Diabetes; Hypertension; Chronic kidney disease; Tissue oxygenation
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.
Maciej Piskunowicz (2015), A new technique with high reproducibility to estimate renal oxygenation using BOLD-MRI in chronic kidney disease, in Magnetic Res Imaging
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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
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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.
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.
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
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.