Optimal cutoff point for immunoperoxidase detection of C4d in the renal allograft: results from a multicenter study.
Optimal cutoff point for immunoperoxidase detection of C4d in the renal allograft: results from a multicenter study.
复制标题
DOI：
10.1097/tp.0b013e3181f7fec9
复制
发表时间：
2010-11-27
期刊：
影响因子：
6.2
通讯作者：
Grande JP
中科院分区：
文献类型：
--
作者：
Crary GS;Raissian Y;Gaston RC;Gourishankar SM;Leduc RE;Mannon RB;Matas AJ;Grande JP
尽管管周毛细血管中的 C4d 沉积已被确定为随后肾同种异体移植物丢失的强烈危险因素，但在福尔马林固定石蜡包埋材料中建立阳性染色所需的管周毛细血管分数的最佳截止值尚未系统确定。本研究的目的是在比较局部和中心病理学的多中心研究中建立最能预测肾活检肾结果的阳性染色阈值。从 296 名患者身上获得未染色的肾活检切片。通过免疫过氧化物酶染色检测C4d染色阳性的管周毛细血管的百分比。 C4d 沉积百分比范围为 0% 至 90%，其中 44% (129/296) 具有 C4d 染色阳性百分比。阳性病例的中位数为 25%。定性报告当地 C4d+ 结果，其中 28% 记录为 C4d 阳性。使用中央确定的 10% 截止值，对局部和中央 C4d 染色的一致性进行测试是公平的（Kappa 0.40，95% CI 0.29-0.51）。将中央确定的截止值提高到 25% 或 50% 不会改变 Kappa 值（分别为 0.44 和 0.41）。根据 Cox 比例风险模型，使用 10% 截止值的 C4d 阳性（集中确定的评估）是移植物丢失时间的最强预测因子（HR 2.66，95% CI [1.68，4.21]）。集中确定的 C4d 阳性与指示急性炎症的班夫评分相关，但与指示纤维化/萎缩或移植肾小球病的评分无关。我们的研究结果表明，C4d 阳性（免疫过氧化物酶定义为 ≥10%）是移植物丢失的有力预测因子。
Although C4d deposition in peritubular capillaries has been identified as a strong risk factor for subsequent renal allograft loss, the optimal cut-off for the fraction of peritubular capillaries needed to establish a positive stain in formalin-fixed paraffin-embedded material has not been systematically defined. The objective of this study was to establish the threshold for positive staining that best predicts renal outcome in renal biopsies in a multicenter study in which local and central pathology were compared. Unstained renal biopsy slides were obtained from 296 patients. The percentage of peritubular capillaries staining positively for C4d was detected by immunoperoxidase staining. The percentage C4d deposition ranged from 0% to 90% with 44% (129/296) having a positive percentage of C4d staining. The median for positive cases was 25%. Local C4d+ results were reported qualitatively, with 28% recorded as positive for C4d. Using a centrally-determined cut-off of 10%, tests for agreement of local and central C4d staining were fair (Kappa 0.40, 95% CI 0.29-0.51). Raising the centrally-determined cut-off to 25% or 50% did not change the Kappa values (0.44 and 0.41, respectively). By Cox proportional hazards model, C4d positivity (centrally-determined assessment) using a cut-off of 10% was the strongest predictor of time to graft loss (HR 2.66, 95% CI [1.68, 4.21]). Centrally-determined C4d positivity correlated with Banff scores indicative of acute inflammation, but not with scores indicative of fibrosis/atrophy or transplant glomerulopathy. Our findings indicate that C4d positivity, defined as ≥10% by immunoperoxidase, is a strong predictor of graft loss.