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Determinants and prognostic value of renal tissue oxygenation in patients with renal diseases and/or hypertension

English title Determinants and prognostic value of renal tissue oxygenation in patients with renal diseases and/or hypertension
Applicant Burnier Michel
Number 149309
Funding scheme Project funding (Div. I-III)
Research institution Division de Néphrologie et d'Hypertension CHUV
Institution of higher education University of Lausanne - LA
Main discipline Clinical Pathophysiology
Start/End 01.11.2013 - 31.10.2016
Approved amount 520'000.00
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Keywords (4)

Diabetes; Hypertension; Chronic kidney disease; Tissue oxygenation

Lay Summary (French)

Lead
Dans une première partie de notre projet du SNF nommée LauBOLD1 , nous avons établi une cohorte de patients avec maladies rénales, hypertension et des contrôles sains qui contient plus de 200 patients et sujets contrôles et également 40 enfants. Chez ces sujets, nous n'avons pas trouvé de réduction majeure de l'oxygénation rénale au contraire de ce qui a été rapporté chez l'animal.
Lay summary

Déterminants et valeur pronostique de l'oxygénation du tissu rénal dans les maladies rénales et l'hypertension artérielle

Le but de projet est de clarifier encore mieux les déterminants de l'oxygénation rénale chez l'homme en particulier le rôle de la glycémie et de l'hyperfiltration liée à la consommmation de protéines. D'autre part, nous allons poursuivre le suivi à 5 ans de nos patients avec de nouvellles IRM dans le cadre de la phase deux du protocole (LauBold-2) pour étudier le lien entre l'oxygénation et la progression de la maladie rénale et en particulier la fibrose rénale. Pour cela, nous allons aussi développer de nouveaux outils pour quantifier la fibrose rénale et mettre en relation les données obtenues avec la qualité de l'oxygénation tissulaire.
Ces études seront particulièrement intéressantes pour mieux comprendre le rôle de l'oxygénation tissulaire dans la progression des maladies rénales. A l'heure où des médicaments sont développés pour augmenter les apports d'oxygène au niveau du rein, nos observations pourraient s'avérer importantes pour les patients et notre compréhension de la maldie rénale chronique.

Direct link to Lay Summary Last update: 08.10.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Renal tissue oxygenation in children with chronic kidney disease due to vesico-ureteral reflux.
Chehade Hassib, Milani Bastien, Ansaloni Annalisa, Anex Christiane, Bassi Isabelle, Piskunowicz Maceij, Stuber Mathias, Cachat Francois, Burnier Michel, Pruijm Menno (2016), Renal tissue oxygenation in children with chronic kidney disease due to vesico-ureteral reflux., in Pediatric Nephrology, 31(11), 2103-2111.
A new technique with high reproducibility to estimate renal oxygenation using BOLD-MRI in chronic kidney disease
Maciej Piskunowicz (2015), A new technique with high reproducibility to estimate renal oxygenation using BOLD-MRI in chronic kidney disease, in Magnetic Res Imaging , 33(3), 253-261.
Comparative Effect of a Renin Inhibitor and a Thiazide Diuretic on Renal Tissue Oxygenation in Hypertensive Patients.
Vakilzadeh N et al (2015), Comparative Effect of a Renin Inhibitor and a Thiazide Diuretic on Renal Tissue Oxygenation in Hypertensive Patients., in Kidney Blood Press Res, 40(5), 542-554.
Determinants of Renal Tissue Oxygenation as Measured with BOLD-MRI in Chronic Kidney Disease and Hypertension in Humans
Pruijm M. et al (2014), Determinants of Renal Tissue Oxygenation as Measured with BOLD-MRI in Chronic Kidney Disease and Hypertension in Humans, in PLOS One, 9(4): e95895, 1-10.
Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers.
Pruijm M et al (2013), Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers., in Clinical Nephrology, 80(3), 211-217.
Reduction of cortical oxygenation in chronic kidney disease: evidence obtained with a new analysis method of blood oxygenation level-dependent magnetic resonance imaging.
Milani Bastien, Ansaloni Annalisa, Sousa-Guimaraes S, Vakilzadeh Nima, Piskunowicz Maceij, Vogt Bruno, Stuber Mathias, Burnier Michel, Pruijm Menno, Reduction of cortical oxygenation in chronic kidney disease: evidence obtained with a new analysis method of blood oxygenation level-dependent magnetic resonance imaging., in Nephrology Dialysis and Transplantation.

