Journal Mobile Options
Table of Contents
Vol. 104, No. 4, 2006
Issue release date: November 2006
Section title: Original Paper
Nephron Exp Nephrol 2006;104:e158–e168
(DOI:10.1159/000094967)

Beneficial Effect of TGFβ Antagonism in Treating Diabetic Nephropathy Depends on When Treatment Is Started

Benigni A. · Zoja C. · Campana M. · Corna D. · Sangalli F. · Rottoli D. · Gagliardini E. · Conti S. · Ledbetter S. · Remuzzi G.
aMario Negri Institute for Pharmacological Research, Bergamo, Italy; bGenzyme Corporation, Framingham, Mass., USA, and cUnit of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy

Do you have an account?

Register and profit from personalized services (MyKarger) Login Information

Please create your User ID & Password





Contact Information









I have read the Karger Terms and Conditions and agree.

Register and profit from personalized services (MyKarger) Login Information

Please create your User ID & Password





Contact Information









I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger (new!)
  • Unrestricted printing, no saving restrictions for personal use
  • Reduced rates with a PPV account
read more

Direct: USD 38.00
Account: USD 26.50

Select

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe

  • Automatic perpetual access to all articles of the subscribed year(s)
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 2/2/2006
Accepted: 4/26/2006
Published online: 8/11/2006

Number of Print Pages: 1
Number of Figures: 5
Number of Tables: 2

ISSN: (Print)
eISSN: 1660-2129 (Online)

For additional information: http://www.karger.com/NEE

Abstract

Background: In diabetic rats with maximal activation of RAS induced by uninephrectomy, late treatment with anti-TGFβ antibody limited renal injury only when combined with ACE inhibitor. We investigated whether in a two-kidney diabetic model the time at which treatment started predicted the response to TGFβ antagonist. Methods: 27 weeks after streptozotocin injection, animals had mild proteinuria and were randomized to receive irrelevant antibody, anti-TGFβ antibody (1D11) or enalapril till 52 weeks (early treatment). The effect of agents alone or combined was also evaluated at the time of overt proteinuria (late treatment, 52–61 weeks). Results: When given early, 1D11 displayed marked antihypertensive and antiproteinuric effects. Glomerulosclerosis was reduced to the extent that a remarkable percentage of glomeruli without sclerosis appeared after treatment. Podocyte number was normalized. Renoprotection of 1D11 was comparable to enalapril. Despite control of blood pressure, in late treatment single agents did not reduce proteinuria significantly. Glomerulosclerosis and podocyte loss were partially limited by 1D11 or enalapril, but full protection was achieved by combination. Conclusions: Renoprotective effect of TGFβ antagonism crucially depends on the time at which treatment started. Effectiveness of early treatment with 1D11 would indicate that TGFβ is a major mediator of damage in early diabetes. To tackle the renal damage in the phase of advanced disease, a combined treatment with ACE inhibitor is needed.


  

Author Contacts

Ariela Benigni, PhD
‘Mario Negri’ Institute for Pharmacological Research
Via Gavazzeni, 11, 24125 Bergamo (Italy)
Tel. +39 035 319 888, Fax +39 035 319 331
E-Mail abenigni@marionegri.it

  

Article Information

Received: February 2, 2006
Accepted: April 26, 2006
Published online: August 10, 2006
Number of Print Pages : 11
Number of Figures : 5, Number of Tables : 2, Number of References : 51

  

Publication Details

Nephron Experimental Nephrology

Vol. 104, No. 4, Year 2006 (Cover Date: November 2006)

Journal Editor: Woolf, A.S. (London)
ISSN: 1660–2129 (print), 1660–2129 (Online)

For additional information: http://www.karger.com/NEE


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 2/2/2006
Accepted: 4/26/2006
Published online: 8/11/2006

Number of Print Pages: 1
Number of Figures: 5
Number of Tables: 2

ISSN: (Print)
eISSN: 1660-2129 (Online)

For additional information: http://www.karger.com/NEE


Copyright / Drug Dosage

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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.