A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction
A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction
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DOI：
10.1681/asn.2016060640
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发表时间：
2017-04-01
影响因子：
13.6
通讯作者：
Fervenza, Fernando C.
中科院分区：
文献类型：
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作者：
Lafayette, Richard A.;Canetta, Pietro A.;Fervenza, Fernando C.
IGA肾病常导致进展性CKD。尽管人们对在标准治疗中添加免疫抑制剂感兴趣，但最近的几项研究对这些药物的有效性提出了质疑。消耗产生抗体的B细胞可能提供一种新的治疗方法。在这项为期一年多的开放式多中心研究中，我们随机选择了34名经活检证实的IgA肾病和蛋白尿的成人患者，每天服用血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂，血压控制良好，EGFR=50%的蛋白尿水平降低。血清半乳糖缺乏性IgA1水平(范围)为1.4(0.8-2.4)mg/dl，蛋白尿为2.1(0.6-5.3)g/d。利妥昔单抗治疗耗尽B细胞，耐受性良好。EGFR在两组中均无变化。与基线或对照组相比，利妥昔单抗没有改变蛋白尿水平；3名EAC患者的半乳糖缺乏IgA1抗体没有改变。在这项试验中，利妥昔单抗治疗没有显著改善肾功能或一年以上评估的蛋白尿。尽管利妥昔单抗有效地耗尽了B细胞，但它未能降低血清中缺乏半乳糖的IgA1和抗缺乏半乳糖的IgA1抗体的水平。利妥昔单抗缺乏疗效，至少在这个阶段和IgA肾病的严重性，可能反映了利妥昔单抗未能降低在IgA肾病中具有显著致病作用的特定抗体的水平。
IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR= 50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 ortinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in eac antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy.