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Age-related renal function decline: a comprehensive study using metabolomic analysis

Applicant Ponte Belén
Number 186203
Funding scheme Marie Heim-Voegtlin grants
Research institution Service de Néphrologie Département de Médecine Interne Hôpitaux Universitaires de Genève
Institution of higher education University of Geneva - GE
Main discipline Internal Medicine
Start/End 01.05.2019 - 31.10.2019
Approved amount 45'203.00
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All Disciplines (2)

Discipline
Internal Medicine
Methods of Epidemiology and Preventive Medicine

Keywords (5)

metabolomic; biomarkers; chronic kidney disease; ageing; renal function

Lay Summary (French)

Lead
Par le biais d'une étude de différentes populations, nous essayons de comprendre les mécanismes de la baisse de fonction liée à l'âge. Des profiles métabolomiques différents ont été mis en évidence selon le degré d'atteinte rénale. Certains métabolites semblent également prédire la détérioration de la fonction rénale au cours du temps. Le but du projet actuel est de comprendre les voies biologiques pouvant mener à l'identification de nouveaux marqueurs d'atteinte rénale.
Lay summary
Actuellement, la fonction rénale (FR) est estimée par des équations qui estiment le débit de filtration glomérulaire (DFG) en intégrant la créatinine sérique. L'insuffisance rénale chronique (IRC) est définie par un DFG<60ml/min. En utilisant cette valeur seuil, 50% des adultes > 70 ans ont une "maladie rénale chronique". Nous avons précédemment confirmé que 2/3 de la population générale présente une baisse de la FR au cours du temps. Nous avons également trouvé certains facteurs accélérant cette baisse comme la consommation de sel, ou l'hypertension. La question demeure si les personnes âgées présentent une réelle baisse de la FR ou une IRC, ou si il s'agit simplement d'une dégénérescence liée à l'âge sans signification clinique.
Nous avons donc étudier les profiles métabolomiques de différentes populations afin d'identifier des marqueurs associé au DFG. Nous avons mis en évidence plusieurs métabolites dans le sang ou les urines qui semblent prédire l'évolution de la fonction rénale. De plus le profile semble être différent selon le degré d'atteinte de la FR, et affecté également par l'épuration extrarénale. Les métabolites identifiés baissent ou augmentent avec la détérioration de la FR ou l'épuration.
Il nous reste encore  à déterminer si l'utilisation de la métabolomique permet de prédire et comprendre la baisse de FR liée à l'âge. Il faut également identifier les voies biologiques pouvant expliquer ces différences. Le but du projet actuel est de mieux caractériser les découvertes récentes et approfondir les analyses.


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Direct link to Lay Summary Last update: 24.04.2019

Responsible applicant and co-applicants

Employees

Publications

Publication
Parathyroid hormone and plasma phosphate are predictors of soluble α-klotho levels in adults of European descent
Dhayat Nasser A, Pruijm Menno, Ponte Belen, Ackermann Daniel, Leichtle Alexander Benedikt, Devuyst Olivier, Ehret Georg, Guessous Idris, Pechère-Bertschi Antoinette, Pastor Johanne, Martin Pierre-Yves, Burnier Michel, Fiedler Georg-Martin, Vogt Bruno, Moe Orson W, Bochud Murielle, Fuster Daniel G (2019), Parathyroid hormone and plasma phosphate are predictors of soluble α-klotho levels in adults of European descent, in The Journal of Clinical Endocrinology & Metabolism.
Dialysis initiation improves calcification propensity
Ponte Belen, Pruijm Menno, Pasch Andreas, Dufey-Teso Anne, Martin Pierre-Yves, de Seigneux Sophie (2019), Dialysis initiation improves calcification propensity, in Nephrology Dialysis Transplantation.
Renal Resistive Index Is Associated With Inactive Matrix Gla (γ-Carboxyglutamate) Protein in an Adult Population-Based Study.
(2019), Renal Resistive Index Is Associated With Inactive Matrix Gla (γ-Carboxyglutamate) Protein in an Adult Population-Based Study., in Journal of American Heart Association, e013558.
Combining the advantages of multilevel and orthogonal partial least squares data analysis for longitudinal metabolomics: Application to kidney transplantation.
GagnebinYoric, PezzatiJulien, LescuyerPierre, BroccardJulien, Ponte*Belen, RudazSerge, Combining the advantages of multilevel and orthogonal partial least squares data analysis for longitudinal metabolomics: Application to kidney transplantation., in Anal Chim Acta, 26.

