Supplementary Material for: Immunosuppressive Therapy in Primary Membranous Nephropathy with Compromised Renal Function

<b><i>Introduction:</i></b> Renal dysfunction at presentation is uncommon in primary membranous nephropathy (PMN). The data on the outcome of PMN patients with renal dysfunction at outset are scarce. The objective of the current study was to report the clinical outcomes of PMN patients with renal dysfunction. <b><i>Material and Methods:</i></b> This prospective longitudinal observational study included PMN patients (both incident and treatment resistant) with an estimated glomerular filtration rate of &lt;60 mL/min/1.73 m². Immunosuppressive treatment was as per the unit’s protocol. Patients were evaluated for proteinuria, creatinine, and serum albumin at monthly intervals for 6 months, then quarterly for a year, and then biannually. Both serum and tissue anti-PLA2R were performed at baseline. Outcome: Percentage of patients achieving clinical remission. <b><i>Results:</i></b> Sixty-four adults met study criteria and were analysed. The median (IQR) age of the patients was 48 (40, 56) years. PMN was PLA2R related in 52 (81.3%) patients. Twenty-eight (43.8%) and 30 (46.9%) patients were in remission at 12 months and at the end of the study [median (IQR) follow up: 24 months (12, 35)], respectively. Eight (12.5%) had progressed to end-stage renal disease at the last follow-up. Median (IQR) baseline anti-PLA2R titre was 150.1 RU/mL (38.5, 308). Nineteen (61.3%) and 18 (58.1%) patients with &gt;90% reduction in anti-PLA2R titres at 12 months were in clinical remission at 12 months and at the end of the follow-up, respectively. Both cyclical cyclophosphamide/steroids (cCYC/GC) and rituximab were equally effective in inducing remission, but rituximab had a favourable adverse event profile compared to cCYC/GC. <b><i>Conclusion:</i></b> To conclude, both cCYC/GC and rituximab are equally effective in inducing remission of nephrotic state with compromised renal function due to PMN. Immunosuppression induces remission in up to 50% PMN patients with CKD-stage 3–4.

<b><i>引言：</i></b> 原发性膜性肾病（primary membranous nephropathy, PMN）患者初诊时伴肾功能不全的情况并不多见，目前针对初诊即伴肾功能不全的PMN患者的预后相关研究数据仍较为匮乏。本研究旨在报告此类伴肾功能不全的PMN患者的临床转归。
<b><i>材料与方法：</i></b> 本项前瞻性纵向观察研究纳入了估算肾小球滤过率（estimated glomerular filtration rate）＜60 mL/min/1.73 m²的PMN患者，包括初发患者与治疗抵抗患者。免疫抑制治疗方案遵循本中心的诊疗规范。研究人员分别于治疗前6个月内每月、后续1年内每3个月、之后每半年对患者的蛋白尿、肌酐及血清白蛋白水平进行评估。所有受试者均于基线时检测血清及组织抗PLA2R抗体（anti-PLA2R）。本研究的主要结局指标为达到临床缓解的患者占比。
<b><i>结果：</i></b> 最终共有64名成年患者符合研究纳入标准并被纳入分析。患者年龄的中位数（四分位距）为48（40，56）岁，其中52例（81.3%）为PLA2R相关性PMN。分别有28例（43.8%）患者在随访12个月时、30例（46.9%）患者在研究结束时达到临床缓解；本研究的中位（四分位距）随访时长为24个月（12，35）。8例（12.5%）患者在末次随访时进展为终末期肾病。基线时抗PLA2R抗体滴度的中位数（四分位距）为150.1 RU/mL（38.5，308）。在随访12个月时抗PLA2R抗体滴度下降超过90%的患者中，分别有19例（61.3%）在12个月时达到临床缓解、18例（58.1%）在随访结束时达到临床缓解。间断环磷酰胺联合糖皮质激素（cyclical cyclophosphamide/steroids, cCYC/GC）与利妥昔单抗在诱导缓解方面疗效相当，但利妥昔单抗的不良事件谱更具优势。
<b><i>结论：</i></b> 综上，对于因PMN导致肾功能受损的肾病综合征患者，cCYC/GC与利妥昔单抗在诱导缓解方面疗效相当。免疫抑制治疗可使多达50%的慢性肾脏病（chronic kidney disease, CKD）3~4期PMN患者达到临床缓解。