静脉注射免疫球蛋白与标准治疗方案治疗肾移植受者慢性活动性抗体介导排斥反应的随机对照试验。

A randomized controlled trial of intravenous immunoglobulin vs standard of care for the treatment of chronic active antibody-mediated rejection in kidney transplant recipients.

作者信息

Mulley William R, Tharmaraj Dhakshayini, Polkinghorne Kevan R, Tesch Greg H, Dayan Sukhpal K, Kwan Edward, Olshansky Moshe, Mark Tia, Lee Darren, Mount Peter F, Wong Germaine, Wyburn Kate R, Lim Wai H, Kerr Peter G, Nikolic-Paterson David J, Kanellis John

机构信息

Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia; Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia.

出版信息

Kidney Int. 2025 Sep;108(3):470-480. doi: 10.1016/j.kint.2025.04.023. Epub 2025 May 22.

DOI:10.1016/j.kint.2025.04.023

PMID:40412552

Abstract

INTRODUCTION

Chronic active antibody-mediated rejection (AMR) is the leading cause of death-censored kidney allograft loss, with no proven treatments. While intravenous immunoglobulin (IVIG) has been used in certain cases, its efficacy is unknown.

METHODS

In this open-label multicenter randomized controlled trial (VIPAR), participants with biopsy-proven chronic active AMR, were assigned to six doses (1 g/kg/month) of IVIG or no-IVIG. The primary end point was the difference in slopes of the chronic allograft damage index (CADI) scores between groups, across four allograft biopsies (baseline, three, six and 12 months). Secondary outcomes, assessed at baseline, three, six and 12 months, included change in estimated glomerular filtration rate (eGFR), change in donor-specific anti-HLA antibodies (DSA), allograft and patient survival, and change in intra-graft mRNA expression.

RESULTS

Fifteen participants were randomized to each arm. Their median age was 54.3 years, 22 were male and mean eGFR was 43.3 ml/min/1.73m. Participants in the no-IVIg group experienced a significant increase in mean CADI (+0.28/month, 95% confidence interval 0.14 to 0.41), while the IVIG group did not (-0.004/month, -0.13 to 0.12). Over two years, eGFR significantly declined more rapidly in the no-IVIG group (-1.1 ml/min/month, -1.5 to -0.7 ml/min/month) than the IVIG group (-0.4 ml/min/month, -0.8 to 0.03 ml/min/month). Differences in patient and allograft survival were not evident by 12 months. Intra-graft expression of 59 genes (mostly B-cell related) reduced with IVIG relative to no-IVIG.

CONCLUSIONS

IVIG therapy was associated with stabilization in allograft histology and eGFR in kidney transplant recipients with chronic active AMR.

TRIAL REGISTRATION

Registered at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=347495 with study number ACTRN12612000252819.

摘要

引言

慢性活动性抗体介导的排斥反应（AMR）是肾移植受者死亡审查后移植肾丢失的主要原因，目前尚无经证实有效的治疗方法。虽然静脉注射免疫球蛋白（IVIG）已在某些病例中使用，但其疗效尚不清楚。

方法

在这项开放标签的多中心随机对照试验（VIPAR）中，经活检证实为慢性活动性AMR的参与者被分配接受六剂（1 g/kg/月）IVIG或不接受IVIG治疗。主要终点是在四次移植肾活检（基线、三个月、六个月和十二个月）期间，两组间慢性移植肾损伤指数（CADI）评分斜率的差异。在基线、三个月、六个月和十二个月时评估的次要结局包括估计肾小球滤过率（eGFR）的变化、供体特异性抗HLA抗体（DSA）的变化、移植肾和患者的生存率以及移植肾内mRNA表达的变化。

结果

每组随机分配15名参与者。他们的中位年龄为54.3岁，22人为男性，平均eGFR为43.3 ml/min/1.73m²。未接受IVIG治疗的组平均CADI显著增加（+0.28/月，95%置信区间0.14至0.41），而IVIG组则未增加（-0.004/月，-0.13至0.12）。在两年时间里，未接受IVIG治疗的组eGFR下降速度明显快于IVIG组（-1.1 ml/min/月，-1.5至-0.7 ml/min/月）（IVIG组为-0.4 ml/min/月，-0.8至0.03 ml/min/月）。到12个月时，患者和移植肾生存率的差异不明显。与未接受IVIG治疗相比，接受IVIG治疗后移植肾内59个基因（大多与B细胞相关）的表达降低。