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      High Temporal Resolution Parametric MRI Monitoring of the Initial Ischemia/Reperfusion Phase in Experimental Acute Kidney Injury

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          Abstract

          Ischemia/reperfusion (I/R) injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI). There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive in vivo parametric magnetic resonance imaging (MRI) may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T 2* and T 2, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T 2*/T 2 mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T 2* and T 2 were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.

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          Most cited references27

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          Acute kidney injury, mortality, length of stay, and costs in hospitalized patients.

          The marginal effects of acute kidney injury on in-hospital mortality, length of stay (LOS), and costs have not been well described. A consecutive sample of 19,982 adults who were admitted to an urban academic medical center, including 9210 who had two or more serum creatinine (SCr) determinations, was evaluated. The presence and degree of acute kidney injury were assessed using absolute and relative increases from baseline to peak SCr concentration during hospitalization. Large increases in SCr concentration were relatively rare (e.g., >or=2.0 mg/dl in 105 [1%] patients), whereas more modest increases in SCr were common (e.g., >or=0.5 mg/dl in 1237 [13%] patients). Modest changes in SCr were significantly associated with mortality, LOS, and costs, even after adjustment for age, gender, admission International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis, severity of illness (diagnosis-related group weight), and chronic kidney disease. For example, an increase in SCr >or=0.5 mg/dl was associated with a 6.5-fold (95% confidence interval 5.0 to 8.5) increase in the odds of death, a 3.5-d increase in LOS, and nearly 7500 dollars in excess hospital costs. Acute kidney injury is associated with significantly increased mortality, LOS, and costs across a broad spectrum of conditions. Moreover, outcomes are related directly to the severity of acute kidney injury, whether characterized by nominal or percentage changes in serum creatinine.
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            Pathophysiology of ischemic acute kidney injury.

            Acute kidney injury (AKI) as a consequence of ischemia is a common clinical event leading to unacceptably high morbidity and mortality, development of chronic kidney disease (CKD), and transition from pre-existing CKD to end-stage renal disease. Data indicate a close interaction between the many cell types involved in the pathophysiology of ischemic AKI, which has critical implications for the treatment of this condition. Inflammation seems to be the common factor that links the various cell types involved in this process. In this Review, we describe the interactions between these cells and their response to injury following ischemia. We relate these events to patients who are at high risk of AKI, and highlight the characteristics that might predispose these patients to injury. We also discuss how therapy targeting specific cell types can minimize the initial and subsequent injury following ischemia, thereby limiting the extent of acute changes and, hopefully, long-term structural and functional alterations to the kidney.
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              Recent advances in the pathophysiology of ischemic acute renal failure.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                28 February 2013
                : 8
                : 2
                : e57411
                Affiliations
                [1 ]Berlin Ultrahigh Field Facility, Max Delbrück Center for Molecular Medicine, Berlin, Germany
                [2 ]Nephrology and Intensive Care Medicine, Charité Campus Virchow-Klinikum and Center for Cardiovascular Research, Charité, Berlin, Germany
                [3 ]Institute of Physiology, Center for Cardiovascular Research, Charité-Universitätsmedizin Berlin, Berlin, Germany
                [4 ]Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, Germany
                [5 ]Max Delbrück Center for Molecular Medicine, Berlin, Germany
                Osaka University Graduate School of Medicine, Japan
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: TN ES AP JH MF UH BF WHS DD. Performed the experiments: JH MF GB KA KC. Analyzed the data: JH AP ES KA UH. Contributed reagents/materials/analysis tools: JH AP MF ES UH HW. Wrote the paper: AP TN ES UH DD JH SW.

                Article
                PONE-D-12-40179
                10.1371/journal.pone.0057411
                3585384
                23468984
                88aed07c-96c1-4b04-b21a-f04404bc0f09
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 December 2012
                : 21 January 2013
                Page count
                Pages: 9
                Funding
                This study was supported by the Deutsche Forschungsgemeinschaft (FOR 1368). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Renal System
                Biochemistry
                Metabolism
                Oxygen Metabolism
                Model Organisms
                Animal Models
                Rat
                Medicine
                Anatomy and Physiology
                Renal System
                Renal Circulation
                Nephrology
                Radiology
                Diagnostic Radiology
                Magnetic Resonance Imaging

                Uncategorized
                Uncategorized

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