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Prevalence of acute kidney injury (AKI) in extremely low gestational age neonates (ELGAN)

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Abstract

Background

To determine the prevalence and severity of acute kidney injury (AKI) at different time frames in relation to gestational age (GA) and birthweight (BW) in extremely low gestational age neonates (ELGAN). Our hypothesis is that ELGAN with lower GA and lower BW have higher AKI rates.

Methods

A total of 923 ELGAN enrolled in the Preterm Erythropoietin Neuroprotection Trial were evaluated from birth until death or hospital discharge. AKI was defined according to kidney disease: improving global outcomes (KDIGO) definition from clinically-derived serum creatinine (SCr) measurements. Severe AKI was defined as stage 2 or higher.

Results

For the entire cohort, 351/923 (38.0%, CI = 34.8–41.3%) had at least one episode of stage 1 or higher AKI and 168/923 (18.2%, CI = 15.7–20.7%) had at least one episode of severe (stage 2 or higher) AKI. The prevalence of AKI stage 1 or higher for the entire cohort during the early (days 3–7), middle (days 8–14), and late follow-up period (after day 14) was 112/923 (12.1%, CI = 10.0–14.3%), 142/891 (15.9%, CI = 13.5–18.4%), and 249/875 (28.5%, CI = 25.4–31.5%), respectively. The rates of severe AKI during the hospital course were 27.8%, 21.9%, 13.6%, and 9.4% for the 24-, 25-, 26-, and 27-week GA groups, respectively. AKI rates were significantly higher with decreasing GA and decreasing BW for stated time trends (all p < 0.01 using tests for trend).

Conclusions

AKI is relatively common in ELGAN during their initial hospital course and is associated with lower GA and BW.

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Abbreviations

AKI:

Acute kidney injury

NICU:

Neonatal intensive care unit

SCr:

Serum creatinine

PENUT:

Preterm Epo Neuroprotection Trial

ELGAN:

Extreme low gestational age neonates

REPaIReD:

Recombinant Erythropoietin for Protection of Infant Renal Disease

GA:

Gestational age

Epo:

Erythropoietin

GEE:

General estimating equations

AWAKEN:

Awareness of Worldwide Acute Kidney Epidemiology in Neonates

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Acknowledgments

We would like to thank Lynn Dill, RN, and Emily Pao for their assistance in coordinating the REPaIReD study. We would like to thank the investigators, clinicians, research personnel, study teams and families who participated in the PENUT Trial.

Funding sources

Recombinant Erythropoietin for Protection of Infant Renal Disease (REPaIReD) Study is an NIH NIDDK funded (R01 DK103608) ancillary study designed to look at kidney outcome in patients enrolled in the Preterm Erythropoietin Neuroprotection Trial (PENUT Trial) which is an NIH NINDS funded (U01 NS077953, U01 NS077955) trial. The clinicaltrials.gov identifier is NCT01378273.

Prior Presentations

Some data presented in this study was previously presented as oral presentations to the 23rd AKI/CRRT meeting (March 2018) and the Pediatric Academic Society meeting (May 2018).

PENUT Primary Investigators

Sandra E. Juul1, Bryan A. Comstock1, Rajan Wadhawan2; Dennis E. Mayock1, Sherry E. Courtney3; Tonya Robinson4; Kaashif A. Ahmad5; Ellen Bendel-Stenzel6; Mariana Baserga7; Edmund F. LaGamma8; L. Corbin Downey9; Raghavendra Rao10; Nancy Fahim10; Andrea Lampland11; Ivan D. Frantz, III12; Janine Y. Khan13; Michael Weiss14; Maureen M. Gilmore15; Robin Ohls16; Nishant Srinivasan17; Jorge E. Perez18; Victor McKay19; Phuong T. Vu1; Patrick J. Heagerty1; and the PENUT Trial Consortium

