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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Benefits and Risks of Continuing Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Antagonists, and Mineralocorticoid Receptor Antagonists during Hospitalizations for Acute Heart Failure

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          Abstract

          Background: The renin-angiotensin-aldosterone axis plays a pivotal role in the pathophysiology of acute and chronic heart failure (HF) and represents an important target for guideline-directed medical therapy. Summary: The use of appropriate directed medical therapies for inhibition of the renin-angiotensin-aldosterone axis in chronic HF has been the subject of several landmark clinical trials, with high levels of adherence exhibited in the outpatient setting. However, less clarity exists with respect to the initiation, continuation, and cessation of renin-angiotensin-aldosterone system inhibitors (RAASi) in the setting of acute HF and exacerbation of HF necessitating hospitalization. In this review, we summarize relevant aspects of the physiology of the renin-angiotensin-aldosterone axis in acute HF and during decongestion. We also summarize the available evidence for the risks and benefits of initiating and continuing RAASi in acute HF. Key Message: We offer a decision-making pathway for the use of RAASi in the setting of acute HF that would help guide the cardiologist and nephrologist caring for patients with acute HF and cardiorenal syndrome.

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          Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

          Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P 0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration ClinicalTrials.gov number NCT01209169.
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            Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association

            Cardiorenal syndrome encompasses a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in 1 organ may induce acute or chronic dysfunction in the other organ. It represents the confluence of heart-kidney interactions across several interfaces. These include the hemodynamic cross-talk between the failing heart and the response of the kidneys and vice versa, as well as alterations in neurohormonal markers and inflammatory molecular signatures characteristic of its clinical phenotypes. The mission of this scientific statement is to describe the epidemiology and pathogenesis of cardiorenal syndrome in the context of the continuously evolving nature of its clinicopathological description over the past decade. It also describes diagnostic and therapeutic strategies applicable to cardiorenal syndrome, summarizes cardiac-kidney interactions in special populations such as patients with diabetes mellitus and kidney transplant recipients, and emphasizes the role of palliative care in patients with cardiorenal syndrome. Finally, it outlines the need for a cardiorenal education track that will guide future cardiorenal trials and integrate the clinical and research needs of this important field in the future.
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              Neurohormonal activation in heart failure with reduced ejection fraction

              Heart failure with reduced ejection fraction (HFrEF) develops when cardiac output falls as a result of cardiac injury. The most well-recognized of the compensatory homeostatic responses to a fall in cardiac output are activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS). In the short term, these 'neurohormonal' systems induce a number of changes in the heart, kidneys, and vasculature that are designed to maintain cardiovascular homeostasis. However, with chronic activation, these responses result in haemodynamic stress and exert deleterious effects on the heart and the circulation. Neurohormonal activation is now known to be one of the most important mechanisms underlying the progression of heart failure, and therapeutic antagonism of neurohormonal systems has become the cornerstone of contemporary pharmacotherapy for heart failure. In this Review, we discuss the effects of neurohormonal activation in HFrEF and highlight the mechanisms by which these systems contribute to disease progression.
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                Author and article information

                Journal
                CRM
                Cardiorenal Med
                10.1159/issn.1664-5502
                Cardiorenal Medicine
                S. Karger AG
                1664-3828
                1664-5502
                2020
                March 2020
                14 February 2020
                : 10
                : 2
                : 69-84
                Affiliations
                [_a] aMount Sinai Icahn School of Medicine, New York, New York, USA
                [_b] bEinstein Medical Center, Philadelphia, Pennsylvania, USA
                [_c] cSidney Kimmel College of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
                [_d] dBaylor Heart and Vascular Institute, Dallas, Texas, USA
                [_e] eBaylor Scott & White Research Institute, Dallas, Texas, USA
                [_f] fBaylor University Medical Center, Dallas, Texas, USA
                [_g] gBaylor Heart and Vascular Hospital, Dallas, Texas, USA
                [_h] hTexas A&M College of Medicine Health Science Center, Dallas, Texas, USA
                Author notes
                *Estefania Oliveros, MD, Division of Cardiology, Department of Medicine, Icahn School of Medicine, Mount Sinai Hospital, 1309 5th Avenue Apt 7B, New York, NY 10029 (USA), estefaniaoliveros@gmail.com
                Author information
                https://orcid.org/0000-0001-7088-6677
                Article
                504167 Cardiorenal Med 2020;10:69–84
                10.1159/000504167
                32062648
                c28d1e95-dc3a-45fb-a227-a99c8973ca5d
                © 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.

                History
                : 07 September 2019
                : 12 October 2019
                Page count
                Figures: 6, Tables: 2, Pages: 16
                Categories
                Review Article

                Cardiovascular Medicine,Nephrology
                Acute heart failure,Diuretics,Renin-angiotensin-aldosterone system,Ultrafiltration,Acute kidney injury,Cardiorenal syndrome,Tubular injury biomarkers

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