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      Serum Cystatin C, Klotho, and Neutrophil Gelatinase-Associated Lipocalin in the Risk Prediction of Acute Kidney Injury after Acute Myocardial Infarction


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          Background: Patients with acute myocardial infarction (AMI) are at high risk for acute kidney injury (AKI). Novel biomarkers that can predict AKI after AMI may facilitate immediate interventions. Recently, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and klotho have been established as novel AKI biomarkers. However, their effects have not been studied in patients presenting with AMI. In this study, we will measure the serum levels of these three biomarkers to find reliable biomarkers for early diagnosis of AKI in AMI patients. Methods: This prospective observational cohort study was conducted between May 2016 and November 2017. A total of 285 consecutive patients with AMI were enrolled. The study was approved by the institutional review board of Peking University People’s Hospital (No. 2016PHB 042-01). AKI was defined according to the KDIGO criteria in 2012. At admission, the clinical data of patients was collected and serum levels of several AKI biomarkers, including cystatin C, NGAL, and klotho, were measured by ELISA. The relationship between biomarker levels of AKI were analyzed and their discrimination performances were compared. Results: AKI incidence was 17.5% (50/285) during hospitalization. Compared to patients without AKI, the AKI group had higher mortality (20.0% vs. 0.4%, p < 0.001) and tended to be older, had higher incidence of chronic kidney disease, severe cardiac function, more cardiac complications, larger doses of diuretics, and less use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker and statins. Moreover, AKI patients experienced an increase in serum cystatin C (3,709.2 ± 2,281.5 vs. 1,918.5 ± 1,140.6 ng/mL, p < 0.001), NGAL (118.0 ± 70.3 vs. 91.8 ± 52.3 ng/mL, p = 0.003), and klotho (742.2 ± 497.4 vs. 470.3 ± 257.2 pg/mL, p <0.001). Furthermore, the areas under the receiver operating curves demonstrated that serum cystatin C levels at admission had modest discriminative powers for predicting AKI after AMI compared with serum creatinine (0.899, 95% CI, 0.855–0.944 vs. 0.734, 95% CI, 0.649–0.819, p <0.001). There was no difference between the discrimination performances of serum creatinine, NGAL, and klotho. Conclusion: Elevated cystatin C levels are associated with AKI in patients with AMI. This study provides reliable evidence that cystatin C levels may be superior to serum creatinine for predicting AKI after AMI at admission.

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          Most cited references24

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          Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline.

          The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed clinical practice guidelines in 2012 to provide guidance on the evaluation, management, and treatment of chronic kidney disease (CKD) in adults and children who are not receiving renal replacement therapy. The KDIGO CKD Guideline Development Work Group defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence that had been summarized by an evidence review team. Searches of the English-language literature were conducted through November 2012. Final modification of the guidelines was informed by the KDIGO Board of Directors and a public review process involving registered stakeholders. The full guideline included 110 recommendations. This synopsis focuses on 10 key recommendations pertinent to definition, classification, monitoring, and management of CKD in adults.
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            Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective.

            Klotho is an antiaging substance with pleiotropic actions including regulation of mineral metabolism. It is highly expressed in the kidney and is present in the circulation and urine but its role in acute kidney injury (AKI) is unknown. We found that ischemia-reperfusion injury (IRI) in rodents reduced Klotho in the kidneys, urine, and blood, all of which were restored upon recovery. Reduction in kidney and plasma Klotho levels were earlier than that of neutrophil gelatinase-associated lipocalin (NGAL), a known biomarker of kidney injury. Patients with AKI were found to have drastic reductions in urinary Klotho. To examine whether Klotho has a pathogenic role, we induced IRI in mice with different endogenous Klotho levels ranging from heterozygous Klotho haploinsufficient, to wild-type (WT), to transgenic mice overexpressing Klotho. Klotho levels in AKI were lower in haploinsufficient and higher in transgenic compared with WT mice. The haploinsufficient mice had more extensive functional and histological alterations compared with WT mice, whereas these changes were milder in overexpressing transgenic mice, implying that Klotho is renoprotective. Rats with AKI given recombinant Klotho had higher Klotho protein, less kidney damage, and lower NGAL than rats with AKI given vehicle. Hence, AKI is a state of acute reversible Klotho deficiency, low Klotho exacerbates kidney injury and its restoration attenuates renal damage and promotes recovery from AKI. Thus, endogenous Klotho not only serves as an early biomarker for AKI but also functions as a renoprotective factor with therapeutic potential.
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              Contemporary incidence, predictors, and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions: insights from the NCDR Cath-PCI registry.

              This study sought to examine the contemporary incidence, predictors and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions. Acute kidney injury (AKI) is a serious and potentially preventable complication of percutaneous coronary interventions (PCIs) that is associated with adverse outcomes. The contemporary incidence, predictors, and outcomes of AKI are not well defined, and clarifying these can help identify high-risk patients for proactive prevention. A total of 985,737 consecutive patients underwent PCIs at 1,253 sites participating in the National Cardiovascular Data Registry Cath-PCI registry from June 2009 through June 2011. AKI was defined on the basis of changes in serum creatinine level in the hospital according to the Acute Kidney Injury Network (AKIN) criteria. Using multivariable regression analyses with generalized estimating equations, we identified patient characteristics associated with AKI. Overall, 69,658 (7.1%) patients experienced AKI, with 3,005 (0.3%) requiring new dialysis. On multivariable analyses, the factors most strongly associated with development of AKI included ST-segment elevation myocardial infarction (STEMI) presentation (odds ratio [OR]: 2.60; 95% confidence interval [CI]: 2.53 to 2.67), severe chronic kidney disease (OR: 3.59; 95% CI: 3.47 to 3.71), and cardiogenic shock (OR: 2.92; 95% CI: 2.80 to 3.04). The in-hospital mortality rate was 9.7% for patients with AKI and 34% for those requiring dialysis compared with 0.5% for patients without AKI (p < 0.001). After multivariable adjustment, AKI (OR: 7.8; 95% CI: 7.4 to 8.1, p < 0.001) and dialysis (OR: 21.7; 95% CI: 19.6 to 24.1; p < 0.001) remained independent predictors of in-hospital mortality. Approximately 7% of patients undergoing a PCI experience AKI, which is strongly associated with in-hospital mortality. Defining strategies to minimize the risk of AKI in patients undergoing PCI are needed to improve the safety and outcomes of the procedure. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

                Author and article information

                Cardiorenal Med
                Cardiorenal Medicine
                S. Karger AG
                December 2020
                05 October 2020
                : 10
                : 6
                : 374-381
                Emergency Department, Peking University People’s Hospital, Beijing, China
                Author notes
                *Jihong Zhu, Emergency Department, Peking University People’s Hospital, No. 11 Xizhimen South Street, Beijing 100044 (China), zhujihong64@sina.com
                507387 Cardiorenal Med 2020;10:374–381
                © 2020 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. 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.

                : 15 November 2019
                : 21 March 2020
                Page count
                Figures: 1, Tables: 3, Pages: 8
                Research Article

                Cardiovascular Medicine,Nephrology
                Acute kidney injury,Acute myocardial infarction,Early diagnosis,Cystatin C


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