Vascular endothelial growth factor gene expression is correlated with glomerular neovascularization in human diabetic nephropathy

Abstract

In diabetic nephropathy (DN) small vessels are frequently observed around the glomerular vascular pole in addition to normal afferent and efferent arterioles; this is regarded as neovascularization . Because vascular endothelial growth factor (VEGF) promotes vascular generation, the authors investigated the relationship between glomerular VEGF gene expression and structural glomerular changes in the early stage of human DN. Kidney specimens were obtained from 18 type 2 DN patients by open renal biopsy. Additional vessels were distinguished by light microscopy as either afferent or efferent arterioles. Glomerular VEGF messenger RNA expression was determined by using in situ hybridization. The mesangial matrix area was quantified, and the ratio of the mesangial matrix area to the whole glomerular area was calculated to determine the mesangial matrix index (MMI). There were significantly more glomeruli with extra vessels in DN than in normal kidneys. The degree of neovascularization was significantly increased in DN and correlated with the magnitude of VEGF messenger RNA expression (r 2 = 0.46, P = 0.010) and MMI (r 2 = 0.45, P = 0.0093). These findings suggest that glomerular VEGF may be involved in structural changes in human DN at an early stage.