Nada Taishi, Kamei Koichi, Nishi Kentaro, Uchimura Toru, Inaba Aya, Ogura Masao, Hamada Riku, Hataya Hiroshi, Ito Shuichi
Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
Department of Pediatrics, Yokohama City University Medical Center, 4-57 Urafune-Cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan.
Clin Exp Nephrol. 2025 Sep 3. doi: 10.1007/s10157-025-02744-2.
Maintenance therapy using immunosuppressive agents after rituximab can be effective for sustaining remission in childhood-onset refractory frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS). We evaluated the long-term outcome of mycophenolate mofetil (MMF) after rituximab.
We conducted a multicenter, retrospective cohort study of patients with childhood-onset refractory FRNS/SDNS who received MMF as maintenance therapy after a single dose of rituximab and were followed up ≥ 2 years at three pediatric renal centers. Relapses, additional treatment, risk factors for relapse, and adverse events were analyzed.
We enrolled 106 patients, and the median follow-up was 7.2 years. Forty-seven (44%) patients had no relapse under MMF, and the 50% relapse-free survival was 3.2 years during MMF administration. Sixty-one (58%) patients required additional rituximab during the observation period. The mean annual number of relapses before the first rituximab treatment versus 1 year after rituximab initiation was 3.7 (standard deviation: 1.3) versus 0.4 (standard deviation: 0.8) times (p < 0.0001). Sixty-six of 74 (89%) patients could discontinue calcineurin inhibitors within 1 year after rituximab. MMF < 1000 mg/m was an independent significant risk factor for the first relapse (p = 0.03). No fatal adverse events and 23 episodes of infection requiring hospitalization were observed during the study period.
MMF after a single dose of rituximab is safe and effective in achieving a long relapse-free period and discontinuing a calcineurin inhibitor in patients with refractory FRNS/SDNS.
利妥昔单抗后使用免疫抑制剂进行维持治疗对于维持儿童期起病的难治性频繁复发肾病综合征/激素依赖型肾病综合征（FRNS/SDNS）的缓解可能有效。我们评估了利妥昔单抗后霉酚酸酯（MMF）的长期疗效。
我们对儿童期起病的难治性FRNS/SDNS患者进行了一项多中心回顾性队列研究，这些患者在单剂量利妥昔单抗后接受MMF作为维持治疗，并在三个儿科肾脏中心进行了≥2年的随访。分析了复发情况、额外治疗、复发危险因素和不良事件。
我们纳入了106例患者，中位随访时间为7.2年。47例（44%）患者在MMF治疗下未复发，MMF治疗期间的50%无复发生存期为3.2年。61例（58%）患者在观察期内需要额外使用利妥昔单抗。首次利妥昔单抗治疗前每年的平均复发次数与利妥昔单抗开始后一年相比为3.7次（标准差：1.3）与0.4次（标准差：0.8）（p<0.0001）。74例患者中有66例（89%）在利妥昔单抗后1年内可停用钙调神经磷酸酶抑制剂。MMF<1000mg/m是首次复发独立的显著危险因素（p=0.03）。研究期间未观察到致命不良事件，有23例感染需要住院治疗。
单剂量利妥昔单抗后使用MMF对于难治性FRNS/SDNS患者实现长期无复发期和停用钙调神经磷酸酶抑制剂是安全有效的。
