Project

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

Applicant Ponte Belén
Number 171352
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 01.05.2017 - 30.04.2019
Approved amount 185'810.00
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All Disciplines (2)

Discipline
Internal Medicine
Methods of Epidemiology and Preventive Medicine

Keywords (5)

Ageing; Biomarkers; Chronic kidney Disease; Metabolomic; Renal Function

Lay Summary (French)

Lead
L’insuffisance rénale chronique (IRC), qui est associée à une mortalité et morbitidé importante, est actuellement en pleine croissance sur le plan épidémiologique. L’IRC est définie notamment par un taux de filtration glomérulaire (TFG) <60ml/min/1.73m2, souvent estimé à partir d’équations. Hors, avec l‘implémentation de cette définition, la prévalence de l’IRC chez la personne âgée a fortement augmenté. Il n’est pas encore clair si le déclin du TFG chez la personne âgée est associé aux complications de l’IRC. D’autres marqueurs de la fonction rénale pourraient permettre une meilleure compréhension des mécanismes de la baisse de fonction rénale liée à l’âge.
Lay summary

L’objectif principal du projet est de trouver des marqueurs plus spécifiques de la fonction rénale que l’estimation du TFG par les équations, en utilisant la métabolomique dans différentes cohortes. Cette méthode permet l’analyse et la découverte de métabolites dans le sang et l’urine. Nous espérons donc identifier parmi les métabolites qui seront analysés certains marqueurs associés à la fonction rénale. Ceci devrait ensuite permettre de déterminer si la baisse de fonction rénale liée à l’âge peut être prédite par certains métabolites. Les facteurs généraux de la baisse de fonction rénale liée à l’âge seront également analysés dans des cohortes longitudinales. Il est important de comprendre les modifications de la fonction rénale liée à l’âge et les mécanismes qui y sont liés. Une meilleure compréhension permettrait en effet de savoir quand s’inquiéter d’une baisse de fonction rénale chez le sujet âgé. L’identification de métabolites devrait permettre d’identifier différents profiles selon la détérioration de la fonction rénale et peut être mettre en évidence de nouveaux mécanismes.

 

