Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI.
Transplantation. 2019 Jul;103(7):1468-1476. doi: 10.1097/TP.0000000000002487.
Limited information exists about outcomes of HLA donor-specific antibody (DSA) negative (DSA-) microvascular inflammation (MVI).
We report our experience with 25 DSA- patients with MVI compared to 155 DSA+ patients who met Banff 2013 criteria for antibody-mediated rejection (AMR). We also compared outcomes to 228 DSA+ patients whose biopsies were negative for rejection and served as a negative control.
There were no significant differences in the baseline characteristics between the DSA- MVI and DSA+ AMR groups. At the time of diagnosis, both groups had similar graft function. The DSA- group had higher MVI scores but lower C4d scores. At last follow-up, renal function was similar between the groups. There were 12 (48%) graft failures in the DSA- group and 59 (38%) graft failures in the DSA+ group, which was not statistically different. Similar results were found after matching for the MVI scores, C4d, and treatment between 2 groups. We also found similar outcomes between DSA- and DSA+ patients when only including those who would have met Banff 2017 criteria for AMR. In univariate Cox regression analyses, estimated glomerular filtration rate at time of biopsy, glomerulitis, rituximab, diabetes, v score, allograft glomerulopathy, fibrous intimal thickening, tubular atrophy, and interstitial fibrosis scores were associated with graft failure. In multivariate analysis, only estimated glomerular filtration rate was protective. Both groups had significantly worse outcomes than the DSA+-negative controls without AMR.
Our findings suggest that outcomes and response to treatment with HLA DSA- MVI patients are similarly poor to those with DSA+ MVI patients, supporting a critical role for MVI in the diagnosis of AMR.
关于 HLA 供体特异性抗体(DSA)阴性(DSA-)微血管炎症(MVI)的结果,目前信息有限。
我们报告了 25 例 DSA- MVI 患者的经验,与 155 例符合 Banff 2013 年抗体介导排斥反应(AMR)标准的 DSA+患者进行了比较。我们还将结果与 228 例活检无排斥反应的 DSA+患者进行了比较,作为阴性对照。
DSA-MVI 和 DSA+ AMR 组之间的基线特征无显著差异。在诊断时,两组的移植物功能相似。DSA-组的 MVI 评分较高,但 C4d 评分较低。在最后一次随访时,两组的肾功能相似。DSA-组有 12 例(48%)移植物失功,DSA+组有 59 例(38%)移植物失功,差异无统计学意义。在两组之间匹配 MVI 评分、C4d 和治疗后,也得到了类似的结果。我们还发现,当仅包括那些符合 Banff 2017 年 AMR 标准的患者时,DSA-和 DSA+患者的结果相似。在单变量 Cox 回归分析中,活检时估计肾小球滤过率、肾小球炎、利妥昔单抗、糖尿病、v 评分、同种异体移植肾小球病、纤维内膜增厚、肾小管萎缩和间质纤维化评分与移植物失功相关。在多变量分析中,只有估计肾小球滤过率具有保护作用。与无 AMR 的 DSA+-阴性对照组相比,两组的预后均显著较差。
我们的研究结果表明,DSA- MVI 患者的预后和治疗反应与 DSA+ MVI 患者相似,这支持 MVI 在 AMR 诊断中的关键作用。