Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates 2.0 (AWAKEN 2)

Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates 2.0: Towards Expanding Our Understanding of Neonatal Acute Kidney Injury

There is a growing focus on short- and long-term kidney health in neonates, including those with acute kidney injury (AKI). AKI occurs commonly in the Neonatal Intensive Care Unit (NICU) and is associated with adverse outcomes. In addition to poor outcomes during the hospitalization, infants discharged from the NICU may have an increased burden of kidney disease during childhood. Studies of long-term kidney function in children born prematurely show a fourfold increase in chronic kidney disease (CKD) by adolescence and into adulthood.

Despite the landmark findings of the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study, the limitations of this study are notable. First, the AWAKEN study enrolled infants admitted in 2014, making the data now over 10 years old. Much has changed in neonatal practice (e.g. increased AKI awareness, treatment strategies). Secondly, the findings of the AWAKEN study were geographically limited. While the AWAKEN study was multi-national and multi-center, it represented only 24 centers (22 from North America, 1 from India and 1 from Australia). Finally, information collected from AWAKEN ended at hospital discharge.

The investigators seek to leverage the strength of the Neonatal Kidney Collaborative along with other organizations and collaboratives interested in neonatal kidney health to address these gaps. Therefore, the investigators are conducting a second, modified iteration of this study entitled "AWAKEN 2.0". AWAKEN 2.0 will be a multi-center multi-national retrospective analysis utilizing similar methodology to the AWAKEN study.

Study Overview

• Status: Enrolling by invitation
• Conditions: Hypertension; Acute Kidney Injury; Fluid Overload; Risk Factors; Epidemiology; Chronic Kidney Disease(CKD); Prematurity Complications

Detailed Description

AWAKEN 2.0 is a multi-center multi-national retrospective analysis utilizing similar methodology to the AWAKEN study. The investigators will capture information on all infants admitted to participating level 3 and 4 NICUs between January 1-March 31, 2019, to answer specific hypothesis regarding the following three inter-connected but independent specific aims:

Specific Aim 1. Describe prevalence of AKI in a multi-national multi-center retrospective cohort, 5 years after the original AWAKEN study.

1. Primary hypothesis: The investigators hypothesize that rates of neonatal AKI are higher than the rate described in the original AWAKEN study.

2. Population:

   1. Inclusion Criteria include all infants admitted to participating NICUs between 1/1/19- 3/31/19 and receiving > 48 hours of IV fluids
   2. Exclusion Criteria include age > 14 days at admission, congenital heart disease requiring transfer for escalation of CHD care and/or surgery within the first 7 days, lethal chromosomal anomalies and/or neonatal mortality <48 hours
3. Primary Outcome - Neonatal AKI
4. Potential confounders - gestational age, birth weight, 5 minute APGAR score, multiple gestation, significant renal anomalies, site characteristics.

Specific Aim 2. Determine if AKI is independently associated with mortality, length of stay, and discharge serum creatinine (SCr).

1. The investigators hypothesize that higher stages of AKI are associated with higher mortality, longer lengths of stay and higher serum creatinine at discharge, even after controlling for confounding factors.
2. Populations - Same as Specific Aim 1.
3. Primary Exposure - Neonatal AKI definitions (table 3)
4. Primary Outcome - Survival
5. Secondary outcomes will include: Hospital length of stay, BPD.
6. Potential confounders - gestational age, birth weight, 5 minute APGAR score, multiple gestation, significant renal anomalies,
7. Exploratory outcomes - recognize that the proposed definition may not be the best definition to predict clinical outcomes. Also recognize that there may be a need to have different definitions for premature infants. The investigators plan to explore how other definitions reported in the literature can predict these outcomes (for example using the 90th % for normative values). In addition, this will have the largest comprehensive database to explore new definitions which could incorporate fluid balance and other factors.

Specific Aim 3. Determine if AKI can predict chronic kidney disease, recurrent AKI and hypertension during early childhood.

1. The investigators hypothesize that higher stages of AKI are associated with chronic kidney disease and recurrent AKI during early childhood.
2. Population - Same as Specific Aim 1
3. Primary Exposure - Neonatal AKI definitions (table 3)
4. Primary Outcome - Childhood CKD
5. Secondary Outcomes - Childhood hypertension, recurrent AKI and childhood ESRD.

