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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-07-01
|
Series: | Frontiers in Molecular Biosciences |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.665661/full |
_version_ | 1819112803389145088 |
---|---|
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. |
first_indexed | 2024-12-22T04:19:19Z |
format | Article |
id | doaj.art-4edc3199871c49d39550387fd21b9ead |
institution | Directory Open Access Journal |
issn | 2296-889X |
language | English |
last_indexed | 2024-12-22T04:19:19Z |
publishDate | 2021-07-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Molecular Biosciences |
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 |
work_keys_str_mv | AT szymonmacioszek comprehensivemetabolicsignatureofrenaldysplasiainchildrenamultiplatformmetabolomicsconcept AT renatawawrzyniak comprehensivemetabolicsignatureofrenaldysplasiainchildrenamultiplatformmetabolomicsconcept AT annakranz comprehensivemetabolicsignatureofrenaldysplasiainchildrenamultiplatformmetabolomicsconcept AT martakordalewska comprehensivemetabolicsignatureofrenaldysplasiainchildrenamultiplatformmetabolomicsconcept AT wiktoriastrucklewicka comprehensivemetabolicsignatureofrenaldysplasiainchildrenamultiplatformmetabolomicsconcept AT danutadudzik comprehensivemetabolicsignatureofrenaldysplasiainchildrenamultiplatformmetabolomicsconcept AT margotbiesemans comprehensivemetabolicsignatureofrenaldysplasiainchildrenamultiplatformmetabolomicsconcept AT michałmaternik comprehensivemetabolicsignatureofrenaldysplasiainchildrenamultiplatformmetabolomicsconcept AT aleksandramzurowska comprehensivemetabolicsignatureofrenaldysplasiainchildrenamultiplatformmetabolomicsconcept AT michałjmarkuszewski comprehensivemetabolicsignatureofrenaldysplasiainchildrenamultiplatformmetabolomicsconcept |