Jesse A Davidson1, Benjamin S Frank2, Tracy T Urban3, Mark Twite4, James Jaggers5, Ludmila Khailova2, Jelena Klawitter4,6. 1. Department of Pediatrics, Children's Hospital Colorado, University of Colorado, Aurora, CO, USA. jesse.davidson@childrenscolorado.org. 2. Department of Pediatrics, Children's Hospital Colorado, University of Colorado, Aurora, CO, USA. 3. Children's Hospital Colorado Research Institute, Aurora, CO, USA. 4. Department of Anesthesiology, University of Colorado, Aurora, CO, USA. 5. Department of Surgery, University of Colorado, Aurora, CO, USA. 6. Division of Renal Diseases and Hypertension, University of Colorado, Aurora, CO, USA.
Abstract
BACKGROUND: We sought to determine differences in the circulating metabolic profile of infants with or without acute kidney injury (AKI) following cardiothoracic surgery with cardiopulmonary bypass (CPB). METHODS: We performed a secondary analysis of preoperative and 24-h postoperative serum samples from infants ≤ 120 days old undergoing CPB. Metabolic profiling of the serum samples was performed by targeted analysis of 165 serum metabolites via tandem mass spectrometry. We then compared infants who did or did not develop AKI in the first 72 h postoperatively to determine global differences in the preoperative and 24-h metabolic profiles in addition to specific differences in individual metabolites. RESULTS: A total of 57 infants were included in the study. Six infants (11%) developed KDIGO stage 2/3 AKI and 13 (23%) developed stage 1 AKI. The preoperative metabolic profile did not differentiate between infants with or without AKI. Infants with severe AKI could be moderately distinguished from infants without AKI by their 24-h metabolic profile, while infants with stage 1 AKI segregated into two groups, overlapping with either the no AKI or severe AKI groups. Differences in these 24-h metabolic profiles were driven by 21 metabolites significant at an adjusted false discovery rate of < 0.05. Prominently altered pathways include purine, methionine, and kynurenine/nicotinamide metabolism. CONCLUSION: Moderate-to-severe AKI after infant cardiac surgery is associated with changes in the serum metabolome, including prominent changes to purine, methionine, and kynurenine/nicotinamide metabolism. A portion of infants with mild AKI demonstrated similar metabolic changes, suggesting a potential role for metabolic analysis in the evaluation of lower stage injury.
BACKGROUND: We sought to determine differences in the circulating metabolic profile of infants with or without acute kidney injury (AKI) following cardiothoracic surgery with cardiopulmonary bypass (CPB). METHODS: We performed a secondary analysis of preoperative and 24-h postoperative serum samples from infants ≤ 120 days old undergoing CPB. Metabolic profiling of the serum samples was performed by targeted analysis of 165 serum metabolites via tandem mass spectrometry. We then compared infants who did or did not develop AKI in the first 72 h postoperatively to determine global differences in the preoperative and 24-h metabolic profiles in addition to specific differences in individual metabolites. RESULTS: A total of 57 infants were included in the study. Six infants (11%) developed KDIGO stage 2/3 AKI and 13 (23%) developed stage 1 AKI. The preoperative metabolic profile did not differentiate between infants with or without AKI. Infants with severe AKI could be moderately distinguished from infants without AKI by their 24-h metabolic profile, while infants with stage 1 AKI segregated into two groups, overlapping with either the no AKI or severe AKI groups. Differences in these 24-h metabolic profiles were driven by 21 metabolites significant at an adjusted false discovery rate of < 0.05. Prominently altered pathways include purine, methionine, and kynurenine/nicotinamide metabolism. CONCLUSION: Moderate-to-severe AKI after infant cardiac surgery is associated with changes in the serum metabolome, including prominent changes to purine, methionine, and kynurenine/nicotinamide metabolism. A portion of infants with mild AKI demonstrated similar metabolic changes, suggesting a potential role for metabolic analysis in the evaluation of lower stage injury.
Authors: Robert W McGarrah; Scott B Crown; Guo-Fang Zhang; Svati H Shah; Christopher B Newgard Journal: Circ Res Date: 2018-04-27 Impact factor: 17.367
Authors: Benjamin M Fox; Hyo-Wook Gil; Lara Kirkbride-Romeo; Rushita A Bagchi; Sara A Wennersten; Korey R Haefner; Nataliya I Skrypnyk; Carolyn N Brown; Danielle E Soranno; Katja M Gist; Benjamin R Griffin; Anna Jovanovich; Julie A Reisz; Matthew J Wither; Angelo D'Alessandro; Charles L Edelstein; Nathan Clendenen; Timothy A McKinsey; Christopher Altmann; Sarah Faubel Journal: Kidney Int Date: 2019-01-30 Impact factor: 10.612
Authors: Michael Zappitelli; Pierre-Luc Bernier; Richard S Saczkowski; Christo I Tchervenkov; Ronald Gottesman; Adrian Dancea; Ayaz Hyder; Omar Alkandari Journal: Kidney Int Date: 2009-07-29 Impact factor: 10.612
Authors: Jesse A Davidson; Zachary Pfeifer; Benjamin Frank; Suhong Tong; Tracy T Urban; Paul A Wischmeyer; Peter Mourani; Bruce Landeck; Uwe Christians; Jelena Klawitter Journal: J Am Heart Assoc Date: 2018-12-18 Impact factor: 5.501
Authors: Wojciech Dabrowski; Tomasz Kocki; Jacek Pilat; Jolanta Parada-Turska; Manu L N G Malbrain Journal: Inflammation Date: 2014-02 Impact factor: 4.092
Authors: Benjamin De Becker; Catherine Coremans; Martin Chaumont; Cédric Delporte; Pierre Van Antwerpen; Thierry Franck; Alexandre Rousseau; Karim Zouaoui Boudjeltia; Pierre Cullus; Philippe van de Borne Journal: J Am Heart Assoc Date: 2019-11-22 Impact factor: 5.501
Authors: Jesse A Davidson; Justin Robison; Ludmila Khailova; Benjamin S Frank; James Jaggers; Richard J Ing; Scott Lawson; John Iguidbashian; Eiman Ali; Amy Treece; Danielle E Soranno; Suzanne Osorio-Lujan; Jelena Klawitter Journal: Am J Physiol Renal Physiol Date: 2022-05-09