Clinical Research Article | Published:

Optimizing the AKI definition during first postnatal week using Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) cohort

Abstract

Background

Neonates with serum creatinine (SCr) rise ≥0.3 mg/dL and/or ≥50% SCr rise are more likely to die, even when controlling for confounders. These thresholds have not been tested in newborns. We hypothesized that different gestational age (GA) groups require different SCr thresholds.

Methods

Neonates in Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) with ≥1 SCr on postnatal days 1–2 and ≥1 SCr on postnatal days 3–8 were assessed. We compared the mortality predictability of SCr absolute (≥0.3 mg/dL) vs percent (≥50%) rise. Next, we determine usefulness of combining absolute with percent rise. Finally, we determined the optimal absolute, percent, and maximum SCr thresholds that provide the highest mortality area under curve (AUC) and specificity for different GA groups.

Results

The ≥0.3 mg/dL rise outperformed ≥50% SCr rise. Addition of percent rise did not improve mortality predictability. The optimal SCr thresholds to predict AUC and specificity were ≥0.3 and ≥0.6 mg/dL for ≤29 weeks GA, and ≥0.1 and ≥0.3 mg/dL for >29 week GA. The maximum SCr value provides great specificity.

Conclusion

Unique SCr rise cutoffs for different GA improves outcome prediction. Percent SCr rise does not add value to the neonatal AKI definition.

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Acknowledgements

The authors would like to thank Krysta Smith (Department of Pediatrics, University of Alabama at Birmingham) for help with technical editing and proofreading of this manuscript. The authors would also like to thank the outstanding work of the following clinical research personnel and colleagues for their involvement in AWAKEN: Ariana Aimani, Samantha Kronish, Ana Palijan, MD, Michael Pizzi—Montreal Children’s Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Laila Ajour, BS, Julia Wrona, BS—University of Colorado, Children’s Hospital Colorado, Aurora, Colorado, USA; Melissa Bowman, RN—University of Rochester, Rochester, New York, USA; Teresa Cano, RN, Marta G. Galarza, MD, Wendy Glaberson, MD, Aura Arenas Morales, MD, Denisse Cristina Pareja Valarezo, MD—Holtz Children’s Hospital, University of Miami, Miami, Florida, USA; Sarah Cashman, BS, Madeleine Stead, BS—University of Iowa Children’s Hospital, Iowa City, Iowa, USA; Jonathan Davis, MD, Julie Nicoletta, MD—Floating Hospital for Children at Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA; Alanna DeMello—British Columbia Children’s Hospital, Vancouver, British Columbia, Canada; Lynn Dill, RN—University of Alabama at Birmingham, Birmingham, Alabama, USA; Ellen Guthrie, RN—MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA, Nicholas L. Harris, BS, Susan M. Hieber, MSQM—C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan, USA; Katherine Huang, Rosa Waters—University of Virginia Children’s Hospital, Charlottesville, Virginia, USA; Judd Jacobs, Ryan Knox, BS, Hilary Pitner, MS, Tara Terrell—Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; Nilima Jawale, MD—Maimonides Medical Center, Brooklyn, New York, USA; Emily Kane—Australian National University, Canberra, Australia; Vijay Kher, DM, Puneet Sodhi, MBBS—Medanta Kidney Institute, The Medicity Hospital, Gurgaon, Haryana, India; Grace Mele—New York College of Osteopathic Medicine, Westbury, New York, USA; Patricia Mele, DNP—Stony Brook Children’s Hospital, Stony Brook, New York, USA; Charity Njoku, Tennille Paulsen, Sadia Zubair—Texas Children’s Hospital, Baylor College of Medicine, Houston, Texas, USA; Emily Pao—University of Washington, Seattle Children’s Hospital, Seattle, Washington, USA; Becky Selman RN, Michele Spear, CCRC—University of New Mexico Health Sciences Center Albuquerque, New Mexico, USA; Melissa Vega, PA-C—The Children’s Hospital at Montefiore, Bronx, New York, USA); and Leslie Walther RN—Washington University, St. Louis, Missouri, USA.

