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

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.

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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.

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Correspondence to Arwa Nada.

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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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