TY - JOUR
T1 - Peritubular capillary loss is associated with chronic tubulointerstitial injury in human kidney
T2 - Altered expression of vascular endothelial growth factor
AU - Choi, Yeong Jin
AU - Chakraborty, Subenduu
AU - Nguyen, Vinh
AU - Nguyen, Charlie
AU - Kim, Byung Kee
AU - Shim, Sang In
AU - Suki, Wadi N.
AU - Truong, Luan
N1 - Funding Information:
From the Renal Pathology Laboratory, Departments of Pathology and Medicine, The Methodist Hospital and Baylor College of Medicine, Houston, TX; and the Department of Clinical Pathology, The Catholic University of Korea, Seoul, Korea. Accepted for publication September 12, 2000. Supported in part by the Moran Foundation. Presented as an abstract form at the 1999 Meeting of the American Society of Nephrology in Miami, FL. Address correspondence and reprint requests to Luan D. Truong, MD, Department of Pathology, M.S. 205, The Methodist Hospital, 6565 Fannin St, Houston, TX 77030. Copyright © 2000 by W.B. Saunders Company 0046-8177/00/3112-0007$10.00/0 doi:10.1053/hupa.2000.20373
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Chronic tubulointerstitial injury
KW - Interstitial fibrosis
KW - Tubular atrophy
KW - Tubular loss
KW - Vascular endothelial growth factor
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U2 - 10.1053/hupa.2000.20373
DO - 10.1053/hupa.2000.20373
M3 - Article
C2 - 11150374
AN - SCOPUS:0034523928
VL - 31
SP - 1491
EP - 1497
JO - Human Pathology
JF - Human Pathology
SN - 0046-8177
IS - 12
ER -