Direct link to Lay Summary Last update: 23.01.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
Gaining Insights Into Metabolic Networks Using Chemometrics and Bioinformatics: Chronic Kidney Disease as a Clinical Model
Boccard Julien, Schvartz Domitille, Codesido Santiago, Hanafi Mohamed, Gagnebin Yoric, Ponte Belén, Jourdan Fabien, Rudaz Serge (2021), Gaining Insights Into Metabolic Networks Using Chemometrics and Bioinformatics: Chronic Kidney Disease as a Clinical Model, in Frontiers in Molecular Biosciences, 8, 13.
Exploring blood alterations in chronic kidney disease and haemodialysis using metabolomics
Gagnebin Yoric, Jaques David A., Rudaz Serge, de Seigneux Sophie, Boccard Julien, Ponte Belén (2020), Exploring blood alterations in chronic kidney disease and haemodialysis using metabolomics, in Scientific Reports, 10(1), 19502-19502.
Sodium Intake Is Associated With Renal Resistive Index in an Adult Population-Based Study
Jaques David A., Pruijm Menno, Ackermann Daniel, Vogt Bruno, Guessous Idris, Burnier Michel, Pechere-Bertschi Antoinette, Bochud Murielle, Ponte Belen (2020), Sodium Intake Is Associated With Renal Resistive Index in an Adult Population-Based Study, in Hypertension, 76(6), 1898-1905.
Circulating Uromodulin and Risk of Cardiovascular Events and Kidney Failure
Ponte Belen, Devuyst Olivier (2020), Circulating Uromodulin and Risk of Cardiovascular Events and Kidney Failure, in Clinical Journal of the American Society of Nephrology, 15(5), 589-591.
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 (2020), Parathyroid Hormone and Plasma Phosphate Are Predictors of Soluble α-Klotho Levels in Adults of European Descent, in The Journal of Clinical Endocrinology & Metabolism, 105(4), e1135-e1143.
Dialysis initiation improves calcification propensity
Ponte Belen, Pruijm Menno, Pasch Andreas, Dufey-Teso Anne, Martin Pierre-Yves, de Seigneux Sophie (2020), Dialysis initiation improves calcification propensity, in Nephrology Dialysis Transplantation, 35(3), 495-502.
Combining the advantages of multilevel and orthogonal partial least squares data analysis for longitudinal metabolomics: Application to kidney transplantation
Gagnebin Yoric, Pezzatti Julian, Lescuyer Pierre, Boccard Julien, Ponte Belen, Rudaz Serge (2020), Combining the advantages of multilevel and orthogonal partial least squares data analysis for longitudinal metabolomics: Application to kidney transplantation, in Analytica Chimica Acta, 1099, 26-38.
Toward a better understanding of chronic kidney disease with complementary chromatographic methods hyphenated with mass spectrometry for improved polar metabolome coverage
Gagnebin Yoric, Pezzatti Julian, Lescuyer Pierre, Boccard Julien, Ponte* Belén, Rudaz* Serge (2019), Toward a better understanding of chronic kidney disease with complementary chromatographic methods hyphenated with mass spectrometry for improved polar metabolome coverage, in Journal of Chromatography B, 1116, 9-18.
Estimated 24-h urinary sodium and sodium-to-potassium ratio are predictors of kidney function decline in a population-based study
Deriaz Denis, Guessous Idris, Vollenweider Peter, Devuyst Olivier, Burnier Michel, Bochud Murielle, Ponte Belen (2019), Estimated 24-h urinary sodium and sodium-to-potassium ratio are predictors of kidney function decline in a population-based study, in Journal of Hypertension, 1-1.
Reference intervals for the urinary steroid metabolome: The impact of sex, age, day and night time on human adult steroidogenesis
Ackermann Daniel, Groessl Michael, Pruijm Menno, Ponte Belen, Escher Geneviève, d’Uscio Claudia H., Guessous Idris, Ehret Georg, Pechère-Bertschi Antoinette, Martin Pierre-Yves, Burnier Michel, Dick Bernhard, Vogt Bruno, Bochud Murielle, Rousson Valentin, Dhayat Nasser A. (2019), Reference intervals for the urinary steroid metabolome: The impact of sex, age, day and night time on human adult steroidogenesis, in PLOS ONE, 14(3), e0214549-e0214549.
Metabolomics in chronic kidney disease: Strategies for extended metabolome coverage
Gagnebin Yoric, Julien Boccard, Belén Ponte, Serge Rudaz (2018), Metabolomics in chronic kidney disease: Strategies for extended metabolome coverage, in Journal of Pharmaceutical and Biomedical Analysis, 161, 313-325.

Collaboration

Group / person Country
Types of collaboration
Prof Serge Rudaz - School of Pharmaceutical Sciences Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
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 Aurélien Thomas - Department of Genetic and Laboratory Medicine, Geneva University Hospitals Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
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
- Exchange of personnel
Prof Sven Bergmann - Département of Computonal Biology - University of Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Société Suisse de Néphrologie (SSN) Talk given at a conference Estimated 24h urinary sodium and sodium-to-potassium ratio are predictors of kidney function decline: a 5-year cohort study. 07.12.2018 Interlaken, Switzerland Ponte Belén;
Seminar Series - Centre Facultaire d'Investigation Translationnelle en Biomarqueurs (CITB) Individual talk Towards a better understanding of kidney disease 13.11.2018 Genève, Switzerland Ponte Belén;
32nd Int. Symposium on Chromatography, ISC 2018 Poster IV. Metabolomics in chronic kidney disease: toward a better understanding of disease progression and hemodialysis 23.09.2018 Cannes, France Ponte Belén;
29th International Symposium on Pharmaceutical and Biomedical Analysis Talk given at a conference Metabolomic insights into chronic kidney disease and hemodialysis 09.09.2018 Leuven, Belgium Ponte Belén;
Société Suisse de Médecine Interne Générale (SSMIG) Talk given at a conference Estimated 24h urinary sodium and sodium-to-potassium ratio as predictors of kidney function decline in a population-based study 30.05.2018 Bâle, Switzerland Ponte Belén;
European Dialysis and Transplantation Society (EDTA) Poster 24h urinary sodium and sodium-to-potassium ratio as predictors of renal function decline in a population-based study 24.05.2018 Copenhague, Switzerland Ponte Belén;
European Dialysis and Transplantation Society (EDTA) Talk given at a conference TOWARD A BETTER UNDERSTANDING OF CHRONIC KIDNEY DISEASE USING METABOLOMICS 24.05.2018 Copenhague, Switzerland Ponte Belén;
11e Journées Scientifiques du Réseau Francophone de Métabolomique et Fluxomique (RFMF) Poster III. Multi-platform data integration for improved metabolite coverage: application to chronic kidney disease 23.05.2018 Liège, Belgium Ponte Belén;
Metabomeeting Poster II. Toward a better understanding of chronic kidney disease using multi-platform metabolomics and data fusion 11.12.2017 Birmingham, Great Britain and Northern Ireland Ponte Belén;
Societé Suisse de Néphrologie (SSN) Talk given at a conference TOWARD A BETTER UNDERSTANDING OF CHRONIC KIDNEY DISEASE USING METABOLOMICS 06.12.2017 Fribourg, Switzerland Ponte Belén;
Joined congress of Mass Spectrometry, Metabolomics and Proteomics Analysis Poster Multi-platform metabolomic and data fusion: application to chronic kidney disease 02.10.2017 Marne-la-Vallée, France Ponte Belén;


Self-organised

Title Date Place
3rd Biomarker Day dedicated to ageing 19.10.2018 Hôpitaux Universitaires Genève, Germany

Awards

Title Year
2nd Best Poster Award - 32nd Int. Symposium on Chromatography, ISC 2018 2018

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
139468 Cardiovascular diseases and psychiatric disorders in the general population: a prospective follow-up study 01.04.2012 Cohort Studies Large
148401 Cardiovascular diseases and psychiatric disorders in the general population: a prospective follow-up study 01.04.2014 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
124087 Blood pressure and the kidney: interface between genes and environment 01.04.2009 SPUM
186203 Age-related renal function decline: a comprehensive study using metabolomic analysis 01.05.2019 Marie Heim-Voegtlin grants

Abstract

Chronic kidney disease (CKD) is associated with increased mortality and morbidity. Currently, the estimation of renal function (RF) is estimated by equations, which integrate serum creatinine to calculate a glomerular filtration rate (GFR). A GFR<60ml/min is considered as CKD independently of the age or the presence of any associated complications. However, by using equations, the prevalence of CKD has dramatically increased in the elderly population. Whether the decline in GFR in elderly is really associated with complications associated with CKD is not clear so far. There are some evidences that RF decreases with age as shown by some functional, structural and morphological changes. However, we should find more comprehensive markers of RF which are not restrain to GFR only. The identification of new biomarkers is not only necessary to detect CKD at an early stage or to be more specific about its detection, it is also an approach to find new biological pathways helping understanding disease mechanisms. The availability of mass spectrometers to perform metabolomic analysis in blood, urine or tissue, has led to numerous findings and the discovery of many proteins. However, for some of them, their true function and their relation with the kidney still need to be determined. Whether metabolomic analysis will help understanding and predicting age-related RF decline still needs to be determined. Efforts to understand the age-related changes and mechanisms would help identifying potential targets for early interventions aiming at preventing CKD-related morbidity and mortality. In addition, a better understanding of age-related RF decline would help clarifying whenever such decline should be considered as worrisome. In this project, we aim at using metabolomic analyses to understand the decline of RF associated with ageing and see whether CKD patients exhibit different metabolic profiles that patients without CKD or RF decline.
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