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      Biomarkers of Acute Kidney Injury in Different Clinical Settings: A Time to Change the Paradigm?

      review-article
      ,
      Kidney and Blood Pressure Research
      S. Karger AG
      Biomarker, Acute kidney injury, End-stage renal disease

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          Abstract

          Acute kidney injury (AKI) is diagnosed in 5% of all hospitalized patients and in up to 50% of all ICU patients. In the last years a dramatic rise in the prevalence of AKI has been observed with virtually no change in mortality, reaching up to 50–80% in all dialyzed ICU patients. AKI may progress to end-stage renal disease, and even subclinical episodes of AKI, which are common, may also progress to end-stage renal disease. The early detection of AKI may enable timely intervention and prevention of progression; however, in animal models and in human studies the ‘window of therapeutic intervention’ is narrow. Different urinary and serum proteins have been intensively investigated as possible biomarkers for the early diagnosis of AKI. There are promising candidate biomarkers with the ability to detect an early and graded increase in tubular epithelial cell injury and distinguish pre-renal disease from acute tubular necrosis. In this review, new emerging biomarkers of AKI are presented and described in some clinical settings, such as cardiac surgery, contrast-induced nephropathy, delayed graft function and ICU/emergency departments, where biomarkers are urgently needed to diagnose, make prognoses and differentiate.

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          Most cited references81

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          Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease.

          Activation of naive CD4(+) T-helper cells results in the development of at least two distinct effector populations, Th1 and Th2 cells. Th1 cells produce cytokines (interferon (IFN)-gamma, interleukin (IL)-2, tumour-necrosis factor (TNF)-alpha and lymphotoxin) that are commonly associated with cell-mediated immune responses against intracellular pathogens, delayed-type hypersensitivity reactions, and induction of organ-specific autoimmune diseases. Th2 cells produce cytokines (IL-4, IL-10 and IL-13) that are crucial for control of extracellular helminthic infections and promote atopic and allergic diseases. Although much is known about the functions of these two subsets of T-helper cells, there are few known surface molecules that distinguish between them. We report here the identification and characterization of a transmembrane protein, Tim-3, which contains an immunoglobulin and a mucin-like domain and is expressed on differentiated Th1 cells. In vivo administration of antibody to Tim-3 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease, and increases the number and activation level of macrophages. Tim-3 may have an important role in the induction of autoimmune diseases by regulating macrophage activation and/or function.
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            The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition.

            First identified as a neutrophil granule component, neutrophil gelatinase-associated lipocalin (NGAL; also called human neutrophil lipocalin, 24p3, uterocalin, or neu-related lipocalin) is a member of the lipocalin family of binding proteins. Putative NGAL ligands, including neutrophil chemotactic agents such as N-formylated tripeptides, have all been refuted by recent biochemical and structural results. NGAL has subsequently been implicated in diverse cellular processes, but without a characterized ligand, the molecular basis of these functions remained mysterious. Here we report that NGAL tightly binds bacterial catecholate-type ferric siderophores through a cyclically permuted, hybrid electrostatic/cation-pi interaction and is a potent bacteriostatic agent in iron-limiting conditions. We therefore propose that NGAL participates in the antibacterial iron depletion strategy of the innate immune system.
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              Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury.

              We report the identification of rat and human cDNAs for a type 1 membrane protein that contains a novel six-cysteine immunoglobulin-like domain and a mucin domain; it is named kidney injury molecule-1 (KIM-1). Structurally, KIM-1 is a member of the immunoglobulin gene superfamily most reminiscent of mucosal addressin cell adhesion molecule 1 (MAdCAM-1). Human KIM-1 exhibits homology to a monkey gene, hepatitis A virus cell receptor 1 (HAVcr-1), which was identified recently as a receptor for the hepatitis A virus. KIM-1 mRNA and protein are expressed at a low level in normal kidney but are increased dramatically in postischemic kidney. In situ hybridization and immunohistochemistry revealed that KIM-1 is expressed in proliferating bromodeoxyuridine-positive and dedifferentiated vimentin-positive epithelial cells in regenerating proximal tubules. Structure and expression data suggest that KIM-1 is an epithelial cell adhesion molecule up-regulated in the cells, which are dedifferentiated and undergoing replication. KIM-1 may play an important role in the restoration of the morphological integrity and function to postischemic kidney.
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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
                2010
                November 2010
                01 October 2010
                : 33
                : 5
                : 368-382
                Affiliations
                Department of Nephrology and Transplantology, Medical University, Bialystok, Poland
                Author notes
                *Prof. Jolanta Malyszko, Department of Nephrology and Transplantology, Medical University, Zurawia 14, PL–15-540 Bialystok (Poland), Tel. +48 857 409 464, E-Mail jolmal@poczta.onet.pl
                Article
                319505 Kidney Blood Press Res 2010;33:368–382
                10.1159/000319505
                20924195
                eeac0c6c-98ac-473c-adf9-ec6a908da48e
                © 2010 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
                Page count
                Figures: 6, References: 112, Pages: 15
                Categories
                Review

                Cardiovascular Medicine,Nephrology
                Acute kidney injury,Biomarker,End-stage renal disease
                Cardiovascular Medicine, Nephrology
                Acute kidney injury, Biomarker, End-stage renal disease

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