Metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease. Although children with ADPKD show normal renal function, cyst development is already occurring. In this study, we aimed to identify markers and associated molecular pathways of disease progre...

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Autores principales:	Madhurima M. Baliga, Jost Klawitter, Uwe Christians, Katharina Hopp, Michel Chonchol, Berenice Y. Gitomer, Melissa A. Cadnapaphornchai, Jelena Klawitter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ed732939e4254c12b38eee6288ac56ec
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spelling	oai:doaj.org-article:ed732939e4254c12b38eee6288ac56ec2021-12-02T17:04:35ZMetabolic profiling in children and young adults with autosomal dominant polycystic kidney disease10.1038/s41598-021-84609-82045-2322https://doaj.org/article/ed732939e4254c12b38eee6288ac56ec2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84609-8https://doaj.org/toc/2045-2322Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease. Although children with ADPKD show normal renal function, cyst development is already occurring. In this study, we aimed to identify markers and associated molecular pathways of disease progression in children and young adults with ADPKD. Plasma samples were collected during a 3-year randomized, double-blind, placebo-controlled, phase III clinical trial that was designed to test the efficacy of pravastatin on slowing down ADPKD progression in pediatric patients. Samples from 58 patients were available at baseline and at the 3-year endpoint of the study, respectively. Furthermore, plasma samples from 98 healthy children were used as controls. Metabolomic analysis was performed using liquid chromatography-tandem mass spectrometry and differences in metabolic profiles over time and within study groups were evaluated. While pravastatin therapy led to a decrease in a percent change of total kidney volume (HtTKV) in ADPKD patients, it had minimal effects on metabolite changes. Oxidative stress, endothelial dysfunction, inflammation and immune response were the most affected signaling pathways that distinguished healthy from diseased children. Pathway analysis revealed that metabolites in the arginine metabolism (urea and nitric oxide cycles), asparagine and glutamine metabolism, in the methylation cycle and kynurenine pathway were significantly changed between healthy and children with ADPDK and continued to diverge from the control levels while the disease progressed. Detected metabolite changes were primarily governed by disease progression, and less by pravastatin treatment. Identified metabolic pathways, from arginine and asparagine to kynurenine metabolism could present therapeutic targets and should be further investigated for potential to treat ADPKD progression at an early stage.Madhurima M. BaligaJost KlawitterUwe ChristiansKatharina HoppMichel ChoncholBerenice Y. GitomerMelissa A. CadnapaphornchaiJelena KlawitterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Madhurima M. Baliga Jost Klawitter Uwe Christians Katharina Hopp Michel Chonchol Berenice Y. Gitomer Melissa A. Cadnapaphornchai Jelena Klawitter Metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease
description	Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease. Although children with ADPKD show normal renal function, cyst development is already occurring. In this study, we aimed to identify markers and associated molecular pathways of disease progression in children and young adults with ADPKD. Plasma samples were collected during a 3-year randomized, double-blind, placebo-controlled, phase III clinical trial that was designed to test the efficacy of pravastatin on slowing down ADPKD progression in pediatric patients. Samples from 58 patients were available at baseline and at the 3-year endpoint of the study, respectively. Furthermore, plasma samples from 98 healthy children were used as controls. Metabolomic analysis was performed using liquid chromatography-tandem mass spectrometry and differences in metabolic profiles over time and within study groups were evaluated. While pravastatin therapy led to a decrease in a percent change of total kidney volume (HtTKV) in ADPKD patients, it had minimal effects on metabolite changes. Oxidative stress, endothelial dysfunction, inflammation and immune response were the most affected signaling pathways that distinguished healthy from diseased children. Pathway analysis revealed that metabolites in the arginine metabolism (urea and nitric oxide cycles), asparagine and glutamine metabolism, in the methylation cycle and kynurenine pathway were significantly changed between healthy and children with ADPDK and continued to diverge from the control levels while the disease progressed. Detected metabolite changes were primarily governed by disease progression, and less by pravastatin treatment. Identified metabolic pathways, from arginine and asparagine to kynurenine metabolism could present therapeutic targets and should be further investigated for potential to treat ADPKD progression at an early stage.
format	article
author	Madhurima M. Baliga Jost Klawitter Uwe Christians Katharina Hopp Michel Chonchol Berenice Y. Gitomer Melissa A. Cadnapaphornchai Jelena Klawitter
author_facet	Madhurima M. Baliga Jost Klawitter Uwe Christians Katharina Hopp Michel Chonchol Berenice Y. Gitomer Melissa A. Cadnapaphornchai Jelena Klawitter
author_sort	Madhurima M. Baliga
title	Metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease
title_short	Metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease
title_full	Metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease
title_fullStr	Metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease
title_full_unstemmed	Metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease
title_sort	metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ed732939e4254c12b38eee6288ac56ec
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Metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease

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