与标准方案相比，硼替佐米和/或利妥昔单抗治疗肾移植抗体介导排斥反应：斯洛文尼亚国家中心的经验

Treatment of antibody-mediated rejection of kidney grafts with bortezomib and/or rituximab compared to standard regimen: experience of Slovene National Center.

作者信息

Oblak Teja, Lindič Jelka, Gubenšek Jakob, Kveder Radoslav, Aleš Rigler Andreja, Škoberne Andrej, Večerić Haler Željka, Borštnar Špela, Avguštin Nuša, Ponikvar Rafael, Mlinšek Gregor, Ferluga Dušan, Kojc Nika, Godnov Uroš, Kovač Damjan

出版信息

Clin Nephrol. 2017;88(13):91-96. doi: 10.5414/CNP88FX21.

DOI:10.5414/CNP88FX21

PMID:28664838

Abstract

BACKGROUND

The aim of our study was to determine outcomes of standard treatment of antibody-mediated rejection (ABMR) of kidney grafts as compared to the addition of bortezomib or rituximab.

METHODS

The cohort of this retrospective study included patients treated for ABMR of kidney grafts at our national center in the period of 2005 - 2017, divided into two groups: standard (ST) group treated standardly with plasmapheresis or immunoadsorption, intravenous immunoglobulins, and corticosteroids, and BR group treated with the addition of bortezomib and/or rituximab. Patient and graft survival at 2 years was analyzed by Kaplan-Meier method, and predictors of graft survival were analyzed by Cox regression.

RESULTS

There were 78 patients with ABMR (48 in the ST group, 30 in the BR group), 41 (53%) were men, mean age 49.5 ± 13.8 years. In ST and BR, respectively, mean serum creatinine was 267 ± 164 and 208 ± 112 µmol/L (p = 0.088), donor-specific antibodies (DSA) were positive in 75% and 97% (p = 0.022), and ABMR was acute in 50% and 33% (p = 0.149). Patient survival at 2 years was 89% in the ST and 100% in the BR group (p = 0.125). Cumulative proportion of kidney graft survival at 1 and 2 years was 67% and 53% in the ST group and 73% and 48% in the BR group, respectively, (p = 0.641). Chronic ABMR (HR 5.22, p = 0.004) was significant, while dialysis dependency at biopsy (HR 3.28, p = 0.072), serum creatinine at kidney biopsy (HR 1.003, p = 0.082), and presence of DQ-DSA (HR 3.37, p = 0.062) were borderline significant predictors of worse graft outcome. Infections were relatively common in both groups, with a trend towards more rehospitalizations due to infections in the first 6 months after treatment in the BR group (p = 0.066). In 5 patients (17%), treatment with bortezomib was discontinued prematurely due to cytopenia.

CONCLUSIONS: Bortezomib or rituximab, added to standard treatment, did not significantly improve kidney graft survival and was also not associated with significant side effects, except cytopenia in some cases. Treatment of acute ABMR resulted in better graft survival than chronic ABMR. .

摘要

背景

我们研究的目的是确定肾移植抗体介导性排斥反应（ABMR）的标准治疗与联合使用硼替佐米或利妥昔单抗的治疗结果。

方法

这项回顾性研究的队列包括2005年至2017年期间在我们国家中心接受肾移植ABMR治疗的患者，分为两组：标准（ST）组，采用血浆置换或免疫吸附、静脉注射免疫球蛋白和皮质类固醇进行标准治疗；BR组，在标准治疗基础上加用硼替佐米和/或利妥昔单抗。采用Kaplan-Meier法分析2年时的患者和移植物存活率，并通过Cox回归分析移植物存活的预测因素。

结果

有78例ABMR患者（ST组48例，BR组30例），41例（53%）为男性，平均年龄49.5±13.8岁。ST组和BR组的平均血清肌酐分别为267±164和208±112μmol/L（p = 0.088），供者特异性抗体（DSA）阳性率分别为75%和97%（p = 0.022），急性ABMR分别为50%和33%（p = 0.149）。ST组2年时的患者存活率为89%，BR组为100%（p = 0.125）。ST组1年和2年时肾移植存活的累积比例分别为67%和53%，BR组分别为73%和48%（p = 0.641）。慢性ABMR（HR 5.22，p = 0.004）具有显著意义，而活检时的透析依赖（HR 3.28，p = 0.072）、肾活检时的血清肌酐（HR 1.003，p = 0.082）和DQ-DSA的存在（HR 3.37，p = 0.062）是移植物预后较差的临界显著预测因素。两组感染都相对常见，BR组在治疗后的前6个月因感染再次住院的趋势更明显（p = 0.066）。5例患者（17%）因血细胞减少症而提前停用硼替佐米治疗。