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Gender differences in renal disease progression: an analysis of potential mechanisms using modern radiological techniques.

English title Gender differences in renal disease progression: an analysis of potential mechanisms using modern radiological techniques.
Applicant Pruijm Menno
Number 169191
Funding scheme Project funding (Div. I-III)
Research institution Service de Médecine Interne Département de Médecine CHUV
Institution of higher education University of Lausanne - LA
Main discipline Clinical Pathophysiology
Start/End 01.10.2016 - 31.10.2019
Approved amount 474'000.00
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Keywords (6)

Gender; Chronic kidney disease; Acute kidney injury; Contrast-enhanced Ultrasound; Renal sodium handling; MRI

Lay Summary (French)

Lead
L'insuffisance rénale chronique (IRC) touche environ 10% de la population adulte en Suisse. Les personnes avec IRC ont une morbidité et mortalité cardiovasculaire élevée. En plus, en cas de déclin progressif de leur fonction rénale, des thérapies lourdes et couteuses comme la dialyse, ou la transplantation sont nécessaires. Malgré des décennies de recherche, les mécanismes impliqués dans le développement et la progression de l'IRC restent peu clairs, et il y a un manque de thérapies préventives. Les femmes sont relativement protégées contre l'IRC, mais ce sujet a été peu étudié. Le but de ce projet est donc d'investiguer quels mécanismes sont responsables de la protection des reins chez les femmes, en utilisant des techniques modernes d'imagerie.
Lay summary

Nous avons récemment démontré avec le BOLD-IRM (blood oxygenation level-dependent MRI) que l'oxygénation rénale est plus élevée chez les femmes que chez les hommes, mais la signification de cette découverte est incertaine. Dans ce projet nommé GenderBOLD, des femmes en bonne santé ou avec IRC seront examinées pendant différentes phases de leur cycle, et différents régimes alimentaires (riche ou pauvre en sel, avant et après L-arginine). A chacune des visites, une IRM fonctionnelle (BOLD, Na23 et diffusion) sera effectuée, ainsi qu'un ultrason à microbulles. Ceci nous permettra d'établir le rôle des hormones sexuelles dans la perfusion et oxygénation rénale. L'ultrason à microbulles avant et après l'administration de L-arginine chez une sous-groupe (hommes et femmes avec insuffisance rénale aigue aux soins intensifs) représente possiblement une nouvelle façon de mieux prédire le devenir des reins dans une situation de stress extrême. Finalement, en collaboration avec le département de médecine légale, nous étudierons les éventuelles différences anatomiques et histologiques rénales entre les hommeset les femmes.

Nous espérons, grâce aux connaissances ainsi acquises, d'ouvrir le chemin vers de nouvelles stratégies préventives et thérapeutiques pour les hommes et les femmes souffrant d'IRC.


