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      Urine metabolomic analysis to detect metabolites associated with the development of contrast induced nephropathy

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      https://www.riss.kr/link?id=A106842503

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      다국어 초록 (Multilingual Abstract)

      Objective Contrast induced nephropathy (CIN) is a result of injury to the proximal tubules. The incidence of CIN is around 11% for imaging done in the acute care setting. We aim to analyze the metabolic patterns in the urine, before and after dosing w...

      Objective Contrast induced nephropathy (CIN) is a result of injury to the proximal tubules. The incidence of CIN is around 11% for imaging done in the acute care setting. We aim to analyze the metabolic patterns in the urine, before and after dosing with intravenous contrast for computed tomography (CT) imaging of the chest, to determine if metabolomic changes exist in patients who develop CIN.
      Methods A convenience sample of high risk patients undergoing a chest CT with intravenous contrast were eligible for enrollment. Urine samples were collected prior to imaging and 4 to 6 hours post imaging. Samples underwent gas chromatography/mass spectrometry profiling. Peak metabolite values were measured and data was log transformed. Significance analysis of microarrays and partial least squares was used to determine the most significant metabolites prior to CT imaging and within subject. Analysis of variance was used to rank metabolites associated with temporal change and CIN. CIN was defined as an increase in serum creatinine level of ≥ 0.5 mg/dL or ≥ 25% above baseline within 48 hours after contrast administration.
      Results We sampled paired urine samples from 63 subjects. The incidence of CIN was 6/63 (9.5%). Patients without CIN had elevated urinary citric acid and taurine concentrations in the pre-CT urine. Xylulose increased in the post CT sample in patients who developed CIN.
      Conclusion Differences in metabolomics patterns in patients who do and do not develop CIN exist. Metabolites may be potential early identifiers of CIN and identify patients at high-risk for developing this condition prior to imaging.

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      참고문헌 (Reference)

      1 Diercks DB, "metabolomic analysis to detect changes after intravenous, non-ionic, low osmolar iodinated radiocontrast for computerized tomographic imaging" 15 : 152-157, 2014

      2 Rauch D, "Variable effects of iodinated contrast media on different rabbit arteries in vitro" 25 (25): S21-S23, 1997

      3 Thomsen HS, "Urine profiles and kidney histology after ionic and nonionic radiologic and magnetic resonance contrast media in rats with cisplatin nephropathy" 2 : 675-682, 1995

      4 Parvez Z, "Urinary adenosine deaminase binding protein, a marker of contrast media induced acute renal damage" 190 : 111-113, 1990

      5 Zhang Y, "The serial effect of iodinated contrast media on renal hemodynamics and oxygenation as evaluated by ASL and BOLD MRI" 7 : 418-425, 2012

      6 Englard S, "The biochemical functions of ascorbic acid" 6 : 365-406, 1986

      7 Nikiforova VJ, "Systems rebalancing of metabolism in response to sulfur deprivation, as revealed by metabolome analysis of Arabidopsis plants" 138 : 304-318, 2005

      8 Jakobsen JA, "Renal tubular effects of diuretics and X-ray contrast media. A comparative study of equimolar doses in healthy volunteers" 28 : 319-324, 1993

      9 Jakobsen JA, "Renal effects of nonionic contrast media after cardioangiography" 35 : 191-196, 1994

      10 Jakobsen JA, "Renal effects of iodixanol in healthy volunteers and patients with severe renal failure" 399 : 191-195, 1995

      1 Diercks DB, "metabolomic analysis to detect changes after intravenous, non-ionic, low osmolar iodinated radiocontrast for computerized tomographic imaging" 15 : 152-157, 2014

      2 Rauch D, "Variable effects of iodinated contrast media on different rabbit arteries in vitro" 25 (25): S21-S23, 1997

      3 Thomsen HS, "Urine profiles and kidney histology after ionic and nonionic radiologic and magnetic resonance contrast media in rats with cisplatin nephropathy" 2 : 675-682, 1995

      4 Parvez Z, "Urinary adenosine deaminase binding protein, a marker of contrast media induced acute renal damage" 190 : 111-113, 1990

