Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics Concept

Renal dysplasia is a severe congenital abnormality of the kidney parenchyma, which is an important cause of end-stage renal failure in childhood and early adulthood. The diagnosis of renal dysplasia relies on prenatal or postnatal ultrasounds as children show no specific clinical symptoms before chr...

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Main Authors: Szymon Macioszek, Renata Wawrzyniak, Anna Kranz, Marta Kordalewska, Wiktoria Struck-Lewicka, Danuta Dudzik, Margot Biesemans, Michał Maternik, Aleksandra M. Żurowska, Michał J. Markuszewski
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Molecular Biosciences
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Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2021.665661/full
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author Szymon Macioszek
Renata Wawrzyniak
Anna Kranz
Marta Kordalewska
Wiktoria Struck-Lewicka
Danuta Dudzik
Margot Biesemans
Michał Maternik
Aleksandra M. Żurowska
Michał J. Markuszewski
author_facet Szymon Macioszek
Renata Wawrzyniak
Anna Kranz
Marta Kordalewska
Wiktoria Struck-Lewicka
Danuta Dudzik
Margot Biesemans
Michał Maternik
Aleksandra M. Żurowska
Michał J. Markuszewski
author_sort Szymon Macioszek
collection DOAJ
description Renal dysplasia is a severe congenital abnormality of the kidney parenchyma, which is an important cause of end-stage renal failure in childhood and early adulthood. The diagnosis of renal dysplasia relies on prenatal or postnatal ultrasounds as children show no specific clinical symptoms before chronic kidney disease develops. Prompt diagnosis is important in terms of early introduction of nephroprotection therapy and improved long-term prognosis. Metabolomics was applied to study children with renal dysplasia to provide insight into the changes in biochemical pathways underlying its pathology and in search of early indicators for facilitated diagnosis. The studied cohort consisted of 72 children, 39 with dysplastic kidneys and 33 healthy controls. All subjects underwent comprehensive urine metabolic profiling with the use of gas chromatography and liquid chromatography coupled to mass spectrometry, with two complementary separation modes of the latter. Univariate and multivariate statistical calculations identified a total of nineteen metabolites, differentiating the compared cohorts, independent of their estimated glomerular filtration rate. Seven acylcarnitines, xanthine, and glutamine were downregulated in the urine of renal dysplasia patients. Conversely, renal dysplasia was associated with higher urinary levels of dimethylguanosine, threonic acid or glyceric acid. This is the first metabolomic study of subjects with renal dysplasia. The authors define a characteristic urine metabolic signature in children with dysplastic kidneys, irrespective of renal function, linking the condition with altered fatty acid oxidation, amino acid and purine metabolisms.
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spelling doaj.art-4edc3199871c49d39550387fd21b9ead2022-12-21T18:39:20ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-07-01810.3389/fmolb.2021.665661665661Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics ConceptSzymon Macioszek0Renata Wawrzyniak1Anna Kranz2Marta Kordalewska3Wiktoria Struck-Lewicka4Danuta Dudzik5Margot Biesemans6Michał Maternik7Aleksandra M. Żurowska8Michał J. Markuszewski9Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, PolandDepartment of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, PolandDepartment of Pediatrics, Nephrology and Hypertension, Medical University of Gdańsk, Gdańsk, PolandDepartment of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, PolandDepartment of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, PolandDepartment of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, PolandDepartment of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, PolandDepartment of Pediatrics, Nephrology and Hypertension, Medical University of Gdańsk, Gdańsk, PolandCentre for Rare Diseases, Medical University of Gdańsk, Gdańsk, PolandDepartment of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, PolandRenal dysplasia is a severe congenital abnormality of the kidney parenchyma, which is an important cause of end-stage renal failure in childhood and early adulthood. The diagnosis of renal dysplasia relies on prenatal or postnatal ultrasounds as children show no specific clinical symptoms before chronic kidney disease develops. Prompt diagnosis is important in terms of early introduction of nephroprotection therapy and improved long-term prognosis. Metabolomics was applied to study children with renal dysplasia to provide insight into the changes in biochemical pathways underlying its pathology and in search of early indicators for facilitated diagnosis. The studied cohort consisted of 72 children, 39 with dysplastic kidneys and 33 healthy controls. All subjects underwent comprehensive urine metabolic profiling with the use of gas chromatography and liquid chromatography coupled to mass spectrometry, with two complementary separation modes of the latter. Univariate and multivariate statistical calculations identified a total of nineteen metabolites, differentiating the compared cohorts, independent of their estimated glomerular filtration rate. Seven acylcarnitines, xanthine, and glutamine were downregulated in the urine of renal dysplasia patients. Conversely, renal dysplasia was associated with higher urinary levels of dimethylguanosine, threonic acid or glyceric acid. This is the first metabolomic study of subjects with renal dysplasia. The authors define a characteristic urine metabolic signature in children with dysplastic kidneys, irrespective of renal function, linking the condition with altered fatty acid oxidation, amino acid and purine metabolisms.https://www.frontiersin.org/articles/10.3389/fmolb.2021.665661/fullrenal dysplasiametabolomicspediatric nephrologymultiplatform approachesLC-MSGC-MS
spellingShingle Szymon Macioszek
Renata Wawrzyniak
Anna Kranz
Marta Kordalewska
Wiktoria Struck-Lewicka
Danuta Dudzik
Margot Biesemans
Michał Maternik
Aleksandra M. Żurowska
Michał J. Markuszewski
Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics Concept
Frontiers in Molecular Biosciences
renal dysplasia
metabolomics
pediatric nephrology
multiplatform approaches
LC-MS
GC-MS
title Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics Concept
title_full Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics Concept
title_fullStr Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics Concept
title_full_unstemmed Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics Concept
title_short Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics Concept
title_sort comprehensive metabolic signature of renal dysplasia in children a multiplatform metabolomics concept
topic renal dysplasia
metabolomics
pediatric nephrology
multiplatform approaches
LC-MS
GC-MS
url https://www.frontiersin.org/articles/10.3389/fmolb.2021.665661/full
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