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.
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.
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.
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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Wong, J. H. et al. Severe acute kidney injury following stage 1 Norwood palliation: effect on outcomes and risk of severe acute kidney injury at subsequent surgical stages. Pediatr. Crit. Care. Med. 17, 615–623 (2016).
Taylor, M. L. et al. Mild postoperative acute kidney injury and outcomes after surgery for congenital heart disease. J. Thorac. Cardiovasc. Surg. 146, 146–152 (2013).
dos Santos El Halal, M. G. & Carvalho, P. R. Acute kidney injury according to pediatric RIFLE criteria is associated with negative outcomes after heart surgery in children. Pediatr. Nephrol. 28, 1307–1314 (2013).
Aydin, S. I. et al. Acute kidney injury after surgery for congenital heart disease. Ann. Thorac. Surg. 94, 1589–1595 (2012).
Mathur, N. B., Agarwal, H. S. & Maria, A. Acute renal failure in neonatal sepsis. Indian J. Pediatr. 73, 499–502 (2006).
Sarkar, S. et al. Relationship between acute kidney injury and brain MRI findings in asphyxiated newborns after therapeutic hypothermia. Pediatr. Res. 75, 431–435 (2014).
Alaro, D., Bashir, A., Musoke, R. & Wanaiana, L. Prevalence and outcomes of acute kidney injury in term neonates with perinatal asphyxia. Afr. Health Sci. 14, 682–688 (2014).
Selewski, D. T., Jordan, B. K., Askenazi, D. J., Dechert, R. E. & Sarkar, S. Acute kidney injury in asphyxiated newborns treated with therapeutic hypothermia. J. Pediatr. 162, 725–729 e721 (2013).
Askenazi, D. J. et al. Fluid overload and mortality are associated with acute kidney injury in sick near-term/term neonate. Pediatr. Nephrol. 28, 661–666 (2013).
Fleming, G. M. et al. The incidence of acute kidney injury and its effect on neonatal and pediatric extracorporeal membrane oxygenation outcomes: a multicenter report from the kidney intervention during extracorporeal membrane oxygenation study group. Pediatr. Crit. Care. Med. 17, 1157–1169 (2016).
Gadepalli, S. K., Selewski, D. T., Drongowski, R. A. & Mychaliska, G. B. Acute kidney injury in congenital diaphragmatic hernia requiring extracorporeal life support: an insidious problem. J. Pediatr. Surg. 46, 630–635 (2011).
Askenazi, D. J. et al. Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and pediatric noncardiac patients on extracorporeal membrane oxygenation. Pediatr. Crit. Care. Med. 12, e1–e6 (2011).
Askenazi, D. J., Griffin, R., McGwin, G., Carlo, W. & Ambalavanan, N. Acute kidney injury is independently associated with mortality in very low birthweight infants: a matched case-control analysis. Pediatr. Nephrol. 24, 991–997 (2009).
Carmody, J. B., Swanson, J. R., Rhone, E. T. & Charlton, J. R. Recognition and reporting of AKI in very low birth weight infants. Clin. J. Am. Soc. Nephrol. 9, 2036–2043 (2014).
Daga, A., Dapaah-Siakwan, F., Rajbhandari, S., Arevalo, C. & Salvador, A. Diagnosis and risk factors of acute kidney injury in very low birth weight infants. Pediatr. Neonatol. 58, 258–263 (2017).
Koralkar, R. et al. Acute kidney injury reduces survival in very low birth weight infants. Pediatr. Res. 69, 354–358 (2011).
Nagaraj, N., Berwal, P. K., Srinivas, A. & Berwal, A. A study of acute kidney injury in hospitalized preterm neonates in NICU. J. Neonatal Perinat. Med 9, 417–421 (2016).
Stojanovic, V., Barisic, N., Milanovic, B. & Doronjski, A. Acute kidney injury in preterm infants admitted to a neonatal intensive care unit. Pediatr. Nephrol. 29, 2213–2220 (2014).
Viswanathan, S., Manyam, B., Azhibekov, T. & Mhanna, M. J. Risk factors associated with acute kidney injury in extremely low birth weight (ELBW) infants. Pediatr. Nephrol. 27, 303–311 (2012).
Jetton, J. G. et al. Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates: design of a retrospective cohort study. Front. Pediatr. 4, 68 (2016).
Jetton, J. G. et al. Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. Lancet.: Child Adolesc. Health 1, 184–194 (2017).
Zappitelli, M. et al. Developing a neonatal acute kidney injury research definition: a report from the NIDDK neonatal AKI workshop. Pediatr. Res. 82, 569–573 (2017).
DeLong, E. R., DeLong, D. M. & Clarke-Pearson, D. L. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44, 837–845 (1988).
Trajman, A. & Luiz, R. R. McNemar chi2 test revisited: comparing sensitivity and specificity of diagnostic examinations. Scand. J. Clin. Lab. Invest. 68, 77–80 (2008).
Kellum, J. A., . & Lameire, N. KDIGO AKI Guideline Work Group Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1).Crit. Care 17, 204 (2013).
Askenazi, D. J., Ambalavanan, N. & Goldstein, S. L. Acute kidney injury in critically ill newborns: what do we know? What do we need to learn? Pediatr. Nephrol. 24, 265–274 (2009).
Gupta, C., Massaro, A. N. & Ray, P. E. A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy. Pediatr. Nephrol. 31, 1167–1178 (2016).
Askenazi, D., Saeidi, B., Koralkar, R., Ambalavanan, N. & Griffin, R. L. Acute changes in fluid status affect the incidence, associative clinical outcomes, and urine biomarker performance in premature infants with acute kidney injury. Pediatr. Nephrol. 31, 843–851 (2016).
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
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.