Low hemoglobin levels are independently associated with neonatal acute kidney injury: a report from the AWAKEN Study Group

Pediatric Research (2020)Cite this article

Abstract

Background

Studies in adults showed a relationship between low hemoglobin (Hb) and acute kidney injury (AKI). We performed this study to evaluate this association in newborns.

Methods

We evaluated 1891 newborns from the Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN) database. We evaluated the associations for the entire cohort and 3 gestational age (GA) groups: <29, 29–<36, and ≥36 weeks’ GA.

Results

Minimum Hb in the first postnatal week was significantly lower in neonates with AKI after the first postnatal week (late AKI). After controlling for multiple potential confounders, compared to neonates with a minimum Hb ≥17.0 g/dL, both those with minimum Hb ≤12.6 and 12.7–14.8 g/dL had an adjusted increased odds of late AKI (aOR 3.16, 95% CI 1.44–6.96, p = 0.04) and (aOR 2.03, 95% CI 1.05–3.93; p = 0.04), respectively. This association was no longer evident after controlling for fluid balance. The ability of minimum Hb to predict late AKI was moderate (c-statistic 0.68, 95% CI 0.64–0.72) with a sensitivity of 65.9%, a specificity of 69.7%, and a PPV of 20.8%.

Conclusions

Lower Hb in the first postnatal week was associated with late AKI, though the association no longer remained after fluid balance was included.

Impact

  • The current study suggests a possible novel association between low serum hemoglobin (Hb) and neonatal acute kidney injury (AKI).

  • The study shows that low serum Hb levels in the first postnatal week are associated with increased risk of AKI after the first postnatal week.

  • This study is the first to show this relationship in neonates.

  • Because this study is retrospective, our observations cannot be considered proof of a causative role but do raise important questions and deserve further investigation. Whether the correction of low Hb levels might confer short- and/or long-term renal benefits in neonates was beyond the scope of this study.

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Fig. 1: A flow Diagram of the enrolled patients.
Fig. 2: Box plot of hemoglobin levels by AKI status and day of life.

