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Updated: Jun 20, 2026

Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Expression of sialidase and dystroglycan in human glomerular diseases
Nils P J Vogtländer1, Johan van der Vlag, Marinka A H Bakker
1Department of Nephrology, Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
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.
Insights
Glomerular sialidase expression increases in membranous glomerulopathy (MG), potentially causing charge loss in kidney filters. Dystroglycan expression does not reliably distinguish between minimal change nephropathy and focal segmental glomerulosclerosis.
Area of Science:
- Nephrology
- Glomerular Biology
- Biochemistry
Background:
- Alpha-dystroglycan (alpha-DG) is a key podocyte glycoprotein involved in glomerular filtration.
- Previous studies suggested alpha-DG expression differences could distinguish minimal change nephropathy (MCN) from focal segmental glomerulosclerosis (FSGS).
- Sialic acid, a component of alpha-DG, contributes to the glomerular filter's negative charge; exogenous sialidase causes podocyte damage.
Purpose of the Study:
- To investigate endogenous glomerular sialidase expression in various kidney diseases.
- To re-evaluate dystroglycan expression in these conditions.
- To explore the role of sialidase in glomerular charge abnormalities.
Main Methods:
- Immunofluorescence was used to assess glomerular alpha-DG and sialidase expression in kidney biopsies from patients with MCN, FSGS, lupus nephritis (LN), membranous glomerulopathy (MG), and normal kidney controls (NHK).
- Urinary sialic acid levels were quantified using LC-tandem mass spectrometry.
- Statistical analysis compared expression levels across disease groups.
Main Results:
- Glomerular sialidase expression was significantly increased (3-fold) in membranous glomerulopathy (MG) compared to normal kidneys.
- Elevated urinary sialic acid concentrations were observed in two MG patients.
- No significant changes in alpha-dystroglycan (alpha-DG) expression were found across the studied glomerular diseases, including between MCN and FSGS.
Conclusions:
- Increased endogenous glomerular sialidase in MG may contribute to the loss of negative charge in the glomerular filter.
- Dystroglycan expression is not a reliable biomarker for differentiating between MCN and FSGS.
- These findings highlight a potential role for sialidase in the pathogenesis of glomerular diseases like MG.
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