 
Direct link to Lay Summary Last update: 11.10.2016

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Consensus-based technical recommendations for clinical translation of renal BOLD MRI
Bane Octavia, Mendichovszky Iosif A., Milani Bastien, Dekkers Ilona A., Deux Jean-Francois, Eckerbom Per, Grenier Nicolas, Hall Michael E., Inoue Tsutomu, Laustsen Christoffer, Lerman Lilach O., Liu Chunlei, Morrell Glen, Pedersen Michael, Pruijm Menno, Sadowski Elizabeth A., Seeliger Erdmann, Sharma Kanishka, Thoeny Harriet, Vermathen Peter, Wang Zhen J., Serafin Zbigniew, Zhang Jeff L., Francis Susan T., et al. (2019), Consensus-based technical recommendations for clinical translation of renal BOLD MRI, in Magnetic Resonance Materials in Physics, Biology and Medicine, 1-10.
Short-term changes in dietary sodium intake influence sweat sodium concentration and muscle sodium content in healthy individuals
Braconnier Philippe, Milani Bastien, Loncle Nicolas, Lourenco Joao M., Brito Wendy, Delacoste Jean, Maillard Marc, Stuber Matthias, Burnier Michel, Pruijm Menno (2019), Short-term changes in dietary sodium intake influence sweat sodium concentration and muscle sodium content in healthy individuals, in Journal of Hypertension, 1-1.
Exploring a new method for quantitative sodium MRI in the human upper leg with a surface coil and symmetrically arranged reference phantoms
Milani Bastien, Delacoste Jean, Burnier Michel, Pruijm Menno (2019), Exploring a new method for quantitative sodium MRI in the human upper leg with a surface coil and symmetrically arranged reference phantoms, in Quantitative Imaging in Medicine and Surgery, 9(6), 985-999.
Renal handling of zinc in chronic kidney disease patients and the role of circulating zinc levels in renal function decline
Damianaki Katerina, Lourenco Joao Miguel, Braconnier Philippe, Ghobril Jean-Pierre, Devuyst Olivier, Burnier Michel, Lenglet Sebastien, Augsburger Marc, Thomas Aurelien, Pruijm Menno (2019), Renal handling of zinc in chronic kidney disease patients and the role of circulating zinc levels in renal function decline, in Nephrology Dialysis Transplantation, 21(April), 1-8.
Acute hyperglycemia increases renal tissue oxygenation as measured by BOLD-MRI in healthy overweight volunteers
Vakilzadeh Nima, Zanchi Anne, Milani Bastien, Ledoux Jean-Baptiste, Braconnier Philippe, Burnier Michel, Pruijm Menno (2019), Acute hyperglycemia increases renal tissue oxygenation as measured by BOLD-MRI in healthy overweight volunteers, in Diabetes Research and Clinical Practice, 150, 138-143.
The skin as third kidney
Wurzner-GhajarzadehArlene, BraconnierPhilippe, BurnierMichel, Pruijm Menno (2019), The skin as third kidney, in Revue Medicale Suisse, 15(639), 418-421.
Hypoxia in Kidney Disease
Maarten Koeners, Fredrik Palm (2018), Hypoxia in Kidney Disease, Frontiers Media SA, Frontiers in Physiology.
Functional magnetic resonance imaging of the kidneys: where do we stand? The perspective of the European COST Action PARENCHIMA
Caroli Anna, Pruijm Menno, Burnier Michel, Selby Nicholas M (2018), Functional magnetic resonance imaging of the kidneys: where do we stand? The perspective of the European COST Action PARENCHIMA, in Nephrology Dialysis Transplantation, 33(suppl_2), ii1-ii3.
Renal blood oxygenation level-dependent magnetic resonance imaging to measure renal tissue oxygenation: a statement paper and systematic review
Pruijm Menno, Mendichovszky Iosif A, Liss Per, Van der Niepen Patricia, Textor Stephen C, Lerman Lilach O, Krediet C T Paul, Caroli Anna, Burnier Michel, Prasad Pottumarthi Vara (2018), Renal blood oxygenation level-dependent magnetic resonance imaging to measure renal tissue oxygenation: a statement paper and systematic review, in Nephrology Dialysis Transplantation, 33(suppl_2), ii22-ii28.
Reduced cortical oxygenation predicts a progressive decline of renal function in patients with chronic kidney disease
Pruijm Menno, Milani Bastien, Pivin Edward, Podhajska Agata, Vogt Bruno, Stuber Matthias, Burnier Michel (2018), Reduced cortical oxygenation predicts a progressive decline of renal function in patients with chronic kidney disease, in Kidney International, 93(4), 932-940.
Serum calcification propensity is associated with renal tissue oxygenation and resistive index in patients with arterial hypertension or chronic kidney disease.
Pruijm Menno, Lu Yimin, Megdiche Fatma, Piskunowicz Maciej, Milani Bastien, Stuber Matthias, Bachtler Matthias, Vogt Bruno, Burnier Michel, Pasch Andreas (2017), Serum calcification propensity is associated with renal tissue oxygenation and resistive index in patients with arterial hypertension or chronic kidney disease., in Journal of hypertension, 35(10), 2044-2052.
[Gender differences in chronic kidney diseases : myth or reality ?]
Mehier Patricia, Burnier Michel, Pruijm Menno (2017), [Gender differences in chronic kidney diseases : myth or reality ?], in Revue medicale suisse, 13(551), 473-476.
Blood Oxygenation Level-Dependent MRI to Assess Renal Oxygenation in Renal Diseases: Progresses and Challenges.
Pruijm Menno, Milani Bastien, Burnier Michel (2016), Blood Oxygenation Level-Dependent MRI to Assess Renal Oxygenation in Renal Diseases: Progresses and Challenges., in Frontiers in physiology, 7, 667-667.
Premature Destruction of Microbubbles during Voiding Urosonography in Children and Possible Underlying Mechanisms: Post Hoc Analysis from the Prospective Study
Piskunowicz Maciej, Swieton Dominik, Rybczynska Dorota, Szarmach Arkadiusz, Szurowska Edyta, Pruijm Menno (2016), Premature Destruction of Microbubbles during Voiding Urosonography in Children and Possible Underlying Mechanisms: Post Hoc Analysis from the Prospective Study, in BIOMED RESEARCH INTERNATIONAL, 1-7.
Renal tissue oxygenation in children with chronic kidney disease due to vesicoureteral reflux
Chehade Hassib, Milani Bastien, Ansaloni Annalisa, Anex Christiane, Bassi Isabelle, Piskunowicz Maciej, Stuber Matthias, Cachat Francois, Burnier Michel, Pruijm Menno (2016), Renal tissue oxygenation in children with chronic kidney disease due to vesicoureteral reflux, in PEDIATRIC NEPHROLOGY, 31(11), 2103-2111.