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Acknowledgements

The authors thank the outstanding work of the following clinical research personnel and colleagues for their involvement in AWAKEN: Ariana Aimani, Samantha Kronish, Ana Palijan, MD, and Michael Pizzi from Montreal Children’s Hospital, McGill University Health Centre, Montreal, QC, Canada; Laila Ajour, BS, and Julia Wrona, BS, from University of Colorado, Children’s Hospital Colorado, Aurora, CO; Melissa Bowman, RN, University of Rochester, Rochester, NY; Teresa Cano, RN, Marta G. Galarza, MD, Wendy Glaberson, MD, Aura Arenas Morales, MD, and Denisse Cristina Pareja Valarezo, MD, from Holtz Children’s Hospital, University of Miami, Miami, FL; Sarah Cashman, BS, and Madeleine Stead, BS, from University of Iowa Children’s Hospital, Iowa City, IO; Jonathan Davis, MD, and Julie Nicoletta, MD, from Floating Hospital for Children at Tufts Medical Center, Tufts University School of Medicine, Boston, MA; Alanna DeMello, British Columbia Children’s Hospital, Vancouver, BC, Canada; Lynn Dill, RN, University of Alabama at Birmingham, Birmingham, AL; Ellen Guthrie, RN, Metro Health Medical Center, Case Western Reserve University, Cleveland, OH; Nicholas L. Harris, BS, and Susan M. Hieber, MSQM, from C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, MI; Katherine Huang and Rosa Waters from University of Virginia Children’s Hospital, Charlottesville, VA; Judd Jacobs, Ryan Knox, BS, Hilary Pitner, MS, and Tara Terrell from Cincinnati Children’s Hospital Medical Center, Cincinnati, OO; Nilima Jawale, MD, Maimonides Medical Center, Brooklyn, NY; Emily Kane, Australian National University, Canberra, ACT, Australia; Vijay Kher, DM, and Puneet Sodhi, MBBS, from Medanta Kidney Institute, The Medicity Hospital, Gurgaon, Haryana, India; Grace Mele, New York College of Osteopathic Medicine, Westbury, NY; Patricia Mele, DNP, Stony Brook Children’s Hospital, Stony Brook, NY; Charity Njoku, Tennille Paulsen, and Sadia Zubair from Texas Children’s Hospital, Baylor College of Medicine, Houston, TX; Emily Pao, University of Washington, Seattle Children’s Hospital, Seattle, WA; Becky Selman, RN, and Michele Spear, CCRC, from University of New Mexico Health Sciences Center Albuquerque, NM; Melissa Vega, PA-C, The Children’s Hospital at Montefiore, Bronx, NY; and Leslie Walther, RN, Washington University, St. Louis, MO. Cincinnati Children’s Hospital Center for Acute Care Nephrology provided funding to create and maintain the AWAKEN Medidata Rave electronic database. The Pediatric and Infant Center for Acute Nephrology (PICAN) provided support for web meetings, the NKC steering committee annual meeting at the University of Alabama at Birmingham (UAB), and support for some of the AWAKEN investigators at UAB (L.B.J., R.J.G.). PICAN is part of the Department of Pediatrics at 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 UL1TR003096). The AWAKEN study at the University of New Mexico was supported by the Clinical and Translational Science Center (CTSC, NIH grant UL1TR001449) and by the University of Iowa Institute for Clinical and Translational Science (U54TR001356). C.L.A. was supported by the Micah Batchelor Foundation. A.A.A. and C.J.R. were supported by the Section of Pediatric Nephrology, Department of Pediatrics, Texas Children’s Hospital. J.R.C. and J.R.S. were supported by a grant from 100 Women Who Care. F.S.C. and K.T.D. were supported by the Edward Mallinckrodt Department of Pediatrics at Washington University School of Medicine. J.F. and A.K. were supported by the Canberra Hospital Private Practice Fund. R.G. and E.R. were supported by the Department of Pediatrics, Golisano Children’s Hospital, University of Rochester. P.E.R. was supported by R01 HL-102497 and R01 DK 49419. S.S. and D.T.S. were supported by the Department of Pediatrics & Communicable Disease, C.S. Mott Children’s Hospital, University of Michigan. S.S. and R.W. were supported by Stony Brook Children’s Hospital Department of Pediatrics funding. Funding sources for this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Author information

Affiliations

  1. Division of Nephrology, Department of Pediatrics, Le Bonheur Children’s Hospital, The University of Tennessee Health Science Center, Memphis, TN, USA

    Arwa Nada & Arwa Nada

  2. Division of Pediatric Nephrology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA

    David Askenazi, Louis J. Boohaker, Linzi Li, David Askenazi, Louis J. Boohaker & Linzi Li

  3. Division of Nephrology, Department of Pediatrics, Nationwide Children’s Hospital, The Ohio State University, Columbus, OH, USA

    John D. Mahan & John D. Mahan

  4. Division of Nephrology, Department of Pediatrics, University of Virginia Health System, Charlottesville, VA, USA

    Jennifer Charlton & Jennifer Charlton

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

    Russell L. Griffin & Russell L. Griffin

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

    David T. Selewski

  7. Children’s of Alabama, University of Alabama at Birmingham, Birmingham, AL, USA

    Namasivayam Ambalavanan

  8. C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, MI, USA

    Subrata Sarkar

  9. Centenary Hospital for Women and Children, Canberra Hospital, Australian National University Medical School, Canberra, ACT, Australia

