Peritubular capillary loss is associated with chronic tubulointerstitial injury in human kidney: Altered expression of vascular endothelial growth factor
Endothelial Growth Factors
Chronic tubulointerstitial injury (CTI) including tubular atrophy and interstitial fibrosis represents one major determinant for the progression of chronic renal disease regardless of cause. Although peritubular capillaries (PTCs) are essential to maintain the normal structure and function of renal tubules, little is known about the role of PTCs in the development of CTI. The integrity of PTCs seems to be regulated by growth factors. Vascular endothelial cell growth factor (VEGF) has recently been recognized as a potent regulator of angiogenesis, vascular survival, and vascular permeability. Knowledge of the role of VEGF in renal disease is still rudimentary, and its role in CTI has not been explored. We analyzed the morphologic changes of PTCs and correlated them with other morphologic parameters of CTI in 32 human kidneys with various types of chronic tubulointerstitial disease. The VEGF expression was immunohistochemically evaluated. Compared with normal kidney, PTC loss (41% to 55% of control) and reduced size of PTCs (55% to 88% of control) were noted in kidneys with CTI. The PTC density was positively correlated with the proximal tubular density (r = 0.66, P <.0001), proximal tubular size (r = 0.54, P <.001), and negatively correlated with interstitial volume (r = -0.84, P <.0001). Compared with normal kidney, where podocytes were the only cell type that constantly expressed VEGF, an interesting pattern of increased VEGF expression by renal tubules, especially morphologically intact or hypertrophic ones, was shared by all cases with CTI. Loss of VEGF in sclerotic glomeruli was noted. PTC injury is pathogenetically linked to tubular atrophy, tubular loss, and interstitial fibrosis in human kidneys with CTI and might be a key factor for the progression of chronic tubulointerstitial disease. The characteristic and uniform pattern of altered VEGF expression in kidneys with CTI may result from ischemia induced by PTC loss and represent a protective mechanism against further PTC injuries. HUM PATHOL 31:1491-1497.