Collaboration

Group / person Country
Types of collaboration
Prof O Devuyst, Institute of Physiology, University of Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof P Vollenweider - Service de Médecine Interne - Centre Hospitalier Universitaire Vaudois (CHUV) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof Sven Bergmann - Département of Computonal Biology - University of Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof J Staessen Department of Cardiovascular Diseases, University of Leuven Belgium (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof M Bochud, Z Kutalik - IUMSP - Centre Universitaire de Médecine Générale et Santé Publique Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof Aurélien Thomas - Department of Genetic and Laboratory Medicine, Geneva University Hospitals Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof Serge Rudaz - School of Pharmaceutical Sciences Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Waters Event, Forum Clinique, Maison de l’amerique Latine Talk given at a conference Biomarqueurs d’insufisance renale chronique: une approche metabolomique, 15.01.2020 Paris, France Ponte Belén;
Swiss Society of Nephrology Interlaken Poster Effect of ageing on the decline of renal function overt time: a cohort population-based study. 05.12.2019 Interlaken, Switzerland Ponte Belén;
Swiss Society of Nephrology Interlaken 2019 Poster Metabolomic study can predict long term renal function 05.12.2019 Interlaken, Switzerland Ponte Belén;
Swiss Society of Nephrology Interlaken 2019 Poster Longitudinal metabolomic analysis for the evaluation of kidney transplantation. 05.12.2019 Interlaken, Switzerland Ponte Belén;
Journée de formation, Laboratoire et medicine, SILAMED Talk given at a conference Metabolomique et biomarqueurs d’insuffisance rénale: un nouvel Eldorado? 16.11.2019 Lausanne, Switzerland Ponte Belén;
3rd Int. Symposium on Advances in Pharmaceutical Analysis (APA 2019) Talk given at a conference Metabolomic coverage and data analysis for Chronic Kidney Disease (CKD). 27.10.2019 Xi’an, China Ponte Belén;
Scientific Lecture, Institute of Pharmaceutical Analysis, Junan University, Talk given at a conference Improving the metabolomic coverage with separation techniques hyphenated to MS, the case of Chronic Kidney Disease (CKD) 22.10.2019 Guanzhou, China Ponte Belén;
30th International Symposium on Pharmaceutical and Biomedical Analysis (PBA 2019) Talk given at a conference 5. Current challenges in metabolomics: from analytical coverage to strategies and tools for data integration in Chronic Kidney Disease 15.09.2019 Tel-Aviv, Israel Ponte Belén;
Colloque scientifique du Service de Néphrologie des Hôpitaux Universitaires de Genève Individual talk Métabolomique : principes et applications dans l’IRC. 07.06.2019 Genève, Switzerland Ponte Belén;


Associated projects

Number Title Start Funding scheme
122661 Cardiovascular diseases and psychiatric disorders in the general population: a prospective follow-up study 01.01.2009 Cohort Studies Large
164095 NMR 600MHz for metabolomics and biomarker identification for life sciences, chemical biology and medical projects at the University of Geneva 01.01.2016 R'EQUIP
140331 Blood pressure and renal function genetics 01.04.2012 SPUM
148401 Cardiovascular diseases and psychiatric disorders in the general population: a prospective follow-up study 01.04.2014 Cohort Studies Large
171352 Age-related renal function decline: a comprehensive study using metabolomic analysis 01.05.2017 Marie Heim-Voegtlin grants
139468 Cardiovascular diseases and psychiatric disorders in the general population: a prospective follow-up study 01.04.2012 Cohort Studies Large

Abstract

Par le biais d'une étude de différentes populations, nous essayons de comprendre les mécanismes de la baisse de fonction liée à l'âge. Des profiles métabolomiques différents ont été mis en évidence selon le degré d'atteinte rénale. Certains métabolites semblent également prédire la détérioration de la fonction rénale au cours du temps. Le but du projet actuel est de comprendre les voies biologiques pouvant mener à l'identification de nouveaux marqueurs d'atteinte rénale. Currently, renal function (RF) is estimated by equations, which integrate serum creatinine to calculate a glomerular filtration rate (eGFR). An eGFR<60ml/min is considered as Chronic Kidney Disease (CKD) independently of the age or the presence of any associated complications. When this eGFR threshold is used, almost half of the adults older than 70 are classified as having “kidney disease”. We have previously confirmed the occurrence of a decline in eGFR over 10 years among 2/3 of the general population. We also have found some factors accelerating renal funcion decline (RFD), such as sodium intake, and observed that the decline was particularly steeper in participants with hypertension older than 65 years. The question remains whether all of them have real RFD or CKD, and its associated complications, or whether it is just natural kidney ageing. Therefore, we performed a metabolomic study through different platforms to identify comprehensive markers associated with eGFR. By using different statistical analyses, we identified several metabolites in blood and urine which could predict eGFR modifications. Metabolites profile was also modified when comparing different stages of CKD to controls. Some metabolites increased with CKD (e.g acetyl-L-méthionine) while other decreased (e.g L-tryptophan). Dialysis also affected metabolomic profile. Whether metabolomic analysis will help in understanding and predicting age-related RF decline or CKD incidence still needs to be determined. Also, future analyses and measures should focus on trying to understand pathways through metabolites identification in different study populations. Thus this follow-up project aim is to extend and better characterize the recent findings.
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