Kidney Health Service, Royal Brisbane and Women's Hospital, Level 9 Ned Hanlon Building, Butterfield Street, Herston, Queensland, 4029, Australia.
Department of Renal Medicine, Townsville University Hospital, Douglas, QLD, Australia.
BMC Nephrol. 2022 Apr 7;23(1):134. doi: 10.1186/s12882-022-02761-3.
Membranous Nephropathy (MN) is a common cause of nephrotic syndrome (NS) in adults. Recognition of MN as an antibody mediated autoimmune disease has enabled the introduction of anti-B-cell therapy. Rituximab, a type I anti-CD20 antibody has been used in the management of MN, but has a 35-45% failure rate. Obinutuzumab, a fully humanised type II anti-CD20 monoclonal antibody produces greater CD20 depletion and is superior to rituximab in the treatment of certain B-cell malignancies. In the two reports published to date involving nine patients with M-type phospholipase A2 receptor (PLA2R) associated MN (six of whom were rituximab resistant), treatment with obinutuzumab lead to immunological remission (IR) in 75% of patients, with improvement of proteinuria, normalisation of serum albumin and stable renal function in all patients.
We report on two cases of PLA2R-associated MN, two males aged 33 and 36-years, who presented with NS and bilateral sub massive pulmonary emboli requiring anticoagulation. Both were diagnosed serologically as PLA2R-associated MN where a renal biopsy was initially deferred due to bleeding risk on anticoagulation, but later confirmed. Both patients were refractory to multiple lines of therapy including rituximab, but achieved IR, normalistation of serum albumin, improved proteinuria and stable renal function with obinutuzumab.
Our cases add to the current limited literature on the successful use of obinutuzumab in PLA2R associated MN refractory to standard therapy including rituximab.
膜性肾病（MN）是成人肾病综合征（NS）的常见病因。将 MN 识别为抗体介导的自身免疫性疾病，使抗 B 细胞治疗得以引入。利妥昔单抗是一种 I 型抗 CD20 抗体，已用于 MN 的治疗，但失败率为 35-45%。奥滨尤妥珠单抗，一种完全人源化的 II 型抗 CD20 单克隆抗体，可产生更大的 CD20 耗竭，在治疗某些 B 细胞恶性肿瘤方面优于利妥昔单抗。迄今为止，在涉及九名 M 型磷脂酶 A2 受体（PLA2R）相关 MN 患者的两份报告中（其中六名对利妥昔单抗耐药），奥滨尤妥珠单抗治疗导致 75%的患者出现免疫缓解（IR），所有患者的蛋白尿改善、血清白蛋白正常化和肾功能稳定。
我们报告两例 PLA2R 相关 MN 患者，两名男性，年龄分别为 33 岁和 36 岁，表现为 NS 和双侧亚大面积肺栓塞，需要抗凝治疗。两者均通过血清学诊断为 PLA2R 相关 MN，由于抗凝出血风险，最初推迟了肾活检，但后来得到了证实。两名患者均对包括利妥昔单抗在内的多种治疗方案耐药，但奥滨尤妥珠单抗治疗后均实现了 IR、血清白蛋白正常化、蛋白尿改善和肾功能稳定。
我们的病例增加了目前关于奥滨尤妥珠单抗在 PLA2R 相关 MN 中的成功应用的有限文献，这些患者对包括利妥昔单抗在内的标准治疗耐药。
