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      A Compendium of Urinary Biomarkers Indicative of Glomerular Podocytopathy

      review-article
      1 , 2 , * , 3
      Pathology Research International
      Hindawi Publishing Corporation

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          Abstract

          It is well known that glomerular podocyte injury and loss are present in numerous nephropathies and that the pathophysiologic consecution of disease hinges upon the fate of the podocyte. While multiple factors play a hand in glomerulopathy progression, basic logic lends that if one monitors the podocyte's status, that may reflect the status of disease. Recent investigations have focused on what one can elucidate from the noninvasive collection of urine, and have proven that certain, specific biomarkers of podocytes can be readily identified via varying techniques. This paper has brought together all described urinary biomarkers of podocyte injury and is made to provide a concise summary of their utility and testing in laboratory and clinical theatres. While promising in the potential that they hold as tools for clinicians and investigators, the described biomarkers require further comprehensive vetting in the form of larger clinical trials and studies that would give their value true weight. These urinary biomarkers are put forth as novel indicators of glomerular disease presence, disease progression, and therapeutic efficacy that in some cases may be more advantageous than the established parameters/measures currently used in practice.

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          Most cited references148

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          NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome.

          Familial idiopathic nephrotic syndromes represent a heterogeneous group of kidney disorders, and include autosomal recessive steroid-resistant nephrotic syndrome, which is characterized by early childhood onset of proteinuria, rapid progression to end-stage renal disease and focal segmental glomerulosclerosis. A causative gene for this disease, NPHS2, was mapped to 1q25-31 and we report here its identification by positional cloning. NPHS2 is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family. We found ten different NPHS2 mutations, comprising nonsense, frameshift and missense mutations, to segregate with the disease, demonstrating a crucial role for podocin in the function of the glomerular filtration barrier.
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            Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome.

            Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal-recessive disorder, characterized by massive proteinuria in utero and nephrosis at birth. In this study, the 150 kb critical region of NPHS1 was sequenced, revealing the presence of at least 11 genes, the structures of 5 of which were determined. Four different mutations segregating with the disease were found in one of the genes in NPHS1 patients. The NPHS1 gene product, termed nephrin, is a 1241-residue putative transmembrane protein of the immunoglobulin family of cell adhesion molecules, which by Northern and in situ hybridization was shown to be specifically expressed in renal glomeruli. The results demonstrate a crucial role for this protein in the development or function of the kidney filtration barrier.
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              Podocyte biology and response to injury.

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                Author and article information

                Journal
                Patholog Res Int
                Patholog Res Int
                PRI
                Pathology Research International
                Hindawi Publishing Corporation
                2090-8091
                2042-003X
                2013
                13 November 2013
                : 2013
                : 782395
                Affiliations
                1Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, MMC 609 Mayo D185, Minneapolis, MN 55455, USA
                2Division of Nephrology, Department of Medicine, Harvard Medical School, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA
                3University of Belgrade School of Medicine, Dr. Subotica 8, 11000 Belgrade, Serbia
                Author notes
                *Miroslav Sekulic: sekul002@ 123456umn.edu

                Academic Editor: Piero Tosi

                Author information
                http://orcid.org/0000-0002-7938-1816
                http://orcid.org/0000-0001-5971-7645
                Article
                10.1155/2013/782395
                3845336
                24327929
                a9851e17-701f-4d25-a0a6-aff02d7bf7bc
                Copyright © 2013 M. Sekulic and S. Pichler Sekulic.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 July 2013
                : 10 September 2013
                Categories
                Review Article

                Pathology
                Pathology

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