Increased angiotensin-converting enzyme and type 1 angiotensin receptors in cortical vasculature and tubulointerstitium of chronically rejected human kidney allografts

• Published in: Nephrology (Carlton, Vic.) Vol. 6; no. 5; pp. 223 - 232
• Main Authors: Ohishi, Mitsuru, Ueda, Makiko, Tanabe, Shigeru, Han, Young-Sin, Mendelsohn, Frederick Ao, Zhuo, Jia L
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Science Pty 01.10.2001
• Subjects: angiotensin II; angiotensin-converting enzyme; autoradiography; immunohistochemistry; renal allograft rejection; transplantation
• ISSN: 1320-5358; 1440-1797
• DOI: 10.1046/j.1440-1797.2001.00045.x

Chronic rejection of human renal allografts after transplantation is characterized by interstitial infiltration, arteriosclerosis and glomerulosclerosis in the grafts. Apart from tissue HLA compatibility, angiotensin II (AII) may be implicated in accelerating the processes of chronic rejection. In the present study, the cellular distribution of angiotensin‐converting enzyme (ACE) and type 1 AII (AT1) receptors was mapped and compared in non‐rejected human kidneys (n = 8) and chronically rejected renal allografts (n = 9) using complementary immunohistochemistry and quantitative in vitro autoradiography. Chronically rejected allografts showed typical histopathological characteristics of tissue rejection, including concentric intimal thickening of intrarenal arteries, extensive or focal glomerulosclerosis, tubular atrophy and severe tubulointerstitial fibrosis. In rejected allografts, total ACE binding in the cortex was decreased to 46% of that in non‐rejected kidneys (P < 0.01), whereas AT1 receptor binding in the glomeruli and the inner stripe of the outer medulla was maintained. However, ACE and AT1 receptor binding were increased in the cortical tubulointerstitium of chronically rejected allografts. In non‐rejected kidneys, strong ACE immunostaining occurred in proximal tubules and vascular endothelium, whereas AT1 receptors occurred in vascular smooth muscle cells, as expected. In rejected allografts, intense ACE and AT1 receptor immunostaining were detected not only in the same sites as those non‐rejected kidneys, but also in cortical tubulointerstitium between atrophied tubules and surrounding the glomeruli. AT1 receptors were markedly up‐regulated in vascular smooth muscle cells of thickened atherosclerotic vessels. These results provide novel morphological evidence that increased expression and/or altered distribution of ACE and AT1 receptors in cortical tubulointerstitium and in the neointima of intrarenal arteries may play an important role in the progression of chronic rejection of human renal allografts after transplantation.