Determinants of renal tissue oxygenation as measured with BOLD-MRI in chronic kidney disease and hypertension in humans.

Menno Pruijm,Isabelle Bassi,Maciej Piskunowicz,Matthias Stuber,Carole Zweiacker,Marie-Eve Muller,Michel Burnier,Bruno Vogt,Lucie Hofmann,Jaap A Joles

doi:10.1371/journal.pone.0095895

Abstract

Experimentally renal tissue hypoxia appears to play an important role in the pathogenesis of chronic kidney disease (CKD) and arterial hypertension (AHT). In this study we measured renal tissue oxygenation and its determinants in humans using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) under standardized hydration conditions. Four coronal slices were selected, and a multi gradient echo sequence was used to acquire T2* weighted images. The mean cortical and medullary R2* values ( = 1/T2*) were calculated before and after administration of IV furosemide, a low R2* indicating a high tissue oxygenation. We studied 195 subjects (95 CKD, 58 treated AHT, and 42 healthy controls). Mean cortical R2 and medullary R2* were not significantly different between the groups at baseline. In stimulated conditions (furosemide injection), the decrease in R2* was significantly blunted in patients with CKD and AHT. In multivariate linear regression analyses, neither cortical nor medullary R2* were associated with eGFR or blood pressure, but cortical R2* correlated positively with male gender, blood glucose and uric acid levels. In conclusion, our data show that kidney oxygenation is tightly regulated in CKD and hypertensive patients at rest. However, the metabolic response to acute changes in sodium transport is altered in CKD and in AHT, despite preserved renal function in the latter group. This suggests the presence of early renal metabolic alterations in hypertension. The correlations between cortical R2* values, male gender, glycemia and uric acid levels suggest that these factors interfere with the regulation of renal tissue oxygenation.

Highlights

Numerous experimental studies have suggested that disturbed oxygenation plays a role in the development and progression of kidney disease including hypertensive nephropathy[1,2,3].using micro-electrodes for direct pO2 measurements, low cortical O2 levels have been found in spontaneous hypertensive rats and in rats with streptozotocine-induced diabetes or in the subtotal nephrectomy model [4,5].Until recently, human data were largely lacking mainly due to the lack of non-invasive methods to estimate renal tissue oxygenation
The main findings of this study are that: 1) mean cortical and medullary R2* values as a proxy for renal tissue oxygenation are similar in hypertensive patients, chronic kidney disease (CKD) patients and healthy controls; the distribution of cortical R2* values differs markedly between groups, 2) the medullary R2* response to furosemide is blunted in hypertensive patients and markedly reduced in CKD patients, 3) baseline renal tissue oxygenation appears to be remarkably stable over different degrees of kidney dysfunction, independently of the cause of kidney disease and 4) cortical R2* levels are positively associated with male gender, glycemia and uric acid levels
Our data suggest that renal tissue oxygenation at rest is comparable in controls, treated hypertensives and CKD patients

Summary

Introduction

Human data were largely lacking mainly due to the lack of non-invasive methods to estimate renal tissue oxygenation. Blood oxygenation leveldependent magnetic resonance imaging (BOLD-MRI) has become a powerful tool to estimate renal tissue oxygenation non-invasively in humans. Using post-processing programs, several circles - called regions of interest (ROI’s) - are placed manually per slice in the cortex and in the medulla. This allows the assessment of the average cortical and medullary R2* value, per kidney or for both kidneys together, without the need to administer contrast product [7]

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