Noninvasive evaluation of renal oxygenation in diabetic nephropathy by BOLD-MRI
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.
References (28)
- et al.
Molecular mechanism of diabetic nephropathy
Clin Chim Acta
(2000) - et al.
Epidemic of end-stage renal disease in people with diabetes in the United States population: do we know the cause&quest
Kidney Int
(2005) - et al.
Role of hypoxia in the pathogenesis of renal disease
Kidney Int
(2005) - et al.
The role of tubular injury in diabetic nephropathy
Eur J Intern Med
(2009) - et al.
Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy
Kidney Int
(2004) - et al.
Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension
Diabetologia
(2003) - et al.
Noninvasive evaluation of intrarenal oxygenation with BOLD MRI
Circulation
(1996) - et al.
Is assessing renal oxygenation by using blood oxygen level-dependent MR imaging a clinical reality?
Radiology
(2008) - et al.
Bold MRI of the kidneys
Magn Reson Imaging Clin N Am
(2008) - et al.
Early changes with diabetes in renal medullary hemodynamics as evaluated by fiberoptic probes and BOLD magnetic resonance imaging
Invest Radiol
(2007)
Evaluation of renal hypoxia in diabetic mice by BOLD MRI
Invest Radiol
Non-invasive monitoring of renal oxygenation using BOLD-MRI: a reproducibility study
NMR Biomed
Effect of diabetes on renal medullary oxygenation during water diuresis
Diabetes Care
Comparison of 1.5 and 3 T BOLD MR to study oxygenation of kidney cortex and medulla in human renovascular disease
Invest Radiol
Cited by (114)
Anti-hyperglycemic potential of alginate oligosaccharide in a high glucose-induced zebrafish model
2022, Journal of Functional FoodsFunctional MRI in assessment of diabetic kidney disease in people with type 1 diabetes
2022, Journal of Diabetes and its ComplicationsAdvanced non-invasive diagnostic techniques for visualization and estimation of kidney fibrosis
2021, Drug Discovery TodaySodium-Glucose Cotransporter 2 Inhibition: Rationale and Mechanisms for Kidney and Cardiovascular Protection in People With and Without Diabetes
2021, Advances in Chronic Kidney Disease