Supplementary Material for: Efficacy of Rituximab for Minimal Change Disease and Focal Segmental Glomerulosclerosis with Frequently Relapsing or Steroid-Dependent Nephrotic Syndrome in Adults: A Chinese Multicenter Retrospective Study

Introduction Rituximab has been proven effective and safe in pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). We aimed to analyze the efficacy and safety of rituximab in adult FR/SDNS patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Methods A retrospective cohort study at three nephrology centers in China included adult FR/SDNS patients with biopsy-proven MCD or FSGS. Primary outcomes were relapse frequency and first relapse-free survival time. Adverse events were well recorded and logistic regression analyses were used to investigate risk factors of relapse. Results Eighty-one patients (age 25.0 years, interquartile range, 20.0-40.5; 67% males; 82.7% MCD) received an average rituximab dose of 1393.8 ± 618.7 mg/2y during the two-year follow-up period. The relapse frequency, calculated as the ratio of relapse times to follow-up years, significantly decreased after rituximab treatment [0.04 (0.00, 0.08) vs. 1.71 (1.00, 2.45), P < 0.001]. The first relapse-free survival time was 16.7 ± 8.0 months. Fifty-seven patients (70.4%) achieved cessation of corticosteroids and immunosuppressants within three months after the first rituximab infusion. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. Low serum albumin level before rituximab and high CD56+CD16+ natural killer cell count after rituximab were independent risk factors of relapse within two years after rituximab treatment. Conclusion Rituximab was proven an effective and safe treatment option for adult FR/SDNS patients with MCD or FSGS in maintaining disease remission and minimizing corticosteroid exposure.

引言 利妥昔单抗（Rituximab）已被证实对频繁复发型或激素依赖型肾病综合征（frequently relapsing or steroid-dependent nephrotic syndrome, FR/SDNS）儿童患者安全有效。本研究旨在分析利妥昔单抗在合并最小病变型肾病（minimal change disease, MCD）及局灶节段性肾小球硬化（focal segmental glomerulosclerosis, FSGS）的成年FR/SDNS患者中的有效性与安全性。
方法 本研究为一项在中国三家肾脏病中心开展的回顾性队列研究，纳入经肾活检证实为MCD或FSGS的成年FR/SDNS患者。主要结局指标为复发频率与首次无复发生存时间。研究对所有不良事件进行了详细记录，并采用logistic回归分析探讨复发的危险因素。
结果 共81例患者纳入分析，年龄中位数为25.0岁（四分位数间距：20.0~40.5岁），男性占比67%，82.7%的患者病理类型为MCD。在为期2年的随访周期内，患者平均接受利妥昔单抗剂量为1393.8±618.7 mg/2年。以复发次数与随访年数比值计算的复发频率，在利妥昔单抗治疗后显著降低[0.04（0.00，0.08）vs. 1.71（1.00，2.45），P<0.001]。患者的首次无复发生存时间为16.7±8.0个月。57例患者（70.4%）在首次利妥昔单抗输注后的3个月内实现了糖皮质激素与免疫抑制剂的停用。不良事件多为轻度，未观察到严重的治疗相关不良事件。利妥昔单抗治疗前的低血清白蛋白水平，以及治疗后的高CD56+CD16+自然杀伤细胞计数，均为治疗后2年内复发的独立危险因素。
结论 本研究证实，利妥昔单抗是治疗合并MCD或FSGS的成年FR/SDNS患者的安全有效方案，可有效维持疾病缓解并减少糖皮质激素暴露。