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复杂型肾病综合征患者中利妥昔单抗相关低丙种球蛋白血症的发病率及危险因素

Incidence and risk factors of rituximab-associated hypogammaglobulinemia in patients with complicated nephrotic syndrome.

作者信息

Inoki Yuta, Kamei Koichi, Nishi Kentaro, Sato Mai, Ogura Masao, Ishiguro Akira

机构信息

Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan.

Center for Postgraduate Education and Training, National Center for Child Health and Development, Tokyo, Japan.

出版信息

Pediatr Nephrol. 2022 May;37(5):1057-1066. doi: 10.1007/s00467-021-05304-4. Epub 2021 Oct 4.

Abstract

BACKGROUND

Hypogammaglobulinemia is a major adverse event after rituximab treatment; however, the precise incidence and risk factors are unclear in complicated steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS) patients.

METHODS

This was a single-center, retrospective, observational study. Patients who received a single dose of rituximab for complicated SDNS or FRNS between February 2007 and May 2019 were enrolled. Serum IgG levels were plotted, and their trends were evaluated after rituximab treatment. The incidence of transient and persistent hypogammaglobulinemia was examined, and risk factors were calculated by multivariate analysis using logistic regression.

RESULTS

We enrolled 103 patients who received 238 single doses of rituximab. Hypogammaglobulinemia was observed in 58.4% of the patients at least once after a single dose of rituximab treatment and 22.3% developed persistent hypogammaglobulinemia. Serum IgG levels gradually increased during B-cell depletion, and patients with low serum IgG levels at rituximab treatment had persistent hypogammaglobulinemia. Repeated courses of rituximab treatment increased the incidence of hypogammaglobulinemia. A past history of steroid-resistant nephrotic syndrome (SRNS) (odds ratio [OR] = 10.02; 95% confidence interval [CI] = 2.65-37.81; P < 0.001) and low serum IgG levels at rituximab treatment (OR = 7.63; 95% CI = 2.10-27.71; P = 0.002) was significantly associated with hypogammaglobulinemia in multivariate analysis.

CONCLUSIONS

Hypogammaglobulinemia is a frequent adverse event after rituximab treatment, although IgG levels slightly increase during B-cell depletion. Low serum IgG levels at rituximab treatment and a past history of SRNS are significant risk factors for the development of hypogammaglobulinemia after rituximab treatment.

摘要

背景

低丙种球蛋白血症是利妥昔单抗治疗后的主要不良事件;然而,在复杂的激素依赖型或频繁复发的肾病综合征(SDNS/FRNS)患者中,其确切发病率和危险因素尚不清楚。

方法

这是一项单中心、回顾性观察研究。纳入2007年2月至2019年5月期间因复杂SDNS或FRNS接受单剂量利妥昔单抗治疗的患者。绘制血清IgG水平图,并评估利妥昔单抗治疗后的变化趋势。检查短暂性和持续性低丙种球蛋白血症的发生率,并使用逻辑回归通过多变量分析计算危险因素。

结果

我们纳入了103例接受238单剂量利妥昔单抗治疗的患者。58.4%的患者在单剂量利妥昔单抗治疗后至少出现一次低丙种球蛋白血症,22.3%发生持续性低丙种球蛋白血症。在B细胞耗竭期间血清IgG水平逐渐升高,利妥昔单抗治疗时血清IgG水平低的患者出现持续性低丙种球蛋白血症。重复使用利妥昔单抗治疗会增加低丙种球蛋白血症的发生率。多变量分析显示,既往有激素抵抗型肾病综合征(SRNS)病史(比值比[OR]=10.02;95%置信区间[CI]=2.65-37.81;P<0.001)和利妥昔单抗治疗时血清IgG水平低(OR=7.63;95%CI=2.10-27.71;P=0.002)与低丙种球蛋白血症显著相关。

结论

尽管在B细胞耗竭期间IgG水平略有升高,但低丙种球蛋白血症是利妥昔单抗治疗后常见的不良事件。利妥昔单抗治疗时血清IgG水平低和既往有SRNS病史是利妥昔单抗治疗后发生低丙种球蛋白血症的重要危险因素。

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