    Alison Kent & Jeffery Fletcher

  10. Holtz Children’s Hospital, University of Miami, Miami, FL, USA

    Carolyn L. Abitbol, Marissa DeFreitas & Shahnaz Duara

  11. University of Virginia Children’s Hospital, Charlottesville, VA, USA

    Jonathan R. Swanson

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

    Carl D’Angio, Ayesa Mian, Erin Rademacher & Ronnie Guillet

  13. MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA

    Maroun J. Mhanna, Rupesh Raina & Deepak Kumar

  14. University of Iowa Children’s Hospital, Iowa City, IA, USA

    Jennifer G. Jetton, Patrick D. Brophy, Tarah T. Colaizy & Jonathan M. Klein

  15. Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA

    Ayse Akcan-Arikan, Catherine Joseph & Christopher J. Rhee

  16. Maimonides Medical Center, Brooklyn, NY, USA

    Juan C. Kupferman, Alok Bhutada & Shantanu Rastogi

  17. Washington University, St. Louis, MO, USA

    F. Sessions Cole & T. Keefe Davis

  18. Tufts University School of Medicine, Boston, MA, USA

    Lawrence Milner & Alexandra Smith

  19. The Children’s Hospital at Montefiore, Bronx, NY, USA

    Mamta Fuloria, Frederick J. Kaskel & Kimberly Reidy

  20. University of Colorado, Children’s Hospital Colorado, Aurora, CO, USA

    Katja M. Gist, Danielle E. Soranno & Jason Gien

  21. University of Kentucky, Lexington, KY, USA

    Mina Hanna & Aftab S. Chishti

  22. University of Washington, Seattle Children’s Hospital, Seattle, WA, USA

    Sangeeta Hingorani & Michelle Starr

  23. University of New Mexico Health Sciences Center, Albuquerque, NM, USA

    Craig S. Wong, Tara DuPont & Robin Ohls

  24. Apollo Cradle, Gurgaon, Haryana, India

    Surender Khokhar

  25. Children’s National Medical Center, George Washington University School of Medicine and the Health Sciences, Washington, DC, USA

    Sofia Perazzo, Patricio E. Ray & Mary Revenis

  26. Medanta, The Medicity, Gurgaon, India

    Sidharth K. Sethi & Smriri Rohatgi

  27. British Columbia Children’s Hospital, Vancouver, BC, Canada

    Cherry Mammen & Anne Synnes

  28. Cloudnine Hospital, Gurgaon, Haryana, India

    Sanjay Wazir

  29. Toronto Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Michael Zappitelli

  30. Stony Brook School of Medicine, Stony Brook, NY, USA

    Robert Woroniecki & Shanty Sridhar

  31. Cincinnati Children’s Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA

    Stuart L. Goldstein & Amy T. Nathan

  32. Department of Pediatrics, University of New Mexico, Albuquerque, NM, USA

    Amy Staples

  33. McGill University, Montreal, QC, Canada

    Pia Wintermark

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  1. Arwa Nada
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  2. David Askenazi
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  4. Linzi Li
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  5. John D. Mahan
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  7. Russell L. Griffin
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AWAKEN Study Group

Contributions

All listed authors provided substantial contributions to conception and design, acquisition of data, analysis and interpretation of data, drafting the article or revising it critically, and final approval of the version to be published.

Corresponding author

Correspondence to Arwa Nada.

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Competing interests

All authors declare no real or perceived conflicts of interest that could affect the study design, collection, analysis and interpretation of data, writing of the report, or the decision to submit for publication. 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: D.J.A. is a consultant for CHF solutions, Baxter, and Medtronic, and he receives grant funding for studies not related to this manuscript from National Institutes of Health—National Institute of Diabetes and Digestive and Kidney Diseases (NIH-NIDDK, R01 DK103608 and NIH-FDA (R01 FD005092), CHF solutions, and Baxter.

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Nada, A., Askenazi, D., Boohaker, L.J. et al. Low hemoglobin levels are independently associated with neonatal acute kidney injury: a report from the AWAKEN Study Group. Pediatr Res (2020). https://doi.org/10.1038/s41390-020-0963-x

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