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Does vascular endothelial growth factor (VEGF) play a role in the pathogenesis of minimal change disease?
Geoffrey Boner1, Alison J Cox, Darren J Kelly
1Baker Medical Research Institute, St Kilda Central, Melbourne, Australia. gboner@post.tau.ac.il
Background:
Minimal change disease (MCD) is one of the major causes of nephrotic syndrome both in children and adults. The pathogenesis of this condition is not clear and it has been suggested that a plasma permeability factor may play a role. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, has been thought to be one the factors involved. The aim of this study was thus to investigate the role of VEGF in the pathogenesis of MCD.
Methods:
The expression of the gene for VEGF and VEGF receptor-2 (VEGFR-2) was estimated using in situ hybridization in renal biopsy specimens taken from patients with nephrotic syndrome and diagnosed histologically as MCD. The results were compared with those obtained in normal renal tissue. Biopsy specimens from eight patients diagnosed as having MCD were randomly selected for the study. The patients were aged 4-60 years at the time of the biopsy. There were four females and four males. All patients had presented with a nephrotic syndrome, five with recent onset of the disease, two with repeated attacks of the syndrome and one had reduced renal function.
Results:
The gene expression for VEGF, measured as the proportional glomerular area occupied by autoradiographic grains, was significantly less in the patients with MCD than in controls (1.9 +/- 0.4 vs 4.8 +/- 0.6%, P < 0.0025), whereas the gene expression for VEGFR-2 was no different to controls (1.9 +/- 0.4 vs 2.0 +/- 0.2%).
Conclusions:
MCD is associated with a reduction in the expression of the gene for VEGF. As VEGF may play an important role in renal repair and survival, it is postulated that the deficiency, which we have shown, may lead to the dysregulation of the repair process in MCD.
Insights
Minimal change disease (MCD) is linked to reduced vascular endothelial growth factor (VEGF) gene expression. This deficiency may impair kidney repair processes in patients with nephrotic syndrome.
Area of Science:
- Nephrology
- Molecular Biology
- Pathogenesis of Kidney Diseases
Background:
- Minimal change disease (MCD) is a primary cause of nephrotic syndrome in children and adults.
- The exact cause of MCD is unknown, but a plasma permeability factor is suspected.
- Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is implicated.
Purpose of the Study:
- To investigate the role of VEGF in the pathogenesis of Minimal Change Disease.
- To assess VEGF and VEGF receptor-2 (VEGFR-2) gene expression in MCD renal biopsies.
Main Methods:
- In situ hybridization was used to estimate gene expression of VEGF and VEGFR-2 in renal biopsy specimens.
- MCD patient samples were compared with normal renal tissue.
- Eight MCD patients (4-60 years old, 4 male/4 female) with varying nephrotic syndrome presentations were studied.
Main Results:
- VEGF gene expression was significantly lower in MCD patients compared to controls (1.9% vs. 4.8%, P < 0.0025).
- VEGFR-2 gene expression showed no significant difference between MCD patients and controls (1.9% vs. 2.0%).
Conclusions:
- Minimal change disease is associated with reduced VEGF gene expression.
- The observed VEGF deficiency may lead to dysregulated repair processes in MCD.
- VEGF's role in renal repair and survival suggests its deficiency contributes to MCD pathogenesis.
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