Radiocontrast nephropathy (RCN) is a third common cause of hospital acquired renal failure, accounting for 11% of incidence. With the continuing rise in the number of diagnostic imaging procedures and because it is a hospital acquired syndrome, the need for prevention is most compelling. However, the mechanisms behind the development of RCN remain not fully understood. Many interventions proposed based on animal testing have failed in human trials. The possible reasons for this disconnect may be due to: (1) animal models not adequately representing the human physiology, (2) outcome measures used in animal models differ from those used in the clinic, (3) invalid hypothesis etc.. Over the last two decades significant progress has been made in terms of understanding the oxygenation status within the kidney and it is now well appreciated that regions within the kidney survive under hypoxic conditions. In order for the kidney to survive in the hypoxic milieu, powerful control mechanisms have evolved that maintain oxygen sufficiency even under the threat of external stimuli such as during administration of contrast media. It is believed that compromise in the ability of the kidney to activate these control mechanisms during a """"""""stress"""""""" may be the cause for the development of renal failure following stimuli such as contrast media. Based on these hypotheses, novel animal models have been proposed and validated. These are simpler compared to previous models that necessitate surgical manipulations, and more importantly better represent the functional aspect of the human condition. Additionally, the techniques available for monitoring intra-renal oxygenation have continuously improved. Blood oxygenation level dependent (BOLD) MRI technique has been shown to be sensitive and efficacious in evaluating renal oxygenation both in rat and human kidneys. In addition, better understanding of the oxygenation status has given rise to new targets for intervention. Based on this background, this proposal extends our present findings in healthy and hypertensive kidneys with BOLD MRI to better understand the acute hemodynamic responses following contrast administration in functional models of RCN and in RCN prone diabetic rats. We will additionally acquire markers that are used in the clinic. We will also test the efficacy of novel interventions targeted at relieving hypoxia. We will further use sodium MRI to monitor acute changes following contrast media and correlate them with BOLD MRI measurements. Successful outcome should have a significant impact on the development of preventive strategies for RCN. Radiocontrast induced renal failure is a common hospital acquired syndrome and because the consequences could be severe including death, preventive strategies are highly sought after. With the continuous increase in the number diagnostic procedures, the relevance and significance of this problem is growing. Our proposed study will allow for better understanding of the mechanisms behind the development of this syndrome and develop novel preventive strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK053221-15
Application #
8208030
Study Section
Special Emphasis Panel (ZRG1-MEDI-A (09))
Program Officer
Rys-Sikora, Krystyna E
Project Start
1998-02-01
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2013-12-31
Support Year
15
Fiscal Year
2012
Total Cost
$325,087
Indirect Cost
$111,915
Name
Northshore University Healthsystem
Department
Type
DUNS #
069490621
City
Evanston
State
IL
Country
United States
Zip Code
60201
Li, Lu-Ping; Lu, Jing; Franklin, Tammy et al. (2015) Effect of iodinated contrast medium in diabetic rat kidneys as evaluated by blood-oxygenation-level-dependent magnetic resonance imaging and urinary neutrophil gelatinase-associated lipocalin. Invest Radiol 50:392-6
Tan, Huan; Thacker, Jon; Franklin, Tammy et al. (2015) Sensitivity of arterial spin labeling perfusion MRI to pharmacologically induced perfusion changes in rat kidneys. J Magn Reson Imaging 41:1124-8
Li, Lu-Ping; Lu, Jing; Zhou, Ying et al. (2014) Evaluation of intrarenal oxygenation in iodinated contrast-induced acute kidney injury-susceptible rats by blood oxygen level-dependent magnetic resonance imaging. Invest Radiol 49:403-10
Li, Lu-Ping; Thacker, Jon; Lu, Jing et al. (2014) Efficacy of preventive interventions for iodinated contrast-induced acute kidney injury evaluated by intrarenal oxygenation as an early marker. Invest Radiol 49:647-52
Li, Lu-Ping; Franklin, Tammy; Du, Hongyan et al. (2012) Intrarenal oxygenation by blood oxygenation level-dependent MRI in contrast nephropathy model: effect of the viscosity and dose. J Magn Reson Imaging 36:1162-7
Storey, Pippa; Ji, Lin; Li, Lu-Ping et al. (2011) Sensitivity of USPIO-enhanced R2 imaging to dynamic blood volume changes in the rat kidney. J Magn Reson Imaging 33:1091-9
Haque, Muhammad; Franklin, Tammy; Prasad, Pottumarthi (2011) Renal oxygenation changes during water loading as evaluated by BOLD MRI: effect of NOS inhibition. J Magn Reson Imaging 33:898-901
Ji, Lin; Li, Lu-Ping; Schnitzer, Thomas et al. (2010) Intra-renal oxygenation in rat kidneys during water loading: effects of cyclooxygenase (COX) inhibition and nitric oxide (NO) donation. J Magn Reson Imaging 32:383-7
Li, Lu-Ping; Ji, Lin; Santos, Elisabete A et al. (2009) Effect of nitric oxide synthase inhibition on intrarenal oxygenation as evaluated by blood oxygenation level-dependent magnetic resonance imaging. Invest Radiol 44:67-73
Li, Lu-Ping; Halter, Sarah; Prasad, Pottumarthi V (2008) Blood oxygen level-dependent MR imaging of the kidneys. Magn Reson Imaging Clin N Am 16:613-25, viii

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