PENUT Co-Investigators

Billy Thomas3, Nahed Elhassan3, Sarah Mulkey3, Philip Dydynski4, Vivek K. Vijayamadhavan5, Neil Mulrooney6, Bradley Yoder7, Jordan S. Kase8, Jennifer Check9, Semsa Gogcu9, Erin Osterholm10, Sara Ramel10, Catherine Bendel10, Cheryl Gale10, Thomas George10, Michael Georgieff10, Tate Gisslen10, Sixto Guiang III10, Anne Hall10, Dana Johnson10, Katie Pfister10, Heather Podgorski10, Kari Roberts10, Erin Stepka10, Melissa Engel10, Heidi Kamrath10, Johannah Scheurer10, Angela Hanson10, Katherine Satrom10, Susan Pfister10, Ann Simones10, Erin Plummer10, Elizabeth Zorn10, Camilia R. Martin12, Deirdre O’Reilly12, Nicolas Porta13, Catalina Bazacliu14, Jonathan Williams14, Dhanashree Rajderkar14, Frances Northington15, Raul Chavez Valdez15, Sandra Beauman16, Patel Saurabhkumar17, Magaly Diaz-Barbosa18, Arturo Serize18, Jorge Jordan18

PENUT Research Coordinators

Debbie Ott1, Ariana Franco Mora1, Pamela Hedrick1, Vicki Flynn1, Amy Silvia2, Bailey Clopp2, John B. Feltner2, Isabella Esposito2, Stephanie Hauge2, Samantha Nikirk2, Andrea Purnell3, Emilie Loy3, Natalie Sikes3, Melanie Mason3, Jana McConnell3, Tiffany Brown3, Henry Harrison3, Denise Pearson3, Tammy Drake3, Jocelyn Wright3, Debra Walden3, Annette Guy3, Jennifer Nason4, Morgan Talbot4, Kristen Lee4, Sarah Penny4, Terri Boles4, Melanie Drummond5, Katy Kohlleppel5, Charmaine Kathen5, Brian Kaletka6, 11, Shania Gonzales6, 11, Cathy Worwa6, 11, Molly Fisher, 11, Tyler Richter6, 11, Alexander Ginder6, 11, Brixen Reich7, Carrie Rau7, Manndi Loertscher7, Laura Bledsoe7, Kandace McGrath7, Kimberlee Weaver Lewis7, Jill Burnett7, Susan Schaefer7, Karie Bird7, Clare Giblin8, Rita Daly8, Kristi Lanier9, Kelly Warden9, Jenna Wassenaar10, Jensina Ericksen10, Bridget Davern10, Mary Pat Osborne10, Brittany Gregorich10, Neha Talele12, Evelyn Obregon12, Tiglath Ziyeh12, Molly Clarke12, Rachel E Wegner12, Palak Patel12, Molly Schau13, Annamarie Russow13, Kelly Curry14, Susan Sinnamon14, Lisa Barnhart14, Charlamaine Parkinson15, Sandra Beauman16, Mary Hanson16, Elizabeth Kuan16, Conra Backstrom Lacy16, Edshelee M. Galvis18, Susana Bombino18, Denise Martinez19, Suzi Bell19, Corrie Long19

