Noninvasive evaluation of renal oxygenation in diabetic nephropathy by BOLD-MRI

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Abstract

Purpose

To evaluate the renal oxygenation in type 2 diabetes by blood oxygenation level dependent magnetic resonance imaging (BOLD-MRI).

Materials and methods

Forty-eight patients with type 2 diabetes and 67 healthy controls were recruited. All patients were further divided into four subgroups based on renal functional level. Bilateral renal cortical R2* (CR2*) and medullary R2* (MR2*) values were extracted and quantified on BOLD-MRI, then R2* ratio between medulla and cortex (MCR) was calculated. CR2*, MR2* and MCR were compared among the groups separately. The relationships were analyzed between R2* values and clinical index of renal function.

Results

Compared with controls, MR2* and CR2* in diabetes were significantly increased. The positive relationship was found between MR2* and estimated glomerular filtration rate (eGFR), and CR2* was negatively correlated with eGFR. Interestingly, the MCR increased in early stage of diabetes and decreased along with the aggravation of diabetic nephropathy (DN).

Conclusion

BOLD-MRI can non-invasively detect and assess the renal hypoxia in diabetes. Our findings suggest that hypoxia in medulla is more apparent and earlier than in cortex. During the progression of DN, a reversion of corticomedullary oxygenation gradient can be detected, thus, MCR would be adopted to suppose the progression and prognosis of DN.

Introduction

Till now the type 2 diabetes is more and more prevalent, and diabetic nephropathy (DN) has become the most leading cause of end-stage renal disease (ESRD) [1], [2]. The onset of DN is insidious, once get into clinical phase, renal function deteriorate progressively. In recent years, many studies focused on the change of renal oxygenation in diabetes and showed renal hypoxia especially in medulla. However, these findings predominantly derived from animal models of experimental diabetes obtained by invasive methods [3], [4]. In 1990s, the concept of “BOLD” was introduced to investigate the tissue oxygenation in vivo non-invasively. Prasad et al. [5] pioneered the application to observe the regulation of renal oxygenation, validated its feasibility under normal conditions and during physiological and pharmacological manoeuvres. Blood oxygenation level dependent (BOLD) MRI uses deoxyhemoglobin which is paramagnetic as an endogenous contrast agent. Deoxygenated hemoglobin causes perturbations in microscopic field gradients in the vicinity of red blood cells and vessels, leading to signal attenuation on T2*(apparent spin–spin relaxation time)-weighted MR images. So increase of transverse relaxation rate R2* (1/T2*) reflect a poor oxygen content in tissue [6], [7]. dos Santos et al. [8] reported that BOLD-MRI could detect hypoxic changes as early as 2 days in streptozotocin-induced diabetes rat kidneys, and the changes were verified by measuring medullary pO2 and blood flow using invasive microprobes. Prasad et al. [9] documented the renal hypoxia in a mouse model of diabetes by BOLD-MRI, which cannot be detected using pimonidazole, a dye used to examine tissue hypoxia in kidney sections. These findings suggested that BOLD-MRI can provide a sensitive method to describe renal hypoxia. Some other confirmed the reproducibility of BOLD measurements in human kidney [10]. A study in humans showed that in the healthy, water-diuresis led to a significant increase in the oxygenation of the renal medulla, but negative result was found in the mild diabetic patients as evaluated by BOLD-MRI [11]. The result suggested that even patients with mild diabetes already showed signs of renal injury. However, the BOLD-MRI feature in DN is unclear.

To our knowledge, the present study was the first time to research renal oxygenation in human diabetic nephropathy with different levels of renal function in a relative bigger sample. The aim was to explore the value of BOLD-MRI in early detection and classification of renal impairment in type 2 diabetes, thereby, provide a new biomarker to guide clinical treatment and imply prognosis.

Section snippets

Subjects

This study was approved by ethics committee of our institution and written informed consent was obtained from all subjects after detailed explanations. Fifty-four type 2 diabetic patients were recruited between December 2009 and September 2010 from clinic and in-patient department of our hospital. All patients were diagnosed as type 2 diabetes by specialists according to the criteria of American diabetes Association in 1997, and without nephropathy caused by any other disease apart from

Results

All of the subjects could successfully complete the whole MR scan. None of them complained about malaise or sickness. After images reviewed, eight subjects had been excluded as a result of bad breath-hold or substantial artifacts. The images of forty-eight patients and sixty-seven healthy volunteers were shown good image quality, and adopted for following analysis. Basic clinical data of subjects are summarized in Table 1. For each subject, five R2* images were calculated by in-house software.

Discussion

In the present study, BOLD-MRI was used to assess the renal oxygenation in controls and patients with type 2 diabetes non-invasively. Our results showed the R2* value was considerably lower in cortex than that in medulla, which was consistent with previous reports [12]. Moreover, higher R2* value can be detected in renal cortex and more apparent in medulla in the kidney of diabetic patients, which implicated the renal hypoxia of the disease. This finding was consistent with changes studied in

Conclusion

In conclusion, our study demonstrates that BOLD-MRI is a valuable method to monitor and assess the renal hypoxia in diabetes. The hypoxia in medulla is more apparent and earlier than that in cortex, which is presumably an important mechanism in the initiation and progression of DN. The parameter of MCR derived from this technique would presumably provide a biomarker for clinical treatment and imply prognosis of DN.

Conflict of interest

This work has no conflict of interest with others.

Acknowledgments

The authors thank Dr. Zhiwei Guo and Dr. Cheng Luo, Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China, for their assistance of data processing.

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