Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Medical Center of Kidney Disease, Shanghai, China.
Department of Nephrology and Clinical Immunology, University Hospital RWTH, Aachen, Germany.
Clin Ther. 2023 Apr;45(4):364-374. doi: 10.1016/j.clinthera.2023.03.002. Epub 2023 Mar 28.
Primary membranous nephropathy (PMN) is the most frequent cause of nephrotic syndrome in adults. Rituximab monotherapy has emerged as a front-line treatment for patients with PMN, but potential markers for predicting the response to rituximab are unknown.
In this single-arm retrospective pilot study, 48 patients with PMN without previous immunosuppressive therapy were enrolled. All patients were treated with rituximab and were followed up for at least 6 months. The primary end point was the achievement of complete or partial remission at 6 months. The subsets of lymphocytes were collected at baseline, 1 month, 3 months and 6 months to identify prognostic factors for achieving remission of PMN with rituximab therapy.
A total of 58.3% of patients (28/48) achieved remission. Lower serum creatinine, greater serum albumin, and greater phospholipase A2 receptor antigen detected in kidney biopsy at baseline were found in the remission group. After multiple adjustments, a high percentage of natural killer (NK) cells at baseline, especially ≥15.7%, was strongly associated with remission (relative risk = 1.62; 95% CI, 1.00-2.62; P = 0.049), and patients with a response to rituximab had a greater mean percentage of NK cells during the follow-up period compared with nonresponders. Analysis using a receiver operating characteristic curve indicated prognostic value of the NK-cell percentage at baseline, with an area under the curve of 0.716 (95% CI, 0.556-0.876; P = 0.021).
The findings from this retrospective pilot study suggest that a high percentage, especially ≥15.7%, of NK cells at baseline might predict a response to rituximab treatment. These findings provide a basis for designing larger-scale studies to test the predictive value of NK cells in patients with PMN undergoing rituximab treatment.
原发性膜性肾病（PMN）是成人肾病综合征最常见的病因。利妥昔单抗单药治疗已成为 PMN 患者的一线治疗方法，但预测利妥昔单抗反应的潜在标志物尚不清楚。
在这项单臂回顾性试点研究中，纳入了 48 例未经先前免疫抑制治疗的 PMN 患者。所有患者均接受利妥昔单抗治疗，并至少随访 6 个月。主要终点是在 6 个月时达到完全或部分缓解。在基线、1 个月、3 个月和 6 个月时采集淋巴细胞亚群，以确定利妥昔单抗治疗 PMN 缓解的预测因素。
共有 58.3%（28/48）的患者达到缓解。缓解组的血清肌酐较低、血清白蛋白较高、肾活检中磷脂酶 A2 受体抗原较高。经多次调整后，基线时自然杀伤（NK）细胞的高百分比，尤其是≥15.7%，与缓解密切相关（相对风险 1.62；95%CI，1.00-2.62；P=0.049），且对利妥昔单抗有反应的患者在随访期间 NK 细胞的平均百分比高于无反应者。使用受试者工作特征曲线分析表明，基线时 NK 细胞百分比具有预后价值，曲线下面积为 0.716（95%CI，0.556-0.876；P=0.021）。
这项回顾性试点研究的结果表明，基线时 NK 细胞的高百分比，尤其是≥15.7%，可能预测利妥昔单抗治疗的反应。这些发现为设计更大规模的研究提供了依据，以测试 NK 细胞在接受利妥昔单抗治疗的 PMN 患者中的预测价值。
