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Persistent acute kidney injury and fluid accumulation with outcomes after the Norwood procedure: report from NEPHRON

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Abstract

Background

Cardiac surgery-associated acute kidney injury (CS-AKI) is common, but its impact on clinical outcomes is variable. Parsing AKI into sub-phenotype(s) and integrating pathologic positive cumulative fluid balance (CFB) may better inform prognosis. We sought to determine whether durational sub-phenotyping of CS-AKI with CFB strengthens association with outcomes among neonates undergoing the Norwood procedure.

Methods

Multicenter, retrospective cohort study from the Neonatal and Pediatric Heart and Renal Outcomes Network. Transient CS-AKI: present only on post-operative day (POD) 1 and/or 2; persistent CS-AKI: continued after POD 2. CFB was evaluated per day and peak CFB during the first 7 postoperative days. Primary and secondary outcomes were mortality, respiratory support-free and hospital-free days (at 28, 60 days, respectively). The primary predictor was persistent CS-AKI, defined by modified neonatal Kidney Disease: Improving Global Outcomes criteria.

Results

CS-AKI occurred in 59% (205/347) neonates: 36.6% (127/347) transient and 22.5% (78/347) persistent; CFB > 10% occurred in 18.7% (65/347). Patients with either persistent CS-AKI or peak CFB > 10% had higher mortality. Combined persistent CS-AKI with peak CFB > 10% (n = 21) associated with increased mortality (aOR: 7.8, 95% CI: 1.4, 45.5; p = 0.02), decreased respiratory support-free (predicted mean 12 vs. 19; p < 0.001) and hospital-free days (17 vs. 29; p = 0.048) compared to those with neither.

Conclusions

The combination of persistent CS-AKI and peak CFB > 10% after the Norwood procedure is associated with mortality and hospital resource utilization. Prospective studies targeting intra- and postoperative CS-AKI risk factors and reducing CFB have the potential to improve outcomes.

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Data availability

Requests for proposal concept papers and analyses can be made through the pediatric cardiac critical care consortium (PC4) at https://pc4quality.org/.

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Neonatal and Pediatric Heart and Renal Outcomes Network author list

The following individuals served as collaborators and investigators for the NEPHRON studies. They collaborated in protocol development and review and data analysis, and participated in drafting or review of the manuscript, and their names should be citable by PubMed.

Andrew Smith1, Katie L Brandewie2, Priya N Bhat3, John W Diddle4, Muhammed Ghbeis5, Kenneth E Mah6, Tara M Neumayr7, Tia T Raymond8, Parthak Prodhan9, Xiomara Garcia9, Shannon Ramer9, Mindy Albertson9, David S. Cooper2, Zahidee Rodriguez10, Mary Lukacs2, Michael Gaies2, Amanda Sammons2, Joan Sanchez de Toledo11, Yuliya A Domnina4, Lucas Saenz11, Tracy Baust11, Jane Kluck12, Joshua D Koch13, Jun Sasaki5, Aanish Raees2, Natasha S Afonso3, Erika R O’Neill3, Javier J Lasa3, Patrick A Phillips14, Kristal M Hock14, Santiago Borasino14, David Kwiatkowski6, Joshua Blinder6, Kevin Valentine15, Sachin Tadphale16, Jason R Buckley17, Shanelle Clarke10, Wenying Zhang18, Mohammed Absi16, David J Askenazi.14

1Johns Hopkins University, St. Petersburg, FL, USA.

2Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA.

3Texas Children’s Hospital, Houston, TX, USA.

4Children’s National Medical Center, Washington DC, USA.

5Boston Children’s Hospital, Boston, MA, USA.

6Stanford Children’s Hospital, Palo Alto, CA, USA.

7Washington University School of Medicine, St. Louis, MO, USA

8Medical City Children’s Hospital, Dallas, TX, USA.

9Arkansas Children’s Hospital, Little Rock, AK, USA.

10Children’s Healthcare of Atlanta, Atlanta, GA, USA.

11Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA.

12Children’s Hospital Wisconsin, Milwaukee, WI, USA.

13Phoenix Children’s Hospital, Phoenix, AZ, USA.

14Children’s of Alabama, Birmingham, AB, USA.

15Riley Hospital for Children, Indianapolis, IN, USA.

16LeBonheur Children’s Hospital, Memphis, TN, USA.

17Medical University of South Carolina, Charleston, SC, USA.

18University of Michigan, Ann Arbor, MI, USA.