Each participating site will screen all neonates admitted to the NICU during the 3 months of study and capture additional data on those who meet the same inclusion and exclusion criteria as the original cohort. There will be 6 different integrated forms.

1. Screening form (all infants)
2. Baseline form for included infants (maternal demographic data, admission indication)
3. First 14 days form (i.e. urine output, medications and respiratory support)
4. Serum creatinine data (all values from date of birth to date of IRB approval)
5. Discharge form (discharge diagnoses, medications, follow-up anticipated)
6. Follow-up Information (clinically obtained follow-up after discharge)

• Study Type: Observational
• Enrollment (Estimated): 4000

Contacts and Locations

Study Locations

• Australia
  • Perth, Australia
    • Perth Children's Hospital
  • Victoria
    • Melbourne, Victoria, Australia
      • The Royal Children's Hospital Melbourne
• Brazil
  • Florianópolis, Brazil
    • Joana de Gusmao Children's Hospital
  • Porto Alegre, Brazil
    • Hospital de Clínicas de Porto Alegre
• Canada
  • Calgary, Canada
    • Alberta Children's Hospital/University of Calgary
  • Edmonton, Canada
    • Stollery Children's Hospital
  • Hamilton, Canada
    • McMaster Children's Hospital
  • Montreal, Canada
    • McGill University
  • Toronto, Canada
    • Mount Sinai Hospital
  • Toronto, Canada
    • Sunnybrook Health Sciences Center
  • Ontario
    • Toronto, Ontario, Canada
      • The Hospital for Sick Children
• Colombia
  • Bogotá, Colombia
    • Hospital Occidente de Kennedy
  • Cali, Colombia
    • Fundacion Valle del Lili Cali
  • Medellín, Colombia
    • Clínica Universitaria Bolivariana
• Czechia
  • Prague, Czechia
    • Institute for the Care of Mother and Child
• Germany
  • Cologne, Germany
    • University of Cologne
• Greece
  • Athens, Greece
    • Aghia Sofia Children's Hospital
  • Heraklion, Greece
    • University Hospital of Heraklion
  • Thessaloniki, Greece
    • Aristotle University
  • Thessaloniki, Greece
    • Hippokration General Hospital of Thessaloniki
• Hungary
  • Szeged, Hungary
    • University of Szeged Children's Hospital
• India
  • Bengaluru, India
    • St. John's Medical College Hospital
  • Chennai, India
    • Dr. Mehta's Hospitals
  • Vellore, India
    • Christian Medical College
• Mexico
  • Veracruz, Mexico
    • Centro de Alta Especialidad del Estado de Veracruz
• Netherlands
  • Nijmegen, Netherlands
    • Amalia Children's Hospital Radboudumc
• Nigeria
  • Ibadan, Nigeria
    • University of Ibadan
• Portugal
  • Lisbon, Portugal
    • Hospital Santa Maria, Unidade Local de Saude de Santa Maria
  • Porto, Portugal
    • Centro Materno Infantil de Norte Albino Aroso, Unidade Local de Saude de Santo Antonio
  • Porto, Portugal
    • ULS Sao Joan
• Slovenia
  • Ljubljana, Slovenia
    • University Medical Centre Ljubljana
• Spain
  • Cadiz, Spain
    • Puerta del Mar University Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye)
    • Çukurova University
  • Ankara, Turkey (Türkiye)
    • Ankara Bilkent City Hospital, Children Hospital
  • Istanbul, Turkey (Türkiye)
    • Marmara University Pendik Research and Training Hospital
• Uganda
  • Kampala, Uganda
    • St Francis Nsambya
• Ukraine
  • Chernivtsi, Ukraine
    • Bukovinian State Medical University
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • University of Arkansas for Medical Sciences
  • California
    • Palo Alto, California, United States, 94304
      • Stanford Children's
    • San Diego, California, United States, 92123
      • Rady Children's Hospital/UCSD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Hospital
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's / Nichlaus Children's Hospital
    • South Miami, Florida, United States, 33176
      • Baptist Health South Florida/South Miami Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Healthcare / Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital of Chicago
    • Springfield, Illinois, United States, 62702
      • SIU
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
    • St Louis, Missouri, United States, 63110
      • Washington University
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Children's Nebraska
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center
    • Queens, New York, United States, 11040
      • Cohen Children's Hospital
    • Rochester, New York, United States, 14642
      • University of Rochester / Golisano Children's Hospital
    • Stony Brook, New York, United States, 11794
      • Stony Brook Medicine
    • The Bronx, New York, United States, 10467
      • Children's Hospital at Montefiore
    • Westchester, New York, United States, 10595
      • Westchester Medical Center/Maria Fareri Children's Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Monroe Carell Jr. Children's Hospital at Vanderbilt
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • Lubbock, Texas, United States, 79415
      • Texas Tech
    • San Antonio, Texas, United States, 78207
      • CHRISTUS Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Golisano Children's Hospital at University of Vermont Health
  • Virginia
    • Charlottesville, Virginia, United States, 22930
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital / University of Washington
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin / Children's Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The investigators will conduct a multi-center retrospective cohort study. All infants admitted to the NICU between January 1, 2019 and March 31, 2019 will be screened for the study.The investigators will enroll eligible infants who meet inclusion and exclusion criteria at each center for 3 consecutive months. Based on average admissions for 2018 at our centers who meet inclusion and exclusion criteria, it is estimated that it can enroll approximately 4000 infants during this time.

