Decreased urinary excretion of vascular endothelial growth factor in idiopathic membranous glomerulonephritis

Background. Membranous glomerulonephritis (MGN) has, for unknown reasons, a n unpredictable and highly variable clinical course. Vascular endothelial g rowth factor (VEGF) enhances endothelial cell proliferation, angiogenesis, microvascular permeability, and monocyte chemotaxis, and it activates prote inases. In normal kidneys, it is predominantly expressed by glomerular podo cytes, where its physiological function and role in development of renal di seases are obscure. This study was designed to evaluate the urinary excreti on of VEGF in MGN compared with several other glomerular disease and to ass es its relationships to the clinical activity of MGN. Methods. Urinary VEGF was studied during renal biopsy using a sandwich enzy me immunoassay from 30 patients with idiopathic MGN, 8 with minimal change glomerulonephritis, 10 with focal segmental gromerulosclerosis (FSGS), 8 wi th necrotizing glomerulonephritis associated with systemic vasculitis, and 12 with diabetic nephropathy. In addition, 33 healthy controls were examine d. Fifteen patients with MGN were re-evaluated 12 months later, and the evo lution of proteinuria was compared with changes in urinary VEGF excretion. Results. Tn healthy control subjects, urinary VEGF excretion was 68 +/- 10 (95% CI, 49 to 88) ng/mmol creatinine (U-Cr). In MGN, the excretion was dec reased to 16 +/- 3 (CI, 10 to 23) ng/mmol crea (P < 0.0001, ANOVA), whereas in minimal change glomerulonephritis and diabetic nephropathy, it was unch anged [55 +/- 14 (CI, 24 to 86) and 101 +/- 25 (CI, 45 to 156) ng/mmol U-Cr , respectively, P = NS]. In vasculitis and FSGS patients, the excretion was higher than normal [184 +/- 68 (CI, 24 to 344), P = 0.01, and 160 +/- 29 ( CI 95 to 226), P = 0.002 ng/mmol U-Cr, respectively]. The excretion did not correlate with serum VEGF, renal function, or proteinuria. In the follow-u p of 15 patients, improving MGN (decreasing proteinuria) was associated wit h increasing VEGF excretion, while persistent disease (no change or increas e of proteinuria) was associated with constantly low urinary VEGF excretion . The change in urinary protein excretion over one year correlated inversel y with the change in urinary VEGF (r = -0.57, P = 0.026). Conclusions. MGN is associated with decreased urinary VEGF compared with no rmal subjects, which is in contrast with other proteinuric diseases. Moreov er, decreasing clinical activity (proteinuria) is accompanied by increasing VEGF excretion. Urinary VEGF may serve as an indicator of activity of MGN.