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      Podocyturia: What is in a name?

      review-article
      Journal of Translational Internal Medicine
      De Gruyter Open
      Glomerular basement membrane, nephron, podocyte, podocyturia, proteinuria

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          Abstract

          The podocyte is a highly differentiated cell located in the outer space of the glomerular basement membrane that deals with many different functions. This phylogenetically preserved cell that is responsible for the virtually absence of proteins in the urine lacks of the capacity to divide under normal conditions. When podocytes receive molecular insults, which normally occur during stress conditions as glomerulonephritis, hyperfiltration or metabolic disturbances, they adapt to the new situation by contracting their actin fibers. This adaptive behavior puts at risk the quality of the plasmatic filtration due to the denudation of the glomerular basement membrane, the potential mesangial inflammation and the appearance of proteinuria; podocytes run the risk of detachment from the basement membrane due to a decrease in the adherence to the surrounding matrix after contraction, a process called foot processes effacement. Podocytes change their shape and under constant mechanical stress they finally detach, rendering the glomerular basement membrane unprotected unless other contiguous podocytes are capable of covering the surface. However, these still anchored podocytes are generally also under the same stress situation and follow the same pathway. Podocyturia refers to the presence of these differentiated cells in the urinary sediment. Noteworthy, the podocytes that are encountered in the urine are viable despite the glomerular hostile environment and the urinary acidity. Podocyturia can precede proteinuria and can aggravate it. Therefore, in diseases that can threaten the glomerular normal environment, the presence and the quantification of urinary podocytes can be of remarkable relevance, as it can herald or accompany the appearance of proteinuria, and could offer another view to the interpretation and clinical approach and outcome of proteinuria. However, its identification needs a wide-spread training among biochemists and technicians, as well as commercially available kits.

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          Most cited references42

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          Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases.

          Kidney disease affects over 20 million people in the United States alone. Although the causes of renal failure are diverse, the glomerular filtration barrier is often the target of injury. Dysregulation of VEGF expression within the glomerulus has been demonstrated in a wide range of primary and acquired renal diseases, although the significance of these changes is unknown. In the glomerulus, VEGF-A is highly expressed in podocytes that make up a major portion of the barrier between the blood and urinary spaces. In this paper, we show that glomerular-selective deletion or overexpression of VEGF-A leads to glomerular disease in mice. Podocyte-specific heterozygosity for VEGF-A resulted in renal disease by 2.5 weeks of age, characterized by proteinuria and endotheliosis, the renal lesion seen in preeclampsia. Homozygous deletion of VEGF-A in glomeruli resulted in perinatal lethality. Mutant kidneys failed to develop a filtration barrier due to defects in endothelial cell migration, differentiation, and survival. In contrast, podocyte-specific overexpression of the VEGF-164 isoform led to a striking collapsing glomerulopathy, the lesion seen in HIV-associated nephropathy. Our data demonstrate that tight regulation of VEGF-A signaling is critical for establishment and maintenance of the glomerular filtration barrier and strongly supports a pivotal role for VEGF-A in renal disease.
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            Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys.

            Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell-specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24+CD133+ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.
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              Modification of kidney barrier function by the urokinase receptor.

              Podocyte dysfunction, represented by foot process effacement and proteinuria, is often the starting point for progressive kidney disease. Therapies aimed at the cellular level of the disease are currently not available. Here we show that induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via a mechanism that includes lipid-dependent activation of alphavbeta3 integrin. Mice lacking uPAR (Plaur-/-) are protected from lipopolysaccharide (LPS)-mediated proteinuria but develop disease after expression of a constitutively active beta3 integrin. Gene transfer studies reveal a prerequisite for uPAR expression in podocytes, but not in endothelial cells, for the development of LPS-mediated proteinuria. Mechanistically, uPAR is required to activate alphavbeta3 integrin in podocytes, promoting cell motility and activation of the small GTPases Cdc42 and Rac1. Blockade of alphavbeta3 integrin reduces podocyte motility in vitro and lowers proteinuria in mice. Our findings show a physiological role for uPAR signaling in the regulation of kidney permeability.
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                Author and article information

                Journal
                J Transl Int Med
                J Transl Int Med
                Journal of Translational Internal Medicine
                De Gruyter Open
                2450-131X
                2224-4018
                Apr-Jun 2015
                30 June 2015
                : 3
                : 2
                : 51-56
                Affiliations
                Nephrology and Kidney Transplant Unit, Department of Medicine, Hospital Británico de Buenos Aires, Buenos Aires, Argentina
                Author notes
                Address for Correspondence: Dr. Hernán Trimarchi. Servicio de Nefrología, Hospital Británico de Buenos Aires, Perdriel 74 (1280) Buenos Aires, Argentina. E-mail: htrimarchi@ 123456hotmail.com
                Article
                jtim-2015-0003
                10.1515/jtim-2015-0003
                4936448
                27847887
                00e970a4-baa8-49ae-92c2-585119b0f2d4
                Copyright © International Society of Translational Sciences

                This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License (CC BY-NC-ND 3.0)

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                Categories
                Review Article

                glomerular basement membrane,nephron,podocyte,podocyturia,proteinuria

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