Background: Membranous glomerulonephritis (MGN) has a variable clinical course, and factors that determine the prognosis are unknown. Our previous study suggested that urinary excretion of vascular endothelial growth factor (VEGF) is decreased in active MGN, but normalizes in remission. In the present study, VEGF protein and messenger RNA (mRNA) expression were investigated in this disease.
Methods: Twelve patients with clinically active and/or progressive MGN were studied by using urinary assays for VEGF and soluble VEGF receptor-1 (sVEGF-R1), semiquantitative scoring of serial renal biopsy specimens by using immunohistochemical staining for VEGF protein, and in situ hybridization for VEGF mRNA. Results were compared with healthy controls and normal parts of nephrectomized kidneys.
Results: Urinary VEGF excretion was decreased significantly (P < 0.001 versus controls) in MGN, but there was no difference in sVEGF-R1 excretion compared with healthy subjects. VEGF protein expression was diminished significantly in glomerular podocytes (P = 0.008), as well as in extraglomerular small arteries (P = 0.03) and arterioles (P = 0.008) in MGN. Total kidney VEGF score (the sum of scores of individual kidney compartments) also was decreased in MGN (P < 0.05) and remained low in repeated biopsies. Expression of VEGF mRNA localized predominantly to podocytes in normal kidneys was greatly reduced in MGN.
Conclusion: Clinically active MGN is associated with diminished expression of VEGF protein and mRNA, mainly in podocytes, and expression remains depressed in persistently active and/or progressive disease. This is reflected by decreased urinary VEGF excretion. These findings point to potentially reversible podocyte injury and, together with our previous study, suggest that VEGF may have a protective role during the evolution of MGN.