Fujita Emiko, Nagahama Kiyotaka, Shimizu Akira, Aoki Michiko, Higo Seiichiro, Yasuda Fumihiko, Mii Akiko, Fukui Megumi, Kaneko Tomohiro, Tsuruoka Shuichi
Department of Nephrology, Nippon Medical School.
J Nippon Med Sch. 2015;82(1):27-35. doi: 10.1272/jnms.82.27.
The associations of glomerular capillary and endothelial injury with the formation of necrotizing and crescentic lesions in cases of crescentic glomerulonephritis (GN) have not been evaluated in detail.
Glomerular capillary and endothelial cell injury were assessed in renal biopsy specimens of crescentic GN, including those from patients with anti-neutrophil cytoplasmic autoantibodies (ANCA) -associated GN (n=45), anti-glomerular basement membrane (GBM) GN (n=7), lupus GN (n=21), and purpura GN (n=45) with light and electron microscopy and immunostaining for CD34.
In ANCA-associated GN, anti-GBM GN, lupus GN, and purpura GN, almost all active necrotizing glomerular lesions began as a loss of individual CD34-positive endothelial cells in glomerular capillaries, with or without leukocyte infiltration. Subsequently, necrotizing lesions developed and were characterized by an expansive loss of CD34-positive cells with fibrin exudation, GBM rupture, and cellular crescent formation. With electron microscopy, capillary destruction with fibrin exudation were evident in necrotizing and cellular crescentic lesions. During the progression to the chronic stage of crescentic GN, glomerular sclerosis developed with the disappearance of both CD34-positive glomerular capillaries and fibrocellular-to-fibrous crescents. In addition, the remaining glomerular lobes without crescents had marked collapsing tufts, a loss of endothelial cells, and the development of glomerular sclerosis.
The loss of glomerular capillaries with endothelial cell injury is commonly associated with the formation of necrotizing and cellular crescentic lesions, regardless of the pathogeneses associated with different types of crescentic GN, such as pauci-immune type ANCA-associated GN, anti-GBM GN, and immune-complex type GN. In addition, impaired capillary regeneration and a loss of endothelial cells contribute to the development of glomerular sclerosis with fibrous crescents and glomerular collapse.
新月体性肾小球肾炎（GN）中，肾小球毛细血管和内皮损伤与坏死性及新月体病变形成之间的关联尚未得到详细评估。
采用光镜、电镜及CD34免疫染色，对新月体性GN肾活检标本进行评估，包括抗中性粒细胞胞浆自身抗体（ANCA）相关性GN患者（n = 45）、抗肾小球基底膜（GBM）GN患者（n = 7）、狼疮性GN患者（n = 21）及紫癜性GN患者（n = 45）的标本。
在ANCA相关性GN、抗GBM GN、狼疮性GN和紫癜性GN中，几乎所有活动性坏死性肾小球病变均始于肾小球毛细血管中单个CD34阳性内皮细胞的丢失，伴或不伴有白细胞浸润。随后，坏死性病变发展，其特征为CD34阳性细胞广泛丢失，伴有纤维蛋白渗出、GBM破裂及细胞性新月体形成。电镜下，坏死性和细胞性新月体病变中可见毛细血管破坏伴纤维蛋白渗出。在新月体性GN进展至慢性期的过程中，随着CD34阳性肾小球毛细血管及纤维细胞性至纤维性新月体的消失，出现了肾小球硬化。此外，未形成新月体的剩余肾小球小叶有明显的肾小球毛细血管襻塌陷、内皮细胞丢失及肾小球硬化的发展。
无论与不同类型新月体性GN相关的发病机制如何，如寡免疫型ANCA相关性GN、抗GBM GN及免疫复合物型GN，肾小球毛细血管伴内皮细胞损伤的丢失通常与坏死性及细胞性新月体病变的形成有关。此外，毛细血管再生受损及内皮细胞丢失促成了伴有纤维性新月体和肾小球塌陷的肾小球硬化的发展。
