Incidence, Risk Factors, and Outcomes Associated With Recurrent Neonatal Acute Kidney Injury in the AWAKEN Study
Authors: Rutledge Austin D. , Griffin Russell L. , Vincent Katherine , Askenazi David J. , Segar Jeffrey L. , Kupferman Juan C. , Rastogi Shantanu , Selewski David T. , Steflik Heidi J. ,   Neonatal Kidney Collaborative, Sarkar Subrata , Kent Alison , Fletcher Jeffery , Charlton Jennifer R. , Swanson Jonathan R. , Abitbol Carolyn L. , DeFreitas Marissa , Duara Shahnaz , Guillet Ronnie , D’Angio Carl , Mian Ayesa , Rademacher Erin , Mhanna Maroun J. , Raina Rupesh , Kumar Deepak , Ambalavanan Namasivayam , Arikan Ayse A. , Rhee Christopher J. , Goldstein Stuart L. , Nathan Amy T. , Bhutada Alok , Bonachea Elizabeth , Ingraham Susan , Mahan John , Nada Arwa , Jetton Jennifer , Brophy Patrick D. , Colaizy Tarah T. , Klein Jonathan M. , Cole F. Sessions , Davis T. Keefe , Dower Joshua , Milner Lawrence , Smith Alexandra , Fuloria Mamta , Reidy Kimberly , Kaskel Frederick J. , Soranno Danielle E. , Gien Jason , Gist Katja M. , Hanna Mina H. , Chishti Aftab S. , Hingorani Sangeeta , Juul Sandra , Starr Michelle C. , Wong Craig S. , Joseph Catherine , DuPont Tara , Ohls Robin , Staples Amy , Rohatgi Smriti , Sethi Sidharth K. , Wazir Sanjay , Khokhar Surender , Perazzo Sofia , Ray Patricio E. , Revenis Mary , Mammen Cherry , Synnes Anne , Wintermark Pia , Zappitelli Michael , Woroniecki Robert , Sridhar Shanthy 
Published: February 2024

ImportanceThe incidence and associated outcomes of recurrent acute kidney injury (rAKI) in neonates remain largely unknown.ObjectiveTo determine the incidence, risk factors, and clinical outcomes associated with rAKI in critically ill neonates.Design, Setting, and ParticipantsThis cohort study was a secondary analysis of the multicenter, international Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates retrospective study. Comparisons were made among neonates with no AKI, a single AKI episode (sAKI), and rAKI. All neonates younger than 14 days who were admitted between January 1 and March 31, 2014, to 24 participating level II to IV neonatal intensive care units and received intravenous fluids for at least 48 hours were considered for inclusion. Neonates with congenital heart disease requiring surgery within the first week of life, lethal chromosomal anomalies, death within 48 hours of admission, or severe congenital kidney abnormalities were excluded. Data were analyzed from May 23, 2022, to December 8, 2023.ExposureRecurrent AKI using the neonatal Kidney Disease: Improving Global Outcomes criteria. Determination of each rAKI required a complete return to the baseline serum creatinine level that defined the prior AKI episode.Main Outcomes and MeasuresIncidence and risk factors of rAKI and associations of rAKI with length of stay (LOS; ie, birth to hospital discharge) and mortality.ResultsThe study cohort (n = 2162) included 1233 male neonates (57.0%). Gestational age distribution was less than 29 weeks for 276 neonates (12.8%), 29 to less than 36 weeks for 958 (44.3%), and 36 weeks or older for 928 (42.9%). Of 605 neonates with AKI, 133 (22.0%) developed rAKI with risk factors including younger gestational age, lower birthweight, and higher stage of initial AKI. Infants with rAKI experienced longer median LOS (no AKI, 17 [IQR, 8-34] days; sAKI, 18 [IQR, 9-45] days; rAKI, 60 [IQR, 25-109] days; P &amp;lt; .001). Time-varying Cox proportional hazards regression models suggest rAKI is independently associated with a lower hazard of discharge (adjusted hazard ratio, 0.7 [95% CI, 0.6-0.9]; P = .01) when compared with sAKI, but mortality did not differ between groups (adjusted hazard ratio, 1.4 [95% CI, 0.6-3.0]; P = .44).Conclusions and RelevanceIn this cohort study, neonatal rAKI was independently associated with longer LOS when compared with sAKI, suggesting that rAKI in neonates may be an important clinical distinction warranting further study and careful monitoring after an initial AKI episode.