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      Pre-Interventional Kynurenine Predicts Medium-Term Outcome after Contrast Media Exposure Due to Coronary Angiography

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          Abstract

          Background/Aims: Contrast induced acute kidney injury (CI-AKI) remains a serious complication of contrast media enhanced procedures like coronary angiography. There is still a lack of established biomarkers that help to identify patients at high risk for short and long-term complications. The aim of the current study was to evaluate plasma kynurenine as a predictive biomarker for CI-AKI and long-term complications, measured by the combined endpoint "major adverse kidney events" (MAKE) up to 120 days after CM application. Methods: In this prospective cohort study 245 patients undergoing coronary angiography were analyzed. Blood samples were obtained at baseline, 24h and 48h after contrast media (CM) application to diagnose CI-AKI. Patients were followed for 120 days for adverse clinical events including death, the need for dialysis, and a doubling of plasma creatinine. Occurrence of any of these events was summarized in the combined endpoint MAKE. Results: Preinterventional plasma kynurenine was not associated with CI-AKI. Patients who later developed MAKE displayed significantly increased preinterventional plasma kynurenine levels (p<0.0001). ROC analysis revealed that preinterventional kynurenine is highly predictive for MAKE (AUC=0.838; p<0.0001). The optimal cutoff was found at ≥3.5 µmol/L Using this cutoff, the Kaplan-Meier estimator demonstrated that concentrations of plasma kynurenine ≥3.5 µmol/L were significantly associated with a higher prevalence of MAKE until follow up (p<0.0001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. Conclusion: Preinterventional plasma kynurenine might serve as a highly predictive biomarker for MAKE up to 120 days after coronary angiography.

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          Most cited references30

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          A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation.

          We sought to develop a simple risk score of contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI). Although several risk factors for CIN have been identified, the cumulative risk rendered by their combination is unknown. A total of 8,357 patients were randomly assigned to a development and a validation dataset. The baseline clinical and procedural characteristics of the 5,571 patients in the development dataset were considered as candidate univariate predictors of CIN (increase >or=25% and/or >or=0.5 mg/dl in serum creatinine at 48 h after PCI vs. baseline). Multivariate logistic regression was then used to identify independent predictors of CIN with a p value 75 years, anemia, and volume of contrast) were assigned a weighted integer; the sum of the integers was a total risk score for each patient. The overall occurrence of CIN in the development set was 13.1% (range 7.5% to 57.3% for a low [ or=16] risk score, respectively); the rate of CIN increased exponentially with increasing risk score (Cochran Armitage chi-square, p < 0.0001). In the 2,786 patients of the validation dataset, the model demonstrated good discriminative power (c statistic = 0.67); the increasing risk score was again strongly associated with CIN (range 8.4% to 55.9% for a low and high risk score, respectively). The risk of CIN after PCI can be simply assessed using readily available information. This risk score can be used for both clinical and investigational purposes.
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            Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines.

            The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml/min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR ≥ 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally.
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              Association between AKI, recovery of renal function, and long-term outcomes after hospital discharge.

              This study aimed to determine if recovery of kidney function after AKI modifies the association between AKI during hospitalization and adverse outcomes after discharge. The effect of renal recovery after AKI was evaluated in a population-based cohort study (n=190,714) with participants identified from a provincial claims registry in Alberta, Canada, between November 1, 2002 and December 31, 2007. AKI was identified by a two-fold increase between prehospital and peak in-hospital serum creatinine (SCr). Recovery was assessed using SCr drawn closest to 90 days after the AKI event. All-cause mortality and a combined renal outcome of sustained doubling of SCr or progression to kidney failure were evaluated. Overall, 3.7% of the participants (n=7014) had AKI, 62.7% of whom (n=4400) survived 90 days. In the 3231 patients in whom recovery could be assessed over a median follow-up of 34 months, 30.8% (n=1268) of AKI survivors died and 2.1% (n=85) progressed to kidney failure. Participants who did not recover kidney function had a higher risk for mortality and adverse renal outcomes when AKI participants who recovered to within 25% of baseline SCr were used as the reference group (adjusted mortality hazard ratio (HR), 1.26; 95% confidence interval, 1.10, 1.43) (adjusted renal outcomes HR, 4.13; 95% confidence interval, 3.38, 5.04). Mortality HR was notably higher when participants failed to recover within 55% of baseline. Renal recovery after AKI is associated with a lower risk of death or adverse renal outcomes after hospital discharge.
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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2017
                June 2017
                25 May 2017
                : 42
                : 2
                : 244-256
                Affiliations
                [_a] aInstitute of Nutritional Sciences, University of Potsdam, Nuthetal, Germany
                [_b] bCenter for Cardiovascular Research, Berlin, Germany
                [_c] cDepartment of Nephrology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany
                [_d] dInstitut für Laboratoriumsmedizin Berlin, IFLb, Berlin, Germany
                [_e] eNeuroimmun GmbH, Karlsruhe, Germany
                [_f] fDepartment of Cardiology and Angiology, Charité Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
                [_g] gImmundiagnostik AG, Bensheim, Germany
                [_h] hBayer AG, Wuppertal, Germany
                [_i] iDepartment of Basic Medicine, Jinan University, Jinan, China
                Author notes
                *Prof. Dr. Berthold Hocher, University of Potsdam, Institute of Nutritional Science,, Arthur-Scheunert-Allee 114-116,, 14558 Nuthetal, Potsdam (Germany), Tel. 033200/88-5508, Fax 033200/88-5541,E-Mail hocher@uni-potsdam.de, http://www.uni-potsdam.de/eem
                Article
                477222 Kidney Blood Press Res 2017;42:244–256
                10.1159/000477222
                28531884
                bbea4995-c4a4-4e4d-b0d2-4d845f295b79
                © 2017 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 06 February 2017
                : 08 March 2017
                Page count
                Figures: 3, Tables: 5, Pages: 13
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Preinterventional biomarker,Contrast induced acute kidney injury,Major adverse kidney event,Kynurenine,Coronary angiography

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