Serum metabolic profile of postoperative acute kidney injury following infant cardiac surgery with cardiopulmonary bypass.

Jesse A Davidson, Benjamin S Frank, Tracy T Urban, Mark Twite, James Jaggers, Ludmila Khailova, Jelena Klawitter
Author Information
  1. Jesse A Davidson: Department of Pediatrics, Children's Hospital Colorado, University of Colorado, Aurora, CO, USA. jesse.davidson@childrenscolorado.org. ORCID
  2. Benjamin S Frank: Department of Pediatrics, Children's Hospital Colorado, University of Colorado, Aurora, CO, USA.
  3. Tracy T Urban: Children's Hospital Colorado Research Institute, Aurora, CO, USA.
  4. Mark Twite: Department of Anesthesiology, University of Colorado, Aurora, CO, USA.
  5. James Jaggers: Department of Surgery, University of Colorado, Aurora, CO, USA.
  6. Ludmila Khailova: Department of Pediatrics, Children's Hospital Colorado, University of Colorado, Aurora, CO, USA.
  7. Jelena Klawitter: Department of Anesthesiology, 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.

Keywords

References

  1. J Am Heart Assoc. 2019 Dec 3;8(23):e013130 [PMID: 31752638]
  2. Kidney Int. 2009 Oct;76(8):885-92 [PMID: 19641482]
  3. Nat Protoc. 2012 Apr 12;7(5):872-81 [PMID: 22498707]
  4. Kidney Int. 2019 Mar;95(3):590-610 [PMID: 30709662]
  5. J Am Heart Assoc. 2018 Dec 18;7(24):e010711 [PMID: 30561257]
  6. Pediatr Nephrol. 2017 Sep;32(9):1509-1517 [PMID: 28361230]
  7. Circ Res. 2018 Apr 27;122(9):1238-1258 [PMID: 29700070]
  8. PLoS One. 2016 Sep 22;11(9):e0163021 [PMID: 27657885]
  9. Mol Cell Biochem. 2014 Aug;393(1-2):123-31 [PMID: 24740757]
  10. Inflammation. 2014 Feb;37(1):223-34 [PMID: 24043287]
  11. Nephrol Dial Transplant. 2015 Oct;30(10):1630-8 [PMID: 25829324]
  12. Front Immunol. 2018 Jan 10;8:1957 [PMID: 29379504]
  13. Nat Rev Nephrol. 2020 Feb;16(2):99-111 [PMID: 31673160]
  14. Crit Care Med. 2015 Jul;43(7):1467-76 [PMID: 25844698]
  15. Front Mol Biosci. 2019 Dec 20;6:152 [PMID: 31921892]
  16. Metabolites. 2019 Feb 14;9(2): [PMID: 30769897]
  17. Sci Rep. 2018 Jun 4;8(1):8539 [PMID: 29867102]
  18. J Am Coll Cardiol. 2014 Dec 30;64(25):2753-62 [PMID: 25541128]
  19. Curr Opin Crit Care. 2014 Dec;20(6):613-9 [PMID: 25259720]
  20. BMC Nephrol. 2018 Feb 26;19(1):44 [PMID: 29482511]
  21. J Proteome Res. 2015 Jul 2;14(7):2897-905 [PMID: 26036910]
  22. Exp Mol Med. 2019 Feb 13;51(2):1-14 [PMID: 30760699]
  23. Nat Rev Mol Cell Biol. 2016 Jul;17(7):451-9 [PMID: 26979502]
  24. J Am Coll Cardiol. 2011 Nov 22;58(22):2301-9 [PMID: 22093507]
  25. PLoS One. 2014 Sep 05;9(9):e106647 [PMID: 25191961]
  26. Am J Physiol Renal Physiol. 2019 Jan 1;316(1):F54-F62 [PMID: 30379100]
  27. Lancet Child Adolesc Health. 2017 Nov;1(3):184-194 [PMID: 29732396]
  28. Front Pediatr. 2020 Jan 14;7:553 [PMID: 32010651]
  29. J Pharm Biomed Anal. 2015 Sep 10;113:108-20 [PMID: 25577715]
  30. Free Radic Res. 2013 Mar;47(3):233-40 [PMID: 23297832]
  31. Semin Vasc Med. 2005 May;5(2):201-8 [PMID: 16047272]
  32. J Pediatr. 2017 Nov;190:49-55.e2 [PMID: 29144270]
  33. Metabolomics. 2019 Oct 28;15(11):145 [PMID: 31659512]
  34. Ren Fail. 2015 Feb;37(1):96-102 [PMID: 25347234]
  35. Nephron. 2017;137(4):253-255 [PMID: 28591759]
  36. Physiol Rep. 2014 Dec 24;2(12): [PMID: 25539831]
  37. Biomed Chromatogr. 2016 Jan;30(1):13-28 [PMID: 26053056]
  38. Clin Biochem. 2016 Sep;49(13-14):955-61 [PMID: 27288551]
  39. JAMA Pediatr. 2016 Nov 1;170(11):1071-1078 [PMID: 27618162]
  40. Nucleic Acids Res. 2018 Jul 2;46(W1):W486-W494 [PMID: 29762782]
  41. Organogenesis. 2013 Jan-Mar;9(1):11-8 [PMID: 23538740]
  42. Lancet. 2005 Apr 2-8;365(9466):1231-8 [PMID: 15811456]
  43. J Pharmacokinet Biopharm. 1984 Feb;12(1):23-42 [PMID: 6235362]
  44. Hypertension. 2012 Apr;59(4):825-32 [PMID: 22353616]
  45. BMC Nephrol. 2017 Oct 31;18(1):326 [PMID: 29089036]
  46. Crit Care Med. 2011 Jun;39(6):1493-9 [PMID: 21336114]
  47. JCI Insight. 2019 Nov 14;4(22): [PMID: 31723053]
  48. J Nutr Sci Vitaminol (Tokyo). 2018;64(2):90-98 [PMID: 29710037]
  49. Anal Biochem. 2010 Jul 15;402(2):191-3 [PMID: 20361921]
  50. Metabolomics. 2020 Sep 5;16(9):93 [PMID: 32889608]
  51. J Thorac Cardiovasc Surg. 2012 Feb;143(2):368-74 [PMID: 21798562]
  52. J Pediatr. 2013 Jan;162(1):120-7.e1 [PMID: 22878115]
  53. Semin Nephrol. 2018 Jan;38(1):63-87 [PMID: 29291763]