Description

Inclusion Criteria:

1. All infants born or admitted to a participating level 3 or 4 NICU between 1/1/19- 3/31/19 will be screened.
2. Infants who received intravenous fluids for > 48 hours will be eligible.

Exclusion Criteria:

1. Age > 14 days at admission
2. Congenital heart disease requiring transfer for escalation of CHD care and/or surgery within the first 7 days
3. Lethal chromosomal anomalies
4. Neonatal mortality <48 hours

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Neonates at Risk of Kidney Disease; Inclusion Criteria; Admitted to participating NICUs between 1/1/19- 3/31/19; > 48 hours of IV fluids Exclusion Criteria; Age > 14 days at admission; Congenital heart disease requiring transfer for escalation of CHD care and/or surgery within the first 7 days; Lethal chromosomal anomalies; Neonatal mortality <48 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal Acute Kidney Injury	The investigators will evaluate the rate of neonatal AKI among infants that meet inclusion criteria across all sites. Neonatal Acute Kidney Injury will be defined by the standard neonatal definitions, including serum creatinine values and urine output (when available). Furthermore, investigators will examine if different thresholds or definitions of AKI will better predict outcomes.	Up to 6 months or NICU discharge, whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk factors for Neonatal AKI	Define the major risk factors associated with neonatal AKI. The investigators will randomly split the cohort into two groups. The investigators will develop a risk factor prediction model with the first group, and test the ability of the model to predict AKI with the second group.	Up to 6 months or NICU discharge, whichever comes first
Fluid Overload	Fluid overload will be calculated based on daily weights and intake and output values. We will determine how fluid balance during the first few weeks of life relates to biochemical data and clinical outcomes.	NICU admission through discharge.
Mortality	Determine if the KDIGO AKI definition adapted to neonates can predict mortality. Investigators will also evaluate if other thresholds or proposed AKI definitions can better predict mortality.	Up to 6 months or NICU discharge, whichever comes first
Chronic Kidney Disease	In infants with available follow-up data clinically obtained, investigators will determine the rates of both clinically diagnosed (by ICD code or note) and laboratory determined Chronic Kidney Disease (using the CKID-U25 eGFR definitions).	NICU discharge to 5 year follow-up
Hypertension	In infants with available follow-up data clinically obtained, investigators will determine the rates of both clinically diagnosed (by ICD code or note) and value determined hypertension (using AAP Hypertension thresholds)	NICU discharge to 5 year follow-up
Proteinuria	In infants with available follow-up data clinically obtained, investigators will determine the rates of both clinically diagnosed (by ICD code or note) and laboratory determined proteinuria.	NICU discharge to 5 year follow-up

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: Neonatal Kidney Collaborative

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 4, 2025
• First Submitted That Met QC Criteria: February 7, 2025
• First Posted (Actual): February 12, 2025

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: hypertension; chronic kidney disease; acute kidney injury; prematurity; neonates
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Premature Birth; Hypertension; Acute Kidney Injury; Renal Insufficiency, Chronic; Edema
• Other Study ID Numbers: 23847

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: As a retrospective study and based on terms of the data sharing agreements between sites, individual patient level data will not be made available. Investigators that have questions that may be answered by the data will be able to present proposal to request secondary data analyses to be conducted on de-identified data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No