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      When Foots Come First: Early Signs of Podocyte Injury in Fabry Nephropathy Without Proteinuria

      editorial
      a , a, b , *
      Nephron
      S. Karger AG

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          Most cited references16

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          Podocyte biology and response to injury.

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            The podocyte's response to stress: the enigma of foot process effacement.

            Progressive loss of podocytes is the most frequent cause accounting for end-stage renal failure. Podocytes are complex, terminally differentiated cells incapable of replicating. Thus lost podocytes cannot be replaced by proliferation of neighboring undamaged cells. Moreover, podocytes occupy a unique position as epithelial cells, adhering to the glomerular basement membrane (GBM) only by their processes, whereas their cell bodies float within the filtrate in Bowman's space. This exposes podocytes to the danger of being lost by detachment as viable cells from the GBM. Indeed, podocytes are continually excreted as viable cells in the urine, and the rate of excretion dramatically increases in glomerular diseases. Given this situation, it is likely that evolution has developed particular mechanisms whereby podocytes resist cell detachment. Podocytes respond to stress and injury by undergoing tremendous changes in shape. Foot process effacement is the most prominent and, yet in some ways, the most enigmatic of those changes. This review summarizes the various structural responses of podocytes to injury, focusing on foot process effacement and detachment. We raise the hypothesis that foot process effacement represents a protective response of podocytes to escape detachment from the GBM.
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              Agalsidase benefits renal histology in young patients with Fabry disease.

              The effect of early-onset enzyme replacement therapy on renal morphologic features in Fabry disease is largely unknown. Here, we evaluated the effect of 5 years of treatment with agalsidase alfa or agalsidase beta in 12 consecutive patients age 7-33 years (median age, 16.5 years). We performed renal biopsies at baseline and after 5 years of enzyme replacement therapy; 7 patients had additional biopsies after 1 and 3 years. After a median of 65 months, biopsy findings from all patients showed total clearance of glomerular endothelial and mesangial cell inclusions, and findings from 2 patients showed complete clearance of inclusions from epithelial cells of the distal tubule. The 4 patients who received the highest dose of agalsidase exhibited substantial clearance of podocyte inclusions, and the youngest patient had nearly complete clearance of these inclusions. Linear regression analysis showed a highly significant correlation between podocyte globotriaocylceramide clearance and cumulative agalsidase dose (r=0.804; P=0.002). Microalbuminuria normalized in five patients. In summary, long-term enzyme replacement therapy in young patients can result in complete globotriaocylceramide clearance of mesangial and glomerular endothelial cells across all dosage regimens, and clearance of podocyte inclusions is dose-dependent.
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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                2015
                January 2015
                15 January 2015
                : 129
                : 1
                : 3-5
                Affiliations
                aNephrology and Dialysis Unit, Meyer Children's Hospital and bDepartment of Biomedical Experimental and Clinical Sciences ‘Mario Serio', University of Florence, Florence, Italy
                Author notes
                *Dr. Paola Romagnani, Department of Biomedical Experimental and, Clinical Sciences ‘Mario Serio', University of Florence, Viale Pieraccini 6, IT-50139 Firenze (Italy), E-Mail p.romagnani@dfc.unifi.it, p.romagnani@meyer.it
                Article
                369307 Nephron 2015;129:3-5
                10.1159/000369307
                25592473
                7c17d780-3e12-4b54-9f25-ab6cdf496991
                © 2015 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
                References: 23, Pages: 3
                Categories
                Clinical Practice: Editorial

                Cardiovascular Medicine,Nephrology
                Cardiovascular Medicine, Nephrology

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