Kojima Daiki, Yamaguchi Shintaro, Hashiguchi Akinori, Hayashi Kaori, Uchiyama Kiyotaka, Yoshimoto Norifumi, Adachi Keika, Nakayama Takashin, Nishioka Ken, Tajima Takaya, Morimoto Kohkichi, Yoshino Jun, Yoshida Tadashi, Monkawa Toshiaki, Kanda Takeshi, Itoh Hiroshi
Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Front Med (Lausanne). 2023 Jan 9;9:1037032. doi: 10.3389/fmed.2022.1037032. eCollection 2022.
Idiopathic multicentric Castleman disease (iMCD) is a systemic and polyclonal lymphoproliferative disease involving multiple organs, including the kidneys, due to the overproduction of interleukin-6 (IL-6). Recently, several reports have suggested that excessive IL-6 actions in iMCD could have a causal relationship with the development of diverse histopathological renal manifestations that cause nephrotic syndrome. However, the treatment for such cases remains unclear. We report a series of three cases of nephrotic syndrome due to iMCD that helps to delineate the importance of early and continuous therapy with the anti-interleukin-6 receptor antibody tocilizumab. First, treatment was suspended for infectious control, and the patient presented with nephrotic syndrome due to diffuse mesangial and endocapillary hypercellularity without immune deposits complicating acute kidney injury. Second, iMCD was treated with prednisolone alone. The patient suddenly developed nephrotic syndrome due to immune-complex glomerulonephritis, not otherwise specified, complicated with acute kidney injury. In the third case, nephrotic syndrome secondary to membranous glomerulonephritis was diagnosed, with a skin rash and IgE antibodies to tocilizumab, and was therefore treated with prednisolone alone. In contrast to the first two cases, the third progressed to end-stage renal disease on hemodialysis. Taken together, this series suggests that clinicians should maintain clinical vigilance for iMCD as a possible underlying component of nephrotic syndrome, since iMCD presents with a variety of renal pathologies. Prompt initiation and continuous administration of tocilizumab are likely key determinants of renal outcomes in such cases. In particular, when tocilizumab is suspended due to infection or in the perioperative period, consideration of its expeditious resumption should be made, taking into account both the withdrawal period and systemic conditions.
特发性多中心Castleman病（iMCD）是一种系统性多克隆淋巴细胞增生性疾病，由于白细胞介素-6（IL-6）过度产生，可累及包括肾脏在内的多个器官。最近，有几份报告表明，iMCD中IL-6的过度作用可能与导致肾病综合征的多种组织病理学肾脏表现的发展存在因果关系。然而，此类病例的治疗方法仍不明确。我们报告了3例因iMCD导致肾病综合征的病例系列，这有助于阐明早期和持续使用抗白细胞介素-6受体抗体托珠单抗治疗的重要性。第一例，为控制感染暂停治疗，患者出现肾病综合征，原因是弥漫性系膜和毛细血管内细胞增多，无免疫沉积物，并发急性肾损伤。第二例，仅用泼尼松龙治疗iMCD。患者突然因未另行特指的免疫复合物性肾小球肾炎并发急性肾损伤而出现肾病综合征。第三例，诊断为膜性肾小球肾炎继发的肾病综合征，伴有皮疹和抗托珠单抗IgE抗体，因此仅用泼尼松龙治疗。与前两例不同，第三例进展为需血液透析的终末期肾病。综上所述，该病例系列表明，临床医生应保持警惕，将iMCD视为肾病综合征可能的潜在病因，因为iMCD可表现为多种肾脏病理类型。在此类病例中，及时启动并持续使用托珠单抗可能是肾脏预后的关键决定因素。特别是，当因感染或围手术期停用托珠单抗时，应考虑在考虑停药期和全身状况的情况下尽快恢复用药。
