Kelly Mercier1, Susan McRitchie1, Wimal Pathmasiri1, Andrew Novokhatny1, Rajesh Koralkar2, David Askenazi2, Patrick D Brophy3, Susan Sumner4. 1. RTI International, 3040 E. Cornwallis Road, Research Triangle Park, Triangle, NC, 27709, USA. 2. University of Alabama Children's Hospital, Birmingham, AL, USA. 3. University of Iowa Children's Hospital, 1269A-CBRB Newton Road, Iowa City, IA, 52242, USA. brophy@uihealthsystem.org. 4. RTI International, 3040 E. Cornwallis Road, Research Triangle Park, Triangle, NC, 27709, USA. ssumner@rti.org.
Abstract
BACKGROUND: Acute kidney injury (AKI) staging has been developed in the adult and pediatric populations, but these do not yet exist for the neonatal population. Metabolomics was utilized to uncover biomarkers of normal and AKI-associated renal function in preterm infants. The study comprised 20 preterm infants with an AKI diagnosis who were matched by gestational age and gender to 20 infants without an AKI diagnosis. METHODS: Urine samples from pre-term newborn infants collected on day 2 of life were analyzed using broad-spectrum nuclear magnetic resonance (NMR) metabolomics. Multivariate analysis methods were used to identify metabolite profiles that differentiated AKI and no AKI, and to identify a metabolomics profile correlating with gestational age in infants with and without AKI. RESULTS: There was a clear distinction between the AKI and no-AKI profiles. Two previously identified biomarkers of AKI, hippurate and homovanillate, differentiated AKI from no-AKI profiles. Pathway analysis revealed similarities to cholinergic neurons, prenatal nicotine exposure on pancreatic β cells, and amitraz-induced inhibition of insulin secretion. Additionally, a pH difference was noted. Both pH and the metabolites were found to be associated with AKI; however, only the metabotype was a significant predictor of AKI. Pathways for the no-AKI group that correlated uniquely with gestational age included aminoacyl-t-RNA biosynthesis, whereas pathways in the AKI group yielded potential metabolite changes in pyruvate metabolism. CONCLUSIONS: Metabolomics was able to differentiate the urinary profiles of neonates with and without an AKI diagnosis and metabolic developmental profiles correlated with gestational age. Further studies in larger cohorts are needed to validate these results.
BACKGROUND:Acute kidney injury (AKI) staging has been developed in the adult and pediatric populations, but these do not yet exist for the neonatal population. Metabolomics was utilized to uncover biomarkers of normal and AKI-associated renal function in preterm infants. The study comprised 20 preterm infants with an AKI diagnosis who were matched by gestational age and gender to 20 infants without an AKI diagnosis. METHODS: Urine samples from pre-term newborn infants collected on day 2 of life were analyzed using broad-spectrum nuclear magnetic resonance (NMR) metabolomics. Multivariate analysis methods were used to identify metabolite profiles that differentiated AKI and no AKI, and to identify a metabolomics profile correlating with gestational age in infants with and without AKI. RESULTS: There was a clear distinction between the AKI and no-AKI profiles. Two previously identified biomarkers of AKI, hippurate and homovanillate, differentiated AKI from no-AKI profiles. Pathway analysis revealed similarities to cholinergic neurons, prenatal nicotine exposure on pancreatic β cells, and amitraz-induced inhibition of insulin secretion. Additionally, a pH difference was noted. Both pH and the metabolites were found to be associated with AKI; however, only the metabotype was a significant predictor of AKI. Pathways for the no-AKI group that correlated uniquely with gestational age included aminoacyl-t-RNA biosynthesis, whereas pathways in the AKI group yielded potential metabolite changes in pyruvate metabolism. CONCLUSIONS: Metabolomics was able to differentiate the urinary profiles of neonates with and without an AKI diagnosis and metabolic developmental profiles correlated with gestational age. Further studies in larger cohorts are needed to validate these results.
Authors: Richard D Beger; Ricky D Holland; Jinchun Sun; Laura K Schnackenberg; Page C Moore; Catherine L Dent; Prasad Devarajan; Didier Portilla Journal: Pediatr Nephrol Date: 2008-06 Impact factor: 3.714
Authors: David S Wishart; Dan Tzur; Craig Knox; Roman Eisner; An Chi Guo; Nelson Young; Dean Cheng; Kevin Jewell; David Arndt; Summit Sawhney; Chris Fung; Lisa Nikolai; Mike Lewis; Marie-Aude Coutouly; Ian Forsythe; Peter Tang; Savita Shrivastava; Kevin Jeroncic; Paul Stothard; Godwin Amegbey; David Block; David D Hau; James Wagner; Jessica Miniaci; Melisa Clements; Mulu Gebremedhin; Natalie Guo; Ying Zhang; Gavin E Duggan; Glen D Macinnis; Alim M Weljie; Reza Dowlatabadi; Fiona Bamforth; Derrick Clive; Russ Greiner; Liang Li; Tom Marrie; Brian D Sykes; Hans J Vogel; Lori Querengesser Journal: Nucleic Acids Res Date: 2007-01 Impact factor: 16.971
Authors: David S Wishart; Craig Knox; An Chi Guo; Roman Eisner; Nelson Young; Bijaya Gautam; David D Hau; Nick Psychogios; Edison Dong; Souhaila Bouatra; Rupasri Mandal; Igor Sinelnikov; Jianguo Xia; Leslie Jia; Joseph A Cruz; Emilia Lim; Constance A Sobsey; Savita Shrivastava; Paul Huang; Philip Liu; Lydia Fang; Jun Peng; Ryan Fradette; Dean Cheng; Dan Tzur; Melisa Clements; Avalyn Lewis; Andrea De Souza; Azaret Zuniga; Margot Dawe; Yeping Xiong; Derrick Clive; Russ Greiner; Alsu Nazyrova; Rustem Shaykhutdinov; Liang Li; Hans J Vogel; Ian Forsythe Journal: Nucleic Acids Res Date: 2008-10-25 Impact factor: 16.971
Authors: Alexandra Franiek; Atul Sharma; Vedran Cockovski; David S Wishart; Michael Zappitelli; Tom D Blydt-Hansen Journal: Pediatr Nephrol Date: 2022-01-10 Impact factor: 3.651
Authors: Anshika Jain; Ryan Huang; Jasmine Lee; Natasha Jawa; Yong Jin Lim; Mike Guron; Sharon Abish; Paul C Boutros; Michael Brudno; Bruce Carleton; Geoffrey D E Cuvelier; Lakshman Gunaratnam; Cheryl Ho; Khosrow Adeli; Sara Kuruvilla; Giles Lajoie; Geoffrey Liu; Paul C Nathan; Shahrad Rod Rassekh; Michael Rieder; Sushrut S Waikar; Stephen A Welch; Matthew A Weir; Eric Winquist; David S Wishart; Alexandra P Zorzi; Tom Blydt-Hansen; Michael Zappitelli; Bradley Urquhart Journal: Can J Kidney Health Dis Date: 2021-11-17
Authors: Simona Riccio; Maria Sole Valentino; Antonio Paride Passaro; Marica Izzo; Stefano Guarino; Emanuele Miraglia Del Giudice; Pierluigi Marzuillo; Anna Di Sessa Journal: Children (Basel) Date: 2022-01-17
Authors: Nuria Esturau-Escofet; Eduardo Rodríguez de San Miguel; Marcela Vela-Amieva; Martha E García-Aguilera; Circe C Hernández-Espino; Luis Macias-Kauffer; Carlos López-Candiani; José J Naveja; Isabel Ibarra-González Journal: Metabolites Date: 2022-03-17