Aleš Rigler Andreja, Jerman Alexander, Orsag Aleša, Kojc Nika, Kovač Damjan, Škoberne Andrej, Borštnar Špela, Večerić Haler Željka, Avguštin Nuša, Kveder Radoslav, Ferluga Dušan, Vizjak Alenka, Lindič Jelka
Clin Nephrol. 2017;88(13):27-31. doi: 10.5414/CNP88FX07.
Treatment of idiopathic membranous nephropathy with rituximab was introduced more than