Grants

  1. 13CRP17300016/American Heart Association-American Stroke Association
  2. K23 HL123634/NHLBI NIH HHS
  3. UL1 TR001082/NCATS NIH HHS
  4. UL1 TR002535/NCATS NIH HHS

MeSH Term

Acute Kidney Injury
Cardiac Surgical Procedures
Cardiopulmonary Bypass
Humans
Infant
Kynurenine
Metabolome
Methionine
Niacinamide
Postoperative Complications
Purines

Chemicals

Purines
Niacinamide
Kynurenine
Methionine

Word Cloud

Created with Highcharts 10.0.0AKIinfantsmetabolicprofile24-hserumstagedifferenceswithoutinjurysurgeryanalysispreoperativemetabolitesmetabolismchangesdetermineacutekidneyfollowingcardiopulmonarybypassCPBperformedpostoperativesamplesprofilesdeveloped1severegroupspurinemethioninekynurenine/nicotinamideinfantcardiacBACKGROUND:soughtcirculatingcardiothoracicMETHODS:secondary120daysoldundergoingMetabolicprofilingtargeted165viatandemmassspectrometrycompareddevelopfirst72hpostoperativelyglobaladditionspecificindividualRESULTS:total57includedstudySix11%KDIGO2/31323%differentiateInfantsmoderatelydistinguishedsegregatedtwooverlappingeitherDifferencesdriven21significantadjustedfalsediscoveryrate<005ProminentlyalteredpathwaysincludeCONCLUSION:Moderate-to-severeassociatedmetabolomeincludingprominentportionmilddemonstratedsimilarsuggestingpotentialroleevaluationlowerSerumCongenitalheartdiseaseHomocysteineKynurenicacidMetabolomicsNicotinamidePurine

Similar Articles

Cited By (8)