Collaboration

Group / person Country
Types of collaboration
Medical University of Gdansk Poland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Service de Néphrologie et Hypertension, Hôpital Universitaire de Bern, Inselspital Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
26th European Society of Hypertension and cardiovascular protection Individual talk Reduction of renal tissue oxygenation in CKD: evidence obtained with a BOLD-MRI and a new analytic technique 13.06.2016 Paris, France Pruijm Menno;
26th European meeting on Hypertension and cardiovascular protection Individual talk Renal oxygenation using BOLD-MRI 12.06.2016 Paris, France Pruijm Menno;
European Society of Hypertension, Paris, 2016 Talk given at a conference Effect of acute hyperglycemia on renal tissue oxygenation as measured with BOLD-MRI in overweight individuals. 12.06.2016 Paris, France Pruijm Menno; Burnier Michel;
53rd ERA/EDTA Congress Talk given at a conference BOLD-MRI: a key measure to diagnose ischemic nephropathy 22.05.2016 Vienna, Austria Pruijm Menno;
53rd ERA/EDTA Congress Talk given at a conference BOLD-MRI: a key measure to diagnose ischemic nephropathy. Reduction of renal tissue oxygenation in CKD: evidence obtained with BOLD-MRI. 22.05.2016 Vienna, Austria Burnier Michel; Pruijm Menno;
2nd European forum on Hypertension Talk given at a conference Progression in the diagnosis of arterial hypertension: the kidney. 13.05.2016 Gdansk, Poland Pruijm Menno;
46th SGN-SSN congress (Swiss Society of Nephrology) Poster Effect of acute hyperglycemia on renal tissue oxygenation as measured with BOLD-MRI in overweight individuals and persons with impaired glucose tolerance 03.12.2015 Basel, Switzerland Milani Bastien; Pruijm Menno; Burnier Michel;
Joint Lecture of general radiology and AMSM's series Talk given at a conference Functional MRI to predict decline of kidney function: too BOLD to be true? 15.10.2015 Bern, Switzerland Pruijm Menno;
Third annual retreat of cardiovascular MRI centers Talk given at a conference Filtering the important things with the kidneys 11.09.2015 Annecy, France Pruijm Menno;
Annual Meeting of the European Society of Hypertension Talk given at a conference Determination of renal oxygenation by BOLD-MRI 13.06.2015 Milan, Italy Pruijm Menno; Burnier Michel;
European Society of Hypertension Talk given at a conference Comparative effects of aliskiren and hydrochlorthiazide on renal tissue oxygenation in patients with arterial hypertension: a BOLD MRI study. 13.06.2015 Milan, Italy Pruijm Menno; Burnier Michel;
ISMRM, Toronto, Canada. Talk given at a conference Radial R2* distribution: a new method to analyze BOLD-MRI of kidneys. 01.06.2015 Toronto, Canada Milani Bastien;
45th SGN-SSN congress (Swiss Society of Nephrology) Poster Renal tissue oxygenation as measured with BOLD-MRI in children with vesico-ureteral reflux or a solitary kidney in comparison with healthy controls. 05.12.2014 Interlaken, Switzerland Pruijm Menno;
Gesellschaft für Nephrologie Congress, Berlin, Germany Individual talk BOLD-MRI: new aspects of functional renal MRI. 08.09.2014 Berlin, Germany Vogt Bruno;


Associated projects

Number Title Start Funding scheme
169191 Gender differences in renal disease progression: an analysis of potential mechanisms using modern radiological techniques. 01.10.2016 Project funding (Div. I-III)
150828 Development of Advanced Translational High-Field MRI 12.05.2014 R'EQUIP
132913 Prognostic value of renal tissue oxygenation on renal disease progression in patients with hypertension and renal diseases 01.10.2010 Project funding (Div. I-III)

Abstract

Animal studies suggest that renal tissue hypoxia plays an important role in the development of acute and chronic kidney diseases (CKD) due to its role in inducing acute tubular necrosis and interstitial fibrosis. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), detecting local tissular deoxyhemoglobin concentrations which correspond to R2* levels, is the only available technique to assess renal tissue oxygenation non-invasively in humans. Acute alterations in cortical and medullary R2* levels have been observed in acute disease states and in response to changes in dietary sodium intake or the administration of drugs such as furosemide. However, the long-term impact of renal oxygenation on the progression of renal diseases remains unknown. The purpose of our SNF project was therefore to assess the prognostic value of renal tissue oxygenation in patients with hypertension and/or CKD. To this purpose, we have started to establish a cohort of CKD and hypertensive patients which now includes about 200 patients (LauBOLD-1) in whom renal oxygenation was measured at baseline and will be measured during follow-up years to evaluate the relationship between renal disease progression and renal tissue oxygenation. Interestingly, in contrast to animal studies, we have so far not found any marked reduction in tissue renal oxygenation in CKD patients when compared to normotensive or hypertensive subjects. This finding suggests that renal tissue oxygenation is well regulated and it raises the question whether chronic renal tissue hypoxia truly exists in humans and does contribute to renal disease progression. Thus, hypoxia-induced fibrosis may not be a vicious circle that further worsens oxygenation, but merely a way to maintain renal oxygenation by adapting oxygen consumption to the demand. Alternatively, actual BOLD-MRI techniques might not be sensitive enough to detect small local changes in oxygenation and there is a need to improve assessment of renal tissue oxygenation in humans, by combining our actual approach with other complementary MR techniques. Clarification of these issues is of scientific and clinical importance for improving the understanding of the pathophysiology of chronic kidney diseases. Our observations may be of particular interest in the light of the actual development of drugs interfering with renal oxygen-sensing mechanisms and interstitial fibrosis. The aim of this project is therefore to increase the understanding of renal tissue oxygenation homeostasis in humans, and to further establish its role in CKD progression. In this context, the main aims of our project are:1/ To assess the long-term consequences of baseline renal oxygenation as estimated with BOLD-MRI on renal function decline in CKD patients and hypertensive patients.2/ To assess the relative contribution of renal microcirculation, interstitial fibrosis and sodium handling to renal tissue oxygenation, using new MRI techniques and updated methods of analysis of MRI data.3/ To correlate histological markers of renal tissue hypoxia on renal biopsies and nephrectomized kidneys with renal R2* levels and apparent diffusion coefficients as assessed with BOLD-MRI and diffusion MRI.4/ To investigate the impact of two important determinants of renal disease progression i.e. glycemia and protein intake, on renal tissue oxygenation.
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