      5 Zhang Y, "The serial effect of iodinated contrast media on renal hemodynamics and oxygenation as evaluated by ASL and BOLD MRI" 7 : 418-425, 2012

      6 Englard S, "The biochemical functions of ascorbic acid" 6 : 365-406, 1986

      7 Nikiforova VJ, "Systems rebalancing of metabolism in response to sulfur deprivation, as revealed by metabolome analysis of Arabidopsis plants" 138 : 304-318, 2005

      8 Jakobsen JA, "Renal tubular effects of diuretics and X-ray contrast media. A comparative study of equimolar doses in healthy volunteers" 28 : 319-324, 1993

      9 Jakobsen JA, "Renal effects of nonionic contrast media after cardioangiography" 35 : 191-196, 1994

      10 Jakobsen JA, "Renal effects of iodixanol in healthy volunteers and patients with severe renal failure" 399 : 191-195, 1995

      11 Wang YX, "Radiographic contrast media induced nephropathy: experimental observations and the protective effect of calcium channel blockers" 74 : 1103-1108, 2001

      12 Weisberg LS, "Radiocontrast-induced nephropathy in humans: role of renal vasoconstriction" 41 : 1408-1415, 1992

      13 Hizoh I, "Radiocontrast-induced DNA fragmentation of renal tubular cells in vitro: role of hypertonicity" 13 : 911-918, 1998

      14 Weinberg JM, "Protection by glycine of proximal tubules from injury due to inhibitors of mitochondrial ATP production" 258 (258): C1127-C1140, 1990

      15 Tumlin J, "Pathophysiology of contrast-induced nephropathy" 98 : 14K-20K, 2006

      16 Wright PA, "Nitrogen excretion: three end products, many physiological roles" 198 (198): 273-281, 1995

      17 Freeman RV, "Nephropathy requiring dialysis after percutaneous coronary intervention and the critical role of an adjusted contrast dose" 90 : 1068-1073, 2002

      18 Schad M, "Metabolic profiling of laser microdissected vascular bundles of Arabidopsis thaliana" 1 : 2-, 2005

      19 Weinberg JM, "Metabolic aspects of protection by glycine against hypoxic injury to isolated proximal tubules" 1 : 949-958, 1991

      20 Xia J, "MetaboAnalyst 2.0: a comprehensive server for metabolomic data analysis" 40 : W127-W133, 2012

      21 Bartholomew BA, "Impact of nephropathy after percutaneous coronary intervention and a method for risk stratification" 93 : 1515-1519, 2004

      22 Pezzotti F, "Enzymatic synthesis of aldonic acids" 341 : 2290-2292, 2006

      23 Liss P, "Effects of contrast media and mannitol on renal medullary blood flow and red cell aggregation in the rat kidney" 49 : 1268-1275, 1996

      24 Heyman SN, "Early renal medullary hypoxic injury from radiocontrast and indomethacin" 40 : 632-642, 1991

      25 Weckwerth W, "Differential metabolic networks unravel the effects of silent plant phenotypes" 101 : 7809-7814, 2004

      26 Kaneko K, "Differences in renal tubular toxicity of high- and low-osmolality contrast media" 51 : 579-580, 1989

      27 Weinberg JM, "Cytoprotective effects of glycine and glutathione against hypoxic injury to renal tubules" 80 : 1446-1454, 1987

      28 Mehran R, "Contrast-induced nephropathy: definition, epidemiology, and patients at risk" 100 : S11-S15, 2006

      29 Mitchell AM, "Contrast nephropathy following computed tomography angiography of the chest for pulmonary embolism in the emergency department" 5 : 50-54, 2007

      30 Messana JM, "Comparison of toxicity of radiocontrast agents to renal tubule cells in vitro" 12 : 75-82, 1990

      31 Rauch D, "Comparison of iodinated contrast media-induced renal vasoconstriction in human, rabbit, dog, and pig arteries" 32 : 315-319, 1997

      32 Palm F, "Altered response in renal blood flow and oxygen tension to contrast media in diabetic rats" 44 : 347-353, 2003

      33 McCullough PA, "Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality" 103 : 368-375, 1997

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