Ishii Yasuo, Sawada Tokihiko, Kubota Keiichi, Fuchinoue Syouhei, Teraoka Satoshi, Shimizu Akira
Department of Surgery, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Kidney Int. 2005 Jan;67(1):321-32. doi: 10.1111/j.1523-1755.2005.00085.x.
Chronic allograft nephropathy (CAN) remains the most important cause of late renal graft loss. However, the mechanism for graft dysfunction and the process of the development of CAN are not well understood. This study examined the role of microvascular injury in the development of CAN.
We studied renal biopsies obtained from grafts with CAN (N= 79) and pretransplant control kidneys (N= 20). Microvascular injury was examined morphologically, and was correlated with interstitial fibrosis, glomerular sclerosis, graft function, and the severity of CAN. The humoral and cellular immunity involved in CAN were examined by C4d, CD3, and TIA-1 staining.
In all the cases of CAN, microvascular injury was evident with or without CD3-positive T cells, TIA-1-positive cytotoxic cells, and/or C4d+ complement deposition. Irrespective of chronic rejection (N= 14), C4d+ chronic humoral rejection (N= 6), or other CAN, the development process of CAN was characterized by injury and progressive loss of identifiable peritubular capillaries (PTCs) accompanied with the development of interstitial fibrosis. Injured PTCs were characterized morphologically by the process of angioregression with the presence of apoptotic cells, lamination of the basement membrane, and loss of PTCs. The low number of PTCs correlated significantly with the severity of CAN (r=-0.74, P < 0.001), the development of interstitial fibrosis (r=-0.75, P < 0.001), graft dysfunction (r=-0.69, P < 0.001), and also correlated weakly with proteinuria (r=-0.45, P < 0.05). In the glomeruli, capillary loss significantly correlated with the degree of glomerular sclerosis (r=-0.66, P < 0.001) and proteinuria (r=-0.65, P < 0.001), but did not correlate with the severity of CAN (r=-0.24, P > 0.05) or graft dysfunction (r=-0.32, P > 0.05).
CAN was characterized by progressive injury to the renal microvasculature and the development of renal scarring. In particular, injury, angioregression and progressive loss of the PTC network strongly contributed to the development of interstitial fibrosis and graft dysfunction in CAN, and might play a crucial role in the development of CAN.
慢性移植肾肾病（CAN）仍然是肾移植后期丢失的最重要原因。然而，移植肾功能障碍的机制以及CAN的发展过程尚未完全明确。本研究探讨了微血管损伤在CAN发展中的作用。
我们研究了取自CAN移植肾（N = 79）和移植前对照肾（N = 20）的肾活检组织。对微血管损伤进行形态学检查，并将其与间质纤维化、肾小球硬化、移植肾功能以及CAN的严重程度相关联。通过C4d、CD3和TIA-1染色检测CAN中涉及的体液免疫和细胞免疫。
在所有CAN病例中，无论有无CD3阳性T细胞、TIA-1阳性细胞毒性细胞和/或C4d +补体沉积，微血管损伤均很明显。无论慢性排斥反应（N = 14）、C4d +慢性体液排斥反应（N = 6）或其他CAN情况如何，CAN的发展过程均以可识别的肾小管周围毛细血管（PTC）损伤和逐渐丧失为特征，并伴有间质纤维化的发展。受损的PTC在形态学上的特征是血管消退过程，伴有凋亡细胞、基底膜分层以及PTC丧失。PTC数量少与CAN的严重程度（r = -0.74，P < 0.001）、间质纤维化的发展（r = -0.75，P < 0.001）、移植肾功能障碍（r = -0.69，P < 0.001）显著相关，与蛋白尿也有较弱的相关性（r = -0.45，P < 0.05）。在肾小球中，毛细血管丧失与肾小球硬化程度（r = -0.66，P < 0.001）和蛋白尿（r = -0.65，P < 0.001）显著相关，但与CAN的严重程度（r = -0.24，P > 0.05）或移植肾功能障碍（r = -0.32，P > 0.05）无关。
CAN的特征是肾微血管的进行性损伤和肾瘢痕形成。特别是，PTC网络的损伤、血管消退和逐渐丧失在CAN的间质纤维化和移植肾功能障碍发展中起重要作用，可能在CAN的发展中起关键作用。