Funding

This study was supported by the Heart Institute Research Core (HIRC) at Cincinnati Children’s Hospital with additional funding from Castin’ ‘N Catchin’ Charity Organization. The funding sources for this study had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave., MLC 2003, CincinnatiCincinnati, OH, 45226, USA

    Denise C. Hasson, Jeffrey A. Alten, David S. Winlaw, Stuart L. Goldstein & Katja M. Gist

  2. Hassenfeld Children’s Hospital, Division of Pediatric Critical Care, NYU Langone, New York, NY, USA

    Denise C. Hasson

  3. Department of Pediatrics, Medical College of Wisconsin, Children’s Wisconsin, Milwaukee, WI, USA

    Rebecca A. Bertrandt

  4. Department of Biostatistics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Huaiyu Zang

  5. Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA

    David T. Selewski

  6. Department of Pediatrics, Primary Children’s Hospital, University of Michigan Medical School, Ann Arbor, MI, USA

    Garrett Reichle

  7. University of Utah, Salt Lake City, UT, USA

    David K. Bailly

  8. Department of Pediatrics, Nationwide Children’s Hospital, Columbus, OH, USA

    Catherine D. Krawczeski

  9. Lurie Children’s Hospital, Department of Pediatric Surgery, Northwestern University School of Medicine, Chicago, IL, USA

    David S. Winlaw

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  1. Denise C. Hasson
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  2. Jeffrey A. Alten
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  4. Huaiyu Zang
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  5. David T. Selewski
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  6. Garrett Reichle
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  7. David K. Bailly
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  10. Stuart L. Goldstein
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Consortia

on behalf of the Neonatal, Pediatric Heart, Renal Outcomes Network (NEPHRON) Investigators

  • Andrew Smith
  • , Katie L. Brandewie
  • , Priya N. Bhat
  • , John W. Diddle
  • , Muhammed Ghbeis
  • , Kenneth E. Mah
  • , Tara M. Neumayr
  • , Tia T. Raymond
  • , Parthak Prodhan
  • , Xiomara Garcia
  • , Shannon Ramer
  • , Mindy Albertson
  • , David S. Cooper
  • , Zahidee Rodriguez
  • , Mary Lukacs
  • , Michael Gaies
  • , Amanda Sammons
  • , Joan Sanchez de Toledo
  • , Yuliya A. Domnina
  • , Lucas Saenz
  • , Tracy Baust
  • , Jane Kluck
  • , Joshua D. Koch
  • , Jun Sasaki
  • , Aanish Raees
  • , Natasha S. Afonso
  • , Erika R. O’Neill
  • , Javier J. Lasa
  • , Patrick A. Phillips
  • , Kristal M. Hock
  • , Santiago Borasino
  • , David Kwiatkowski
  • , Joshua Blinder
  • , Kevin Valentine
  • , Sachin Tadphale
  • , Jason R. Buckley
  • , Shanelle Clarke
  • , Wenying Zhang
  • , Mohammed Absi
  •  & David J. Askenazi

Contributions

DH and KMG conceptualized and designed the study, assisted with data analysis and interpretation, drafted the initial manuscript, and reviewed and revised the manuscript. HZ performed statistical analysis and reviewed and revised the manuscript. JA conceptualized and designed the study, provided support and mentorship, and reviewed and revised the manuscript. All other authors assisted with the design of the study, data interpretation, and reviewed and revised the manuscript for important intellectual content. All authors approve the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Katja M. Gist.

Ethics declarations

All authors report no real or perceived conflicts of interest that could affect the study design, collection, analysis, and interpretation of data, the writing of the report, or the decision to submit the manuscript for publication. For full disclosure, we provide the additional list of authors’ other funding not directly related to this study. DA is a consultant for Baxter, Nuwellis, Medtronic Bioporto, and Seastar. His institution receives grant funding for education and research that is not related to this project from NIH, Baxter, Nuwellis, Medtronic, Bioporto, and Seastar. He has patents pending on inventions to improve the kidney care of neonates. He is the Founder and Chief Scientific Officer for Zorro-Flow. KMG receives consultant fees from Bioporto Diagnostics and Potrero Medical. SLG is a consultant for Baxter, Medtronic, Bioporto, and Protrero. He is the founder and Chief Scientific Officer for Medibeacon. No other disclosures were reported.

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Hasson, D.C., Alten, J.A., Bertrandt, R.A. et al. Persistent acute kidney injury and fluid accumulation with outcomes after the Norwood procedure: report from NEPHRON. Pediatr Nephrol 39, 1627–1637 (2024). https://doi.org/10.1007/s00467-023-06235-y

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