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      Urinary Biomarkers in Acute Kidney Transplant Dysfunction

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          Abstract

          Background: Acute kidney injury (AKI) is a common medical problem among kidney transplant recipients, which may cause a significant impact on patient and allograft survival. Currently, an allograft biopsy remains the ‘gold standard’ for assessing the cause of impaired kidney function. Limitations of the allograft biopsy include the risk of bleeding, injury to the adjacent viscera, and the possibility of sampling error leading to an inadequate diagnosis. Methods: We conducted a comprehensive review of the literature and main published data that discussed the most relevant biomarkers in acute allograft dysfunction, along with their clinical significance. Results: There have been significant discoveries of several important biomarkers that correlated with biopsy findings, clinical outcomes and possibly graft survival. Conclusion: The discovery of surrogate biomarkers in kidney transplantation is an evolving field of crucial importance that mandates further collaborative efforts.

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          FOXP3: of mice and men.

          Steven Ziegler (2006)
          The immune system has evolved mechanisms to recognize and eliminate threats, as well as to protect against self-destruction. Tolerance to self-antigens is generated through two fundamental mechanisms: (a) elimination of self-reactive cells in the thymus during selection and (b) generation of a variety of peripheral regulatory cells to control self-reactive cells that escape the thymus. It is becoming increasing apparent that a population of thymically derived CD4+ regulatory T cells, exemplified by the expression of the IL-2Ralpha chain, is essential for the maintenance of peripheral tolerance. Recent work has shown that the forkhead family transcription factor Foxp3 is critically important for the development and function of the regulatory T cells. Lack of Foxp3 leads to development of fatal autoimmune lymphoproliferative disease; furthermore, ectopic Foxp3 expression can phenotypically convert effector T cells to regulatory T cells. This review focuses on Foxp3 expression and function and highlights differences between humans and mice regarding Foxp3 regulation.
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            Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production.

            Laura Bottomley, Margaret C. Watson, Maggie N Webb … (2000)
            Dysregulated vascular endothelial growth factor (VEGF) expression has been implicated as a major contributor to the development of a number of common disease pathologies. The aim of this study was to establish the extent of genetic variability within the VEGF gene and to determine whether this genetic variation influenced levels of VEGF protein expression. The promoter region and exon 1 of the VEGF gene were screened for polymorphisms using single-stranded conformation (SSCP) polymorphism analysis and direct PCR-sequencing. We identified 15 novel sequence polymorphisms most of which were rare. Eleven of these polymorphisms were single base substitutions, three were single base insertions and one was a two base deletion. Thirteen of the polymorphisms were located within the promoter and two in the 5' untranslated region (5'UTR) of the gene. We established PCR-RFLP typing systems for ten of the polymorphisms. For the two common polymorphisms at -460 and +405, we developed a combined sequence specific priming (SSP) PCR typing system to determine the cis/trans orientation of each allele and hence, ascertain haplotypes. A significant correlation was observed between lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cell (PBMC) VEGF protein production and genotype for the +405 polymorphism. Copyright 2000 Academic Press.
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              Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation.

              C R Parikh, A. Jani, J. Mishra … (2006)
              Delayed graft function (DGF) due to tubule cell injury frequently complicates deceased donor kidney transplants. We tested whether urinary neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) represent early biomarkers for DGF (defined as dialysis requirement within the first week after transplantation). Urine samples collected on day 0 from recipients of living donor kidneys (n = 23), deceased donor kidneys with prompt graft function (n = 20) and deceased donor kidneys with DGF (n = 10) were analyzed in a double blind fashion by ELISA for NGAL and IL-18. In patients with DGF, peak postoperative serum creatinine requiring dialysis typically occurred 2-4 days after transplant. Urine NGAL and IL-18 values were significantly different in the three groups on day 0, with maximally elevated levels noted in the DGF group (p < 0.0001). The receiver-operating characteristic curve for prediction of DGF based on urine NGAL or IL-18 at day 0 showed an area under the curve of 0.9 for both biomarkers. By multivariate analysis, both urine NGAL and IL-18 on day 0 predicted the trend in serum creatinine in the posttransplant period after adjusting for effects of age, gender, race, urine output and cold ischemia time (p < 0.01). Our results indicate that urine NGAL and IL-18 represent early, predictive biomarkers of DGF.
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                Author and article information

                Journal
                Journal ID (publisher-id): NEC
                Journal ID (nlm-ta): Nephron Clin Pract
                Journal ID (doi): 10.1159/issn.1660-2110
                Title: Nephron Clinical Practice
                Publisher: S. Karger AG
                ISSN (Electronic): 1660-2110
                Publication date Subscription-year: 2011
                Publication date (Print): May 2011
                Publication date (Electronic): 16 December 2010
                Volume: 118
                Issue: 2
                Pages: c173-c181
                Affiliations
                aDivision of Nephrology, Department of Medicine, The Johns Hopkins University, bDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and cNephrology Center of Maryland, Baltimore, Md., USA
                Author notes
                *Nada Alachkar, MD, The Johns Hopkins University School of Medicine, 720 Rutland Ave., Ross 971, Baltimore, MD 21205 (USA), Tel. +1 410 614 9225, Fax +1 410 614 1643, E-Mail nalachk1@jhmi.edu
                Article
                Publisher ID: 321381 Other ID: Nephron Clin Pract 2011;118:c173–c181
                DOI: 10.1159/000321381
                PubMed ID: 21160228
                SO-VID: 4cd74dfd-ff9b-43f1-9f29-818ce1a0b087
                Copyright © © 2010 S. Karger AG, Basel
                License:

                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
                Tables: 3, Pages: 9
                Categories
                Subject: Minireview

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Kidney transplant,Urinary biomarker,Acute rejection,Acute kidney injury
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Kidney transplant, Urinary biomarker, Acute rejection, Acute kidney injury

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