readily accessible biomarker is serum creatinine (S cr ). However, there is extensive variability in S cr observations and GFR estimates within the neonatal population, because of developmental physiology and superimposed pathology. Furthermore, assay related differences still matter for S cr , but also exist for Cystatin C. Observations in extreme low birth weight (ELBW) and term asphyxiated neonates will illustrate how renal precision medicine contributes to neonatal precision medicine. When the Kidney Disease Improving Global Outcome (KDIGO) definition of acute kidney injury (AKI) is used, this results in an incidence up to 50% in ELBW neonates, associated with increased mortality and morbidity. However, urine output criteria needed adaptations to broader time intervals or weight trends, while S cr and its trends do not provide sufficient detail on kidney function between ELBW neonates. Instead, we suggest to use assay-specific centile S cr values to better describe postnatal trends and have illustrated its relevance by quantifying an adverse drug event (ibuprofen) and by explaining individual amikacin clearance. Term asphyxiated neonates also commonly display AKI. While oliguria is a specific AKI indicator, the majority of term asphyxiated cases are non-oliguric. Asphyxia results in a clinical significant—commonly transient—mean GFR decrease (−50%) with a lower renal drug elimination. But there is still major (unexplained) inter-individual variability in GFR and subsequent renal drug elimination between these asphyxiated neonates. Recently, the Baby-NINJA (nephrotoxic injury negated by just-in-time action) study provided evidence on the concept that a focus on nephrotoxic injury negation has a significant impact on AKI incidence and severity. It is hereby important to realize that follow-up should not be discontinued at discharge, as there are concerns about long-term renal outcome. These illustrations suggest that integration of renal (patho)physiology into neonatal precision medicine are an important tool to improve contemporary neonatal care, not only for the short-term but also with a positive health impact throughout life.

show abstract

“…Our findings further expand recent work focused on reducing nephrotoxin associated acute kidney injury through improved surveillance and monitoring, further supporting the importance of integration of nephrology providers into intensive care units. 19 While such “Neonatal Nephrology” integration is both time and resource intensive, we show that it is associated with decreased AKI incidence, improved recognition, and increased follow-up for neonates with kidney injury and it may have the potential to improve care. Despite an increase in identification of AKI and referral for AKI follow-up, the uptake of these interventions remained below expected interval improvement with clinical practice changes.…”

Section: Discussionmentioning

confidence: 82%

“…Similar to other previous studies assessing nephrotoxin exposure in neonates, neonates who received 3 or more concurrent nephrotoxic medications during their admission were considered to have high nephrotoxin exposure. 19 We did not consider a prolonged single nephrotoxin exposure as high nephrotoxin exposure. 19 …”

Section: Methodsmentioning

confidence: 99%