Early Ultrastructural Changes in Renal Allografts: Correlation With Antibody-Mediated Rejection and Transplant Glomerulopathy

Early Ultrastructural Changes in Renal Allografts: Correlation With Antibody-Mediated Rejection and Transplant Glomerulopathy
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DOI:
10.1111/j.1600-6143.2011.03647.x
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发表时间:
2011-10-01
影响因子:
8.8
通讯作者:
Mirocha, J.
Mirocha, J.
中科院分区:
医学2区
文献类型:
--
作者:
Haas, M.;Mirocha, J.

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移植肾小球病(TG)与抗体介导的肾移植排斥反应(AMR)和移植物存活率降低有关。组织学上,TG通常见于移植后>1年。然而,超微结构的变化,包括肾小球内皮细胞肿胀,内皮下增宽和早期肾小球基底膜复制与TG的发展,但出现更早。我们研究了AMR的这些变化的特异性,以及这些变化是否与TG的发展不可避免地相关。在98例移植后3个月内进行的有血清学数据的原因肾移植活检中,17例显示C4d阳性AMR,16例有AMR和供体特异性抗体(DSA)的组织学变化,但无C4d。在17例C4d阳性AMR的活检中,11例可见所有三种超微结构变化,16例有AMR和DSA组织学变化但无C4d的活检中,8例可见所有三种超微结构变化,65例无AMR和/或DSA组织学变化的活检中,0例可见所有三种超微结构变化(前两组与后一组相比,p < 0.0001)。20例DSA阳性患者(18例AMR组织学改变,11例C4d阳性)进行了≥ 1次随访活检; 8例在移植后3.5-30个月发生明显的TG。在18例DSA和AMR组织学改变的患者中,11例C4d阳性和7例C4d阴性,早期活检后AMR治疗显著降低了随后明显TG的发展。
Transplant glomerulopathy (TG) is associated with antibody-mediated renal allograft rejection (AMR) and reduced graft survival. Histologically, TG is typically seen >1 year posttransplantation. However, ultrastructural changes including glomerular endothelial swelling, subendothelial widening and early glomerular basement membrane duplication are associated with development of TG but appear much earlier. We examined the specificity of these changes for AMR, and whether these are inevitably associated with development of TG. Of 98 for cause renal allograft biopsies carried out within 3 months of transplantation with available serologic data, 17 showed C4d-positive AMR and 16 had histologic changes of AMR and donor-specific antibodies (DSA), but no C4d. All three ultrastructural changes were seen in 11 of 17 biopsies with C4d-positive AMR, 8 of 16 with histologic changes of AMR and DSA but no C4d, and 0 of 65 without histologic changes of AMR and/or DSA (p < 0.0001 for both of the former groups vs. the latter). Twenty patients with positive DSA (18 with histologic changes of AMR and 11 C4d-positive) had >= 1 follow-up biopsy; eight developed overt TG 3.5-30 months posttransplantation. Among the 18 patients with DSA and histologic changes of AMR, 11 C4d-positive and 7 C4d-negative, treatment for AMR after the early biopsy significantly reduced subsequent development of overt TG.