Neonatal Kidney Collaborative Contributors:

The following individuals served as collaborators and site investigators for the AWAKEN study. They collaborated in protocol development and review, local IRB submission, data collection, and participated in drafting or review of the manuscript, and their names should be citable by PubMed.

Neonatal Kidney Collaborative

David T. Selewski, MD10, Subrata Sarkar, MD10, Alison Kent, MD11, Jeffery Fletcher, PhD11, Shahnaz Duara, MD2, Jennifer R. Charlton, MD12, Jonathan R. Swanson MD12, Ronnie Guillet, MD8, Carl D’Angio, MD8, Ayesa Mian, MD8, Deepak Kumar, MD4, Jennifer G. Jetton, MD13, Patrick D. Brophy, MD13, Tarah T. Colaizy, MD13, Jonathan M. Klein, MD13, Ayse Akcan Arikan, MD14, Christopher J. Rhee, MD14, Stuart L. Goldstein, MD15, Amy T. Nathan, MD15, Juan C. Kupferman, MD16, Alok Bhutada, MD16, Shantanu Rastogi, MD16, Elizabeth Bonachea, MD17, John Mahan, MD17, Alexandra Smith, MD18, Mamta Fuloria, MD19, Kimberly Reidy, MD19, Frederick J. Kaskel, MD19, Danielle E. Soranno, MD20, Jason Gien, MD20, Katja M. Gist, DO20, Aftab S. Chishti, MD21, Mina H. Hanna, MD21, Sangeeta Hingorani, MD22, Michelle Starr, MD22, Sunny Juul MD22, Craig S. Wong, MD23, Catherine Joseph, MD23, Tara DuPont, MD23, Robin Ohls, MD23, Amy Staples, MD23, Surender Khokhar, MD24, Mary Revenis, MD7, Sidharth K. Sethi, MD25, Smriri Rohatgi, MD25, Cherry Mammen, MD26, Anne Synnes, MDCM26, Sanjay Wazir, MD27, Pia Wintermark, MD28, Robert Woroniecki, MD29, Shanty Sridhar, MD29, Susan Ingraham, MD30, Arwa Nada, MD31

Funding

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, for the NKC steering committee annual meeting at the University of Alabama at Birmingham (UAB), as well as support for some of the AWAKEN investigators at UAB (L.B.J., R.J.G.). 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). Finally, 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). Funding sources for this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Author information

D.A. contributed to the conceptualization and design of the study, collected data, aided the data analysis, and drafted the initial manuscript. C.A., M.M., and M.Z. contributed to the conceptualization and design of the study, collected data, aided the data analysis, and revised the manuscript for critically important intellectual content. L.B. and R.G. completed the data analysis and interpretation, contributed to the drafting, and revised the manuscript for critically important intellectual content. R.R., J.D., T.K.D., P.R., S.P., .M.D., L.M., N.A., F.S.C., and E.R. contributed to the study design, collecting or supervising the collection of data, and revising the manuscript for critically important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work

Ethics Committee Approval

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

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: David J Askenazi serves on the speaker board for Baxter (Baxter, USA), and the Acute Kidney Injury (AKI) Foundation (Cincinnati, OH, USA); he also receives grant funding for studies not related to this manuscript from National Institutes of Health—National Institutes of Diabetes and Digestive and Kidney Diseases (NIH-NIDDK, R01 DK103608 and NIH-FDA, R01 FD005092). Jennifer G Jetton is supported by the University of Iowa Institute for Clinical and Translational Sciences NIH U54TR001356. Juan C. Kupferman is on the speaker’s Bureau and consultant for Alexion Pharmaceuticals. Robert Woroniecki is supported by the Department of Pediatrics at Stony Brook Children’s hospital (NY, USA). AWAKEN investigators at the Canberra Hospital were supported by the Canberra Hospital Private Practice fund, and investigators at University of Virginia Children’s Hospital were supported by a 100 Women Who Care Grant (100 Women Charitable Foundation, CA, USA).

Correspondence to David Askenazi.

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