Vink Coralien H, Wetzels Jack F M, Logt Anne-Els van de
Department of Nephrology, Radboud institute of Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
Kidney Int Rep. 2024 Sep 12;9(12):3439-3445. doi: 10.1016/j.ekir.2024.08.033. eCollection 2024 Dec.
Standard treatment with cyclophosphamide (CP) or rituximab (RTX) is suboptimal. We adapted and used the low-dose regimen used in vasculitis (RTX 2 × 1000 mg, CP 1.5 mg/kg/d × 8 weeks, and prednisone [i.v. 2 × 1 g + 3 weeks oral starting at 1 mg/kg]).
High-risk, anti-PLA2R antibodies (PLA2Rab)-positive patients with membranous nephropathy (MN) were included in this single-arm prospective cohort study. PLA2Rab levels were regularly measured. We report the PLA2Rab kinetics and overall immunological and clinical remission (CR) rate.
We analyzed 26 patients (15 males, aged 57 ± 14 years, PLA2Rab titer 176 [115-460] RU/ml, serum creatinine 128 [102-136] μmol/l, serum albumin 18 [14-21] g/l, and urinary protein-to-creatinine ratio [uPCR] 7.1 [5.7-10] g/10 mmol). Within 8 weeks immunological remission (IR) (enzyme-linked immunosorbent assay < 14 RU/ml) was 88 %. Proteinuria remission after initial therapy developed in 21 patients. Seven patients received renewed therapy, which resulted in proteinuria remission in all. IR and CR were associated with baseline PLA2Rab tertile. Five of 7 patients in need of additional therapy were identified at 4 weeks after start of therapy by PLA2Rab half-life (T) > 7 days. Serious adverse events occurred in 4 patients. Adverse events were mild; leukopenia was most frequent.
Low-dose triple therapy induced a rapid IR and CR in most patients. Patients with insufficient clinical response were characterized by high baseline PLA2Rab levels and longer PLA2Rab T. Assessment of PLA2Rab levels within 2 to 4 weeks after start of therapy may enable to identify patients who need more intensive therapy.
环磷酰胺（CP）或利妥昔单抗（RTX）的标准治疗效果欠佳。我们调整并采用了用于血管炎的低剂量方案（RTX 2×1000mg，CP 1.5mg/kg/d×8周，以及泼尼松[静脉注射2×1g + 从1mg/kg开始口服3周]）。
本单臂前瞻性队列研究纳入了高危、抗磷脂酶A2受体抗体（PLA2Rab）阳性的膜性肾病（MN）患者。定期检测PLA2Rab水平。我们报告了PLA2Rab动力学以及总体免疫和临床缓解（CR）率。
我们分析了26例患者（15例男性，年龄57±14岁，PLA2Rab滴度176[115 - 460]RU/ml，血清肌酐128[102 - 136]μmol/l，血清白蛋白18[14 - 21]g/l，尿蛋白肌酐比值[uPCR]7.1[5.7 - 10]g/10mmol）。8周内免疫缓解（IR）（酶联免疫吸附测定<14RU/ml）率为88%。初始治疗后21例患者蛋白尿缓解。7例患者接受了再次治疗，所有患者蛋白尿均缓解。IR和CR与基线PLA2Rab三分位数相关。7例需要额外治疗的患者中有5例在治疗开始后4周通过PLA2Rab半衰期（T）>7天被识别。4例患者发生严重不良事件。不良事件为轻度；白细胞减少最为常见。
低剂量三联疗法在大多数患者中诱导了快速的IR和CR。临床反应不足的患者特征为基线PLA2Rab水平高且PLA2Rab T较长。在治疗开始后2至4周评估PLA2Rab水平可能有助于识别需要更强化治疗的患者。
