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NDT Advance Access published online on September 15, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp465
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© The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Expression of sialidase and dystroglycan in human glomerular diseases

Nils P. J. Vogtländer1, Johan van der Vlag1, Marinka A. H. Bakker1, Henry B. Dijkman2, Ron A. Wevers3, Kevin P. Campbell4, Jack F. M. Wetzels1 and Jo H. M. Berden1

1 Department of Nephrology, Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences 2 Department of Pathology 3 Department of Laboratory Medicine, Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 4 Department of Physiology and Biophysics, Howard Hughes Medical Institute, Iowa City, IA, USA

Correspondence and offprint requests to: J. H. M. Berden; E-mail: j.berden{at}nier.umcn.nl



  Abstract

Background. {alpha}-Dystroglycan ({alpha}-DG) is a negatively charged glycoprotein that covers the surface of podocytes. A decreased glomerular expression of {alpha}-DG has been described in minimal change nephropathy (MCN), but not in focal segmental glomerulosclerosis (FSGS). This was suggested as a tool to distinguish these diseases. Sialic acid is a negatively charged carbohydrate extensively present on both {alpha}-DG and podocalyxin, which is also expressed on podocytes. Intrarenal perfusion with bacterial sialidase leads to foot process effacement and proteinuria. This is the first study on the expression of endogenous glomerular sialidase; furthermore, the expression of dystroglycan was re-evaluated.

Methods. The expression of {alpha}-DG and sialidase was investigated by immunofluorescence in kidney biopsies of patients with MCN (n = 5), FSGS (n = 15), proliferative lupus nephritis (LN, n = 9), membranous glomerulopathy (MG, n = 10) and normal human kidneys (NHK, n = 4). The urinary sialic acid concentration was measured using a newly developed LC-tandem mass spectrometry method.

Results. A 3-fold increased glomerular expression of sialidase was found in MG, accompanied with an increased urinary sialic acid concentration in two MG patients. However, we did not observe major changes in the expression of {alpha}-DG in patients with the above-mentioned glomerular diseases compared to NHK, also not between MCN and FSGS.

Conclusions. Endogenous glomerular sialidase expression is increased in MG, which might represent a novel mechanism for the loss of negative charge in the glomerular capillary filter. The expression of dystroglycan cannot be used as a diagnostic tool to differentiate between glomerular diseases.

Keywords: dystroglycan; podocalyxin; podocyte; sialic acid; sialidase

Received for publication: 14.11.08
Accepted in revised form: 14. 8.09


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