PENUT Follow-Up Personnel

Cathy Longa2, Michael Westerveld2, Stacy McConkey2, Anne Hay1, Niranjana Natarajan1, Shari Gaudette3, Sarah Cobb3, Gregory Sharp3, Elizabeth Schumacher4, Leslie Schuschke4, Charlotte Frey5, Mario Fierro5, Lois Gilmore6, Pamela Lundequam6, Ronald Hoekstra6, Anastasia Ketko6, Nina Perdue6, Sean Cunningham7, Kelly Stout7, Becky Hall7, Galina Morshedzadeh7, Betsy Ostrander7, Sarah Winter7, Lauren Cox8, Jordan S. Kase8, Matthew A. Rainaldi8, Sarah Hensley9; Melissa Morris9, Dia Roberts9, Semsa Gogcu9, Melissa Tuttle9; Christopher Boys10, Solveig Hultgren10, Elizabeth I. Pierpont10, Nancy Fahim10, Tom George10, Erin Osterholm10, Michael Georgieff10, Kelly E. King10, Katherine Bataglia11, Cathy Neis11, Mark Bergeron11, Cristina Miller11, Cara Accomando12, Jennifer Anne Gavin12, Elizabeth Maczek12, Susan Marakovitz12, Aimee Knorr12, Vincent C. Smith12, Jane E. Stewart12, Marie Weissbourd13, Raye-Ann deRegnier13, Nana Matoba13, Shelly C. Heaton12, Erika M. Cascio12, Janet Brady14, Suman Ghosh14, Jessica Ditto15, Mary Leppert15, Jean Lowe16, Janell Fuller16, Tara DuPont16, Robin Ohls16, Pamela Kloska17, Saurabh Patel17, Lauren Carbonell18, Anna Maria Patino-Fernandez18 Carmen de Lerma18, Susana Bombino18, Arturo Serize18, Kelly McDonough18, Maiana De Cortada18, Lacy Chavis19, Jane Shannon19

University of Washington Data Coordinating Center

Bryan A. Comstock1, Patrick J. Heagerty1, Mark A. Konodi1, Christopher Nefcy1, Phuong T. Vu1

PENUT Follow-Up Committee

Karl C. K. Kuban20, Jean R. Lowe16, T. Michael O’Shea21

Radiology Committee

Manjiri Dighe1, Todd Richards1, Dennis W. W. Shaw1, Colin Studholme1, Christopher M. Traudt1

PENUT Executive Committee

Roberta Ballard22, Bryan A. Comstock1, Adam Hartman23, Scott Janis23, Sandra E. Juul1, Dennis E. Mayock1, T. Robin Ohls16, Michael O’Shea21

DSMB

Ronnie Guillet 24, M. Bethany Ball25, Hannah Glass22, Ben Saville26, Michael Schreiber27

  1. 1.

    University of Washington (Seattle, Washington)

  2. 2.

    AdventHealth for Children, (Orlando, Florida)

  3. 3.

    University of Arkansas for Medical Sciences (Little Rock, Arkansas)

  4. 4.

    University of Louisville, (Louisville, Kentucky)

  5. 5.

    Methodist Children’s Hospital (San Antonio, Texas)

  6. 6.

    Children’s Hospital and Clinics of Minnesota (Minneapolis, Minnesota)

  7. 7.

    University of Utah (Salt Lake City, Utah)

  8. 8.

    Maria Fareri Children’s Hospital at Westchester Medical Center (Valhalla, New York)

  9. 9.

    Wake Forest School of Medicine (Winston-Salem, North Carolina)

  10. 10.

    University of Minnesota Masonic Children’s Hospital (Minneapolis, Minnesota)

  11. 11.

    Children’s Minnesota (St. Paul, Minnesota)

  12. 12.

    Beth Israel Deaconess Medical Center (Boston, Massachusetts)

  13. 13.

    Prentice Women’s Hospital (Chicago, Illinois)

  14. 14.

    University of Florida (Gainesville, Florida)

  15. 15.

    Johns Hopkins University (Baltimore, Maryland)

  16. 16.

    University of New Mexico (Albuquerque, New Mexico)

  17. 17.

    Children’s Hospital of the University of Illinois (Chicago, Illinois)

  18. 18.

    South Miami Hospital (South Miami, Florida)

  19. 19.

    Johns Hopkins All Children’s Hospital (St. Petersburg, Florida)

  20. 20.

    Boston University Medical Center (Boston, Massachusetts)

  21. 21.

    University of North Carolina School of Medicine (Chapel Hill, North Carolina)

  22. 22.

    University of California San Francisco School of Medicine (San Francisco, California)

  23. 23.

    National Institute of Neurological Disorders and Stroke

  24. 24.

    University of Rochester Medical Center (Rochester, New York)

  25. 25.

    Stanford University and Lucile Packard Children’s Hospital (Palo Alto, California)

  26. 26.

    Vanderbilt University Medical Center (Nashville, Tennessee)

  27. 27.

