Nickeleit V, Vamvakas E C, Pascual M, Poletti B J, Colvin R B
Department of Pathology, Massachusetts General Hospital, Boston 02114, USA.
J Am Soc Nephrol. 1998 Jul;9(7):1301-8. doi: 10.1681/ASN.V971301.
Diagnosis of allograft dysfunction relies on the assessment of arterial lesions. This study was designed to evaluate the prognostic significance of common specific vascular lesions in acute allograft rejection. Renal allograft biopsies (n = 111) with acute cellular rejection were scored for endarteritis, mononuclear cell adherence to endothelial cells, endothelial activation, fibrinoid necrosis, foam cells, and intimal fibrosis. These vascular lesions and other classic histologic features were correlated with outcome. Rejection with endarteritis (found in 54% of biopsies) was less responsive to steroid treatment than rejection without endarteritis, as judged by recovery of creatinine in 3 wk (P = 0.03). Larger numbers of sampled arteries improved the predictive accuracy. Sticking of mononuclear cells to endothelial cells also correlated with steroid resistance (P < 0.05). Rejection with or without endarteritis responded to OKT3/antithymocyte globulin treatment equally well (61% versus 65%, respectively). Rejection with fibrinoid arterial necrosis (4% of biopsies) did not respond to either steroids or antibodies (0%). One-year graft failure was 21% without endarteritis, 28% with endarteritis, and 100% with fibrinoid necrosis. Activated endothelial cells and interstitial hemorrhage were associated with endarteritis and graft failure (all P < 0.05). None of the other scored features had any statistically significant correlation with outcome. Thus, specific arterial lesions (endarteritis, fibrinoid necrosis, activated endothelial cells, mononuclear cell margination) and interstitial hemorrhage, but not the extent of the interstitial infiltrate or tubulitis, are correlated with response to antirejection therapy and/or 1-yr clinical outcome. Grading systems for therapeutic trials and clinical management should emphasize scoring of specific vascular lesions.
同种异体移植功能障碍的诊断依赖于对动脉病变的评估。本研究旨在评估急性同种异体移植排斥反应中常见特定血管病变的预后意义。对111例发生急性细胞排斥反应的肾移植活检标本进行动脉内膜炎、单核细胞黏附于内皮细胞、内皮细胞活化、纤维蛋白样坏死、泡沫细胞和内膜纤维化评分。将这些血管病变及其他经典组织学特征与预后相关联。从3周时肌酐的恢复情况判断，伴有动脉内膜炎的排斥反应（在54%的活检标本中发现）对类固醇治疗的反应不如无动脉内膜炎的排斥反应（P = 0.03）。更多数量的采样动脉可提高预测准确性。单核细胞黏附于内皮细胞也与类固醇抵抗相关（P < 0.05）。伴有或不伴有动脉内膜炎的排斥反应对OKT3/抗胸腺细胞球蛋白治疗的反应同样良好（分别为61%和65%）。伴有纤维蛋白样动脉坏死的排斥反应（占活检标本的4%）对类固醇或抗体均无反应（0%）。无动脉内膜炎时1年移植失败率为21%，有动脉内膜炎时为28%，有纤维蛋白样坏死时为100%。活化的内皮细胞和间质出血与动脉内膜炎及移植失败相关（均P < 0.05）。其他评分特征与预后均无统计学显著相关性。因此，特定的动脉病变（动脉内膜炎、纤维蛋白样坏死、活化的内皮细胞、单核细胞靠边）和间质出血，而非间质浸润或肾小管炎的程度，与抗排斥治疗反应和/或1年临床预后相关。治疗试验和临床管理的分级系统应强调对特定血管病变的评分。
