Zhou Zijian, Zou Yijing, Ke Ben, Shen Wen
The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People's Republic of China.
Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.
Immunotargets Ther. 2025 May 6;14:515-522. doi: 10.2147/ITT.S512451. eCollection 2025.
Cyclophosphamide, tacrolimus, and rituximab (RTX) are first-line treatments for idiopathic membranous nephropathy (IMN), regardless of PLA2R status. While the efficacy of RTX in IMN patients with PLA2R-positive has been well-documented, its effectiveness in IMN patients with PLA2R-negative remains understudied. This study aimed to evaluate the efficacy and adverse events of these three treatment regimens in IMN patients with PLA2R-negative.
This study included 46 PLA2R-negative IMN patients confirmed by renal biopsy and immunofluorescence from the Department of Nephrology, the Second Affiliated Hospital of Nanchang University between September 2021 and October 2023. We compared clinical remission rates, and side effects at 3, 6, and 12 months follow-up in 14 patients who received prednisolone combined with cyclophosphamide (cyclophosphamide group), in 11 patients who treated with prednisolone combined with tacrolimus (tacrolimus group), and 21 patients who treated with rituximab (RTX group).
Baseline characteristics were similar among the three groups. At the 12-month follow-up, the complete response rate was significantly higher in the cyclophosphamide and tacrolimus groups compared to the RTX group ( = 0.029). However, there were no significant differences in cumulative complete remission rates or cumulative composite remission rates among the three groups during the follow-up period ( = 0.192, = 0.212). Severe adverse events occurred in all groups, but the differences were not statistically significant ( > 0.05).
Cyclophosphamide and tacrolimus appear to offer long-term benefits for PLA2R-negative IMN patients, with tacrolimus demonstrating superior efficacy among the treatment options evaluated. These insights offer important guidance for clinical decision-making in the management of PLA2R-negative IMN. However, further large-scale, multicenter studies with long-term follow-up are necessary to confirm these findings.
环磷酰胺、他克莫司和利妥昔单抗（RTX）是特发性膜性肾病（IMN）的一线治疗药物，无论患者是否存在磷脂酶A2受体（PLA2R）。虽然RTX在PLA2R阳性的IMN患者中的疗效已有充分记录，但其在PLA2R阴性的IMN患者中的有效性仍研究不足。本研究旨在评估这三种治疗方案在PLA2R阴性的IMN患者中的疗效和不良事件。
本研究纳入了2021年9月至2023年10月期间南昌大学第二附属医院肾内科经肾活检和免疫荧光确诊的46例PLA2R阴性的IMN患者。我们比较了14例接受泼尼松联合环磷酰胺治疗的患者（环磷酰胺组）、11例接受泼尼松联合他克莫司治疗的患者（他克莫司组）和21例接受利妥昔单抗治疗的患者（RTX组）在3个月、6个月和12个月随访时的临床缓解率及副作用。
三组患者的基线特征相似。在12个月的随访中，环磷酰胺组和他克莫司组的完全缓解率显著高于RTX组（P = 0.029）。然而，在随访期间，三组的累积完全缓解率或累积综合缓解率无显著差异（P = 0.192，P = 0.212）。所有组均发生了严重不良事件，但差异无统计学意义（P > 0.05）。
环磷酰胺和他克莫司似乎为PLA2R阴性的IMN患者带来长期益处，在评估的治疗方案中，他克莫司显示出更好的疗效。这些见解为PLA2R阴性的IMN管理中的临床决策提供了重要指导。然而，需要进一步进行大规模、多中心的长期随访研究来证实这些发现。