    University of Chicago (Chicago, Illinois)

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA

    David J. Askenazi

  2. Birmingham, USA

    David J. Askenazi

  3. Department of Biostatistics, University of Washington, Seattle, WA, USA

    Patrick J. Heagerty & Robert H. Schmicker

  4. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

    Russell Griffin

  5. University of Rochester/Golisano Children’s Hospital, Rochester, NY, USA

    Patrick Brophy

  6. Department of Pediatrics, University of Washington/Seattle Children’s Hospital, Seattle, WA, USA

    Sandra E. Juul, Dennis E. Mayock & Sangeeta Hingorani

  7. Department of Pediatrics, Cincinnati Children’s Hospital Medical Center/University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA

    Stuart L. Goldstein

Authors
  1. David J. Askenazi
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  2. Patrick J. Heagerty
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  4. Russell Griffin
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  9. Sangeeta Hingorani
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Consortia

on behalf of the PENUT Trial Consortium

Contributions

Conceptualization/design: David J. Askenazi, Patrick J. Heagerty, Russell Griffin, Patrick Brophy, Sandra E. Juul, Stuart L. Goldstein, Sangeeta Hingorani; Methodology: David J. Askenazi, Patrick Brophy, Stuart L. Goldstein MD, Sangeeta Hingorani; Investigation: David Askenazi, Sandra E. Juul, Dennis E. Mayock, Stuart L. Goldstein, Sangeeta Hingorani; Funding: Sandra E. Juul, Stuart L. Goldstein, Sangeeta Hingorani; Data curation: David J. Askenazi, Dennis E. Mayock, Stuart L. Goldstein; Formal analysis: David J. Askenazi, Patrick J. Heagerty, Robert H. Schmicker, Stuart L. Goldstein, Sangeeta Hingorani; Writing—original draft preparation: David J. Askenazi; Writing—review and editing: David J. Askenazi, Patrick J. Heagerty, Robert H. Schmicker, Russell Griffin, Patrick Brophy, Sandra E. Juul, Dennis E. Mayock, Stuart L. Goldstein, Sangeeta Hingorani.

Corresponding author

Correspondence to David J. Askenazi.

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Disclaimer

Funding sources for this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Conflict of interest

For full disclosure, we provide here an additional list of other author’s commitments and funding sources that are not directly related to this study:

David J Askenazi serves on the speaker board for Baxter (Baxter, USA), and the Acute Kidney Injury (AKI) Foundation (Cincinnati, OH, USA). He is consultant for Baxter, CHF solutions, and Medtronic. He also receives grant funding for studies not related to this project from Baxter, CHF solutions, and National Institutes of Health (R01 FD005092, U34 KD117128) and the Pediatric and Infant Center for Acute Nephrology (PICAN). PICAN is part of the Department of Pediatrics at the University of Alabama at Birmingham (UAB), and is funded by Children’s of Alabama Hospital, the Department of Pediatrics, UAB School of Medicine, and UAB’s Center for Clinical and Translational Sciences (CCTS, NIH grant UL1TR001417).

Dr. Goldstein reports personal fees from and a position as a consultant to CHF Solutions Inc., Renibus, ExThera, Reata and Medtronic Inc. Dr. Goldstein receives grant funding from and serves as a consultant and on a Speaker’s Bureau for Baxter Healthcare, Inc. Dr. Goldstein receives grant funding and serves as a consultant for BioPorto, Inc. Dr. Goldstein serves on a Speaker’s Bureau for Fresenius Medical Corporation.

Mr. Schmicker receives grant funding for studies not related to this project from NHLBI and PCORI.

Ethics committee approval

The University of Washington Institutional Review Board (IRB) approved this collaborative study, and each center received approval from their respective IRBs.

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Askenazi, D.J., Heagerty, P.J., Schmicker, R.H. et al. Prevalence of acute kidney injury (AKI) in extremely low gestational age neonates (ELGAN). Pediatr Nephrol 35, 1737–1748 (2020). https://doi.org/10.1007/s00467-020-04563-x

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