Collaboration

Group / person Country
Types of collaboration
EPFL, Esmeralda Megally Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Industry/business/other use-inspired collaboration
Prof. Aurélien Thomas, University of Lausanne, Unit of Toxicology, CURML Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
COST action PARENCHIMA (www.renalmri.org) Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
University Hospital of Zürich, Prof. Olivier Devuyst Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Swiss Society of Nephrology congress Poster Contrast-enhanced and Doppler ultrasound to assess renal microcirculation in healthy subjects and patients with chronic kidney disease before and after vasodilatation with nitroglycerin 05.12.2019 Interlaken, Switzerland Brito Wendy; Pruijm Menno; Garessus Jonas;
3rd International Symposium on functional renal MRI Talk given at a conference Renal BOLD-MRI for non-experts 15.10.2019 Nottingham, Great Britain and Northern Ireland Brito Wendy; Pruijm Menno;
European Society of Hypertension congress Talk given at a conference Is relative renal kidney mass larger in women? 22.06.2019 Milan, Italy Garessus Jonas; Pruijm Menno;
Cutting Edge in Nephrology Talk given at a conference How can we apply the latest technologies in MR technology in detecting renal hypoxia? 21.03.2019 Copenhague, Denmark Pruijm Menno;
55th ERA-EDTA congress Talk given at a conference SODIUM AND CHLORIDE CONCENTRATION OF SWEAT CORRELATE WITH DIETARY SALT INTAKE IN HEALTHY SUBJECTS 25.05.2018 Copenhague, Denmark Stuber Matthias; Pruijm Menno; Milani Bastien; Brito Wendy; Loncle Nicolas;
European Society of Hypertension congress Talk given at a conference Reduced renal tissue oxygenation with ageing in men, but not in women 18.06.2017 Milan, Italy Stuber Matthias; Pruijm Menno; Milani Bastien;
ERA-EDTA congress Talk given at a conference Predicting decline of eGFR with BOLD-MRI 05.06.2017 Madrid, Spain Pruijm Menno; Stuber Matthias; Milani Bastien;


Self-organised

Title Date Place
35me Réunion Romand de Néphorlogie. L'imagerie et le rein anno 2019 11.04.2019 Lausanne, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: radio, television La peau comme troisième rein RTL Western Switzerland 2019
Media relations: radio, television Une nouvelle maladie due au changement climatique RTL Western Switzerland 2019

Associated projects

Number Title Start Funding scheme
149309 Determinants and prognostic value of renal tissue oxygenation in patients with renal diseases and/or hypertension 01.11.2013 Project funding (Div. I-III)
173129 A Paradigm Shift in Magnetic Resonance Imaging of the Heart: 5D Imaging - Sample Now and Ask Questions Later 01.06.2017 Project funding (Div. I-III)

Abstract

Chronic kidney disease (CKD) is a fast growing global health problem with an estimated prevalence in Switzerland of ~10%. Despite important research efforts, the available preventive and therapeutic strategies are not very successful in halting the CKD epidemic. Of interest, women are less prone to the development of CKD, suffer less often from hypertension, and progress less rapidly to end stage renal disease. This protection seems lost when entering menopause. Why women are protected remains so far incompletely understood. In experimental models, chronic renal tissue hypoxia is a common and final pathway of CKD, irrespective of its cause. Using blood oxygenation level-dependent MRI (BOLD-MRI), we have recently demonstrated that CKD patients have indeed lower cortical oxygenation than controls. Of importance for this project, in both groups cortical oxygenation was higher in women than men. Renal tissue oxygenation depends of anatomical (renal size, renal arteries, glomeruli number, degree of fibrosis), dietary (fluid and sodium intake), and functional parameters (renal blood flow, renal sodium handling, glomerular filtration rate, tubular active transport). The impact of sex hormones on renal oxygenation in humans is, so far, unknown. We hypothesize that the higher cortical oxygenation in women is due to sex differences in relative cortical perfusion, renal and skin sodium handling, different responses to external factors, and differences in renal anatomy (size) and histology (number of glomeruli). We also hypothesize that fluctuations in renal oxygenation take place during the menstrual cycle, menopause and under the influence of oral anticonceptives. New radiological and histological techniques offer unique opportunities to study the above mentioned factors and will be used in this project, yet some techniques have to be further developed, or used in new ways. In this context, the main aims of this project are:1/ To assess the influence of menstrual cycle and menopause on renal oxygenation, hemodynamics and sodium handling using BOLD MRI, diffusion weighted MRI, Na23 MRI and CEUS.2/ To assess whether sex differences exist in renal perfusion in response to external stimuli (L-arginine) in normal and stressful (acute kidney injury) conditions using contrast-enhanced ultrasound (CEUS).3/ To develop a new analysis technique of CEUS to acquire detailed, layer by layer, information on renal perfusion.4/ To assess whether renal structural and histological differences exist between men and women using autopsy data and histological techniques that will be further developed in the light of this project(automatic counting of glomeruli)
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