Evidence map›Paper›PMID 40172287›Full record

Trial reportPediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies2025

Time Course of Kidney Injury Biomarkers in Children With Septic Shock: Nested Cohort Study Within the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis Trial.

Scott L Weiss, Julie C Fitzgerald, Benjamin L Laskin, Ruchi Singh, Amanda S Artis, Ananya Vohra, Elena Tsemberis, Emem Kierian, Kristen C Lau, Atzael B Campos and 14 more

Erratum issued Registry-linked trialAbstract readMulticenter StudyPragmatic Clinical Trial
In one paragraph

Trial report in Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04102371 (Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04102371 phase3completednot on this map

Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis

TypeinterventionalSponsorChildren's Hospital of PhiladelphiaRan2020 to 2026Enrolled9,041ConditionsShock, SepticArmsLactated Ringer, Normal Saline, Plasma-lyte
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. PRoMPTing Practice Change in Pediatric Sepsis: Is There a Role for Acute Kidney Injury Biomarkers in Early Fluid Resuscitation?Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2025
    Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Scott L WeissDivision of Critical Care, Department of Pediatrics, Nemours Children's Hospital, Wilmington, DE.ORCID 0000-0002-7040-3281
Julie C FitzgeraldDepartment of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Benjamin L LaskinDepartment of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Ruchi SinghDepartment of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Amanda S ArtisDepartment of Biomedical and Health Informatics, Data Science and Biostatistics Unit, Children's Hospital of Philadelphia, Philadelphia, PA.
Ananya VohraDepartment of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Elena TsemberisDepartment of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Emem KierianDepartment of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Kristen C LauDepartment of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Atzael B CamposDepartment of Biomedical and Health Informatics, Clinical Reporting Unit, Children's Hospital of Philadelphia, Philadelphia, PA.
Christopher HickeyDepartment of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Katie L HayesChildren's Hospital of Philadelphia Pediatric Sepsis Program, Philadelphia, PA.
Daniel SingletonDepartment of Biomedical and Health Informatics, Clinical Reporting Unit, Children's Hospital of Philadelphia, Philadelphia, PA.
Elliot LongDepartment of Emergency Medicine, The Royal Children's Hospital, Melbourne, VIC, Australia.
Franz E BablDepartment of Emergency Medicine, The Royal Children's Hospital, Melbourne, VIC, Australia.
Stuart R DalzielDepartments of Surgery and Pediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand.
Graham C ThompsonDepartments of Pediatrics and Emergency Medicine, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary. AB, Canada.
Stephen B FreedmanSections of Pediatric Emergency Medicine and Gastroenterology, Departments of Pediatrics and Emergency Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Michelle EckerleDivision of Emergency Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Robert W HickeyDivision of Pediatric Emergency Medicine, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA.
Jing HuangDepartment of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Nathan KuppermannDepartments of Pediatrics and Emergency Medicine, George Washington School of Medicine and Health Sciences, Washington, DC.
Fran BalamuthChildren's Hospital of Philadelphia Pediatric Sepsis Program, Philadelphia, PA.
Pragmatic Pediatric Trial of Balanced vs. Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the Pediatric Emergency Care Applied Research Network (PECARN), Pediatric Emergency Research Canada (PERC), and Pediatric Research in Emergency Departments International Collaborative (PREDICT) Networks

Funding

Research Project Core 2P50DK114786 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI Razzaghi Hanieh · 2017 to 2026
$9.6M
PROMPT BOLUS admin supplementR01HD101528 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI BALAMUTH, FRANCES B, WEISS, SCOTT L · 2020 to 2024
$4.8M
Finding Appropriate Subtypes in a Trial of Balanced versus nOrmaL Saline FlUid in SepsisR01GM145698 · NIGMS · CHILDREN'S HOSP OF PHILADELPHIA · PI YEHYA, NADIR · 2022 to 2025
$2.6M
Pediatric septic acute kidney injury: personalizing antibiotic dosing through understanding acute kidney injury risk factors and biomarker profilesK23DK119463 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI FITZGERALD, JULIE C. HOLLOWS · 2020 to 2024
$810k
NICHD NIH HHS R01 HD101528NIDDK NIH HHS K23 DK119463NIDDK NIH HHS P50 DK114786NIGMS NIH HHS R01 GM145698
6 · The paper itself

Abstract

objectiveSevere acute kidney injury (AKI) portends poor outcomes in pediatric sepsis. We evaluated the trajectory and prognostic utility of AKI biomarkers in pediatric septic shock using a subset of participants in the ongoing Pragmatic Pediatric Trial of Balanced vs. Normal Saline Fluid in Sepsis (PRoMPT BOLUS) trial, NCT04102371. We tested whether fluid volume is associated with persistent elevation of urine neutrophil gelatinase-associated lipocalin (Ur-NGAL).

designProspective, non-prespecified cohort study within the PRoMPT BOLUS trial.

settingThree children's hospitals in the United States. PATIENTS: Four hundred seventy-eight patients aged 2 months to younger than 18 years old with septic shock.

interventionsNone. MEASUREMENTS AND MAIN

resultsUr-NGAL, kidney injury molecule-1, liver fatty acid binding protein, and interleukin-18 and plasma cystatin C were collected at presentation (T1), days 2-3 (T2), and before discharge/death (T3). At presentation, 418 (88%) had no or only stage 1 AKI and 60 (12%) had stage 2/3 AKI defined using Kidney Disease Improving Global Outcomes creatinine thresholds. All biomarkers were higher with stage 2/3 compared with no/stage 1 AKI at T1 and T2, but only cystatin C remained higher at T3. Among patients with no/stage 1 AKI at presentation, those with Ur-NGAL greater than or equal to 150 vs. less than 150 ng/mL had fewer hospital-free days (21 [interquartile range (IQR) 15-24] vs. 23 d [IQR 19-25], p = 0.05). After applying inverse probability treatment weighting to balance covariates, 14% of patients who received greater than 100 mL/kg within 48 hours had persistently elevated Ur-NGAL over time compared with 6% who received 40-100 mL/kg (odds ratio 2.7 [95% CI, 1.1-6.2]). Hospital-free days were no different across fluid volume groups.

conclusionsAlthough kidney injury biomarkers mirrored serum creatinine in children with septic shock, elevated Ur-NGAL identified a subset with subclinical AKI with fewer hospital-free days despite no/stage 1 AKI by creatinine. Children receiving greater than 100 mL/kg fluid had greater odds of early and persistently elevated Ur-NGAL, suggesting high fluid volumes may perpetuate initial kidney damage.

Indexed as

Acute Kidney InjuryFluid TherapySaline SolutionShock, SepticAdolescentBiomarkersChildChild, PreschoolCystatin CFatty Acid-Binding ProteinsFemaleHumansInfantInterleukin-18Lipocalin-2MaleBiomarkersCystatin CFABP1 protein, humanFatty Acid-Binding ProteinsInterleukin-18LCN2 protein, humanLipocalin-2Saline Solutionacute kidney injurybiomarkerschildresuscitationsepsis

Identifiers

PMID40172287
PMCPMC12140908

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.