Urinary metabolomics to develop predictors for pediatric acute kidney injury. 2022

Alexandra Franiek, and Atul Sharma, and Vedran Cockovski, and David S Wishart, and Michael Zappitelli, and Tom D Blydt-Hansen
College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, Scotland.

Acute kidney injury (AKI) is characterized by an abrupt decline in glomerular filtration rate (GFR). We sought to identify separate early urinary metabolomic signatures at AKI onset (with-AKI) and prior to onset of functional impairment (pre-AKI). Pre-AKI (n=15), AKI (n=22), and respective controls (n=30) from two prospective PICU cohort studies provided urine samples which were analyzed by GC-MS and DI-MS mass spectrometry (193 metabolites). The cohort (n=58) was 8.7±6.4 years old and 66% male. AKI patients had longer PICU stays, higher PRISM scores, vasopressors requirement, and respiratory diagnosis and less commonly had trauma or post-operative diagnosis. Urine was collected within 2-3 days after admission and daily until day 5 or 14. The metabolite classifiers for pre-AKI samples (1.5±1.1 days prior to AKI onset) had a cross-validated area under receiver operator curve (AUC)=0.93 (95%CI 0.85-1.0); with-AKI samples had an AUC=0.94 (95%CI 0.87-1.0). A parsimonious pre-AKI classifier with 13 metabolites was similarly robust (AUC=0.96, 95%CI 0.89-1.0). Both classifiers were similar and showed modest correlation of high-ranking metabolites (tau=0.47, p<0.001). This exploratory study demonstrates the potential of a urine metabolite classifier to detect AKI-risk in pediatric populations earlier than the current standard of diagnosis with the need for external validation. A higher resolution version of the Graphical abstract is available as Supplementary information with inner reference to ESM for GA.

UI MeSH Term Description Entries
D008297 Male Males
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D005260 Female Females
D005919 Glomerular Filtration Rate The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance. Filtration Rate, Glomerular,Filtration Rates, Glomerular,Glomerular Filtration Rates,Rate, Glomerular Filtration,Rates, Glomerular Filtration
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D055432 Metabolomics The systematic identification and quantitation of all the metabolic products of a cell, tissue, organ, or organism under varying conditions. The METABOLOME of a cell or organism is a dynamic collection of metabolites which represent its net response to current conditions. Metabonomics,Metabolomic,Metabonomic

Related Publications

Alexandra Franiek, and Atul Sharma, and Vedran Cockovski, and David S Wishart, and Michael Zappitelli, and Tom D Blydt-Hansen
November 2021, Hepatology (Baltimore, Md.),
Alexandra Franiek, and Atul Sharma, and Vedran Cockovski, and David S Wishart, and Michael Zappitelli, and Tom D Blydt-Hansen
February 2011, Pediatric nephrology (Berlin, Germany),
Alexandra Franiek, and Atul Sharma, and Vedran Cockovski, and David S Wishart, and Michael Zappitelli, and Tom D Blydt-Hansen
December 2017, Pediatric nephrology (Berlin, Germany),
Alexandra Franiek, and Atul Sharma, and Vedran Cockovski, and David S Wishart, and Michael Zappitelli, and Tom D Blydt-Hansen
November 2018, Journal of the American College of Radiology : JACR,
Alexandra Franiek, and Atul Sharma, and Vedran Cockovski, and David S Wishart, and Michael Zappitelli, and Tom D Blydt-Hansen
January 2018, Contributions to nephrology,
Alexandra Franiek, and Atul Sharma, and Vedran Cockovski, and David S Wishart, and Michael Zappitelli, and Tom D Blydt-Hansen
January 2013, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences,
Alexandra Franiek, and Atul Sharma, and Vedran Cockovski, and David S Wishart, and Michael Zappitelli, and Tom D Blydt-Hansen
December 2016, Pediatric nephrology (Berlin, Germany),
Alexandra Franiek, and Atul Sharma, and Vedran Cockovski, and David S Wishart, and Michael Zappitelli, and Tom D Blydt-Hansen
February 2020, International journal of molecular sciences,
Alexandra Franiek, and Atul Sharma, and Vedran Cockovski, and David S Wishart, and Michael Zappitelli, and Tom D Blydt-Hansen
October 2018, Clinica chimica acta; international journal of clinical chemistry,
Alexandra Franiek, and Atul Sharma, and Vedran Cockovski, and David S Wishart, and Michael Zappitelli, and Tom D Blydt-Hansen
July 2022, International journal of antimicrobial agents,
Copied contents to your clipboard!