Nankivell Brian J, Borrows Richard J, Fung Caroline L-S, O'Connell Philip J, Allen Richard D M, Chapman Jeremy R
Department of Renal Medicine, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia.
Transplantation. 2004 Jul 27;78(2):242-9. doi: 10.1097/01.tp.0000128167.60172.cc.
Subclinical rejection (SCR) is defined as histologically proven acute rejection in the absence of immediate functional deterioration.
We evaluated the impact of SCR in 961 prospective protocol kidney biopsies from diabetic recipients of a kidney-pancreas transplant (n=119) and one kidney transplant alone taken regularly up to 10 years after transplantation.
SCR was present in 60.8%, 45.7%, 25.8%, and 17.7% of biopsies at 1, 3, 12, and greater than 12 months after transplantation. Banff scores for acute interstitial inflammation and tubulitis declined exponentially with time. SCR was predicted by prior acute cellular rejection and type of immunosuppressive therapy (P<0.05-0.001). Tacrolimus reduced interstitial infiltration (P<0.001), whereas mycophenolate reduced tubulitis (P<0.05), and the combination effectively eliminated SCR (P<0.001). Persistent SCR of less than 2 years duration on sequential biopsies occurred in 29.2% of patients and was associated with prior acute interstitial rejection (P<0.001) and requirement for antilymphocyte therapy (P<0.05). It resolved by 0.49 +/- 0.33 years and resulted in higher grades of chronic allograft nephropathy (CAN, P<0.05). True chronic rejection, defined as persistent SCR of 2 years or more duration and implying continuous immunologic activation was found in only 5.8% of patients. The presence of SCR increased chronic interstitial fibrosis, tubular atrophy, and CAN scores on subsequent biopsies (P<0.05-0.001). SCR preceded and was correlated with CAN (P<0.001) on sequential analysis.
Histologic evidence of acute rejection in the absence of clinical suspicion resulted in significant tubulointerstitial damage to transplanted kidneys and contributed to CAN.
亚临床排斥反应（SCR）定义为在无即刻功能恶化情况下经组织学证实的急性排斥反应。
我们评估了SCR对961例接受肾 - 胰腺移植的糖尿病受者（n = 119）和1例单独肾移植受者前瞻性方案肾活检的影响，这些活检在移植后长达10年定期进行。
移植后1、3、12个月及超过12个月时，活检中SCR的发生率分别为60.8%、45.7%、25.8%和17.7%。急性间质炎症和肾小管炎的班夫评分随时间呈指数下降。SCR可通过既往急性细胞排斥反应和免疫抑制治疗类型预测（P < 0.05 - 0.001）。他克莫司减少间质浸润（P < 0.001），而霉酚酸减少肾小管炎（P < 0.05），两者联合可有效消除SCR（P < 0.001）。29.2%的患者在连续活检中出现持续时间小于2年的持续性SCR，这与既往急性间质排斥反应（P < 0.001）和抗淋巴细胞治疗需求（P < 0.05）相关。其在0.49±0.33年时缓解，并导致更高等级的慢性移植肾肾病（CAN，P < 0.05）。真正的慢性排斥反应定义为持续时间达2年或更长时间的持续性SCR，意味着持续的免疫激活，仅在5.8%的患者中发现。SCR的存在增加了后续活检时慢性间质纤维化、肾小管萎缩和CAN评分（P < 0.05 - 0.001）。在连续分析中，SCR先于CAN出现且与之相关（P < 0.001）。
在无临床怀疑情况下的急性排斥反应组织学证据导致移植肾显著的肾小管间质损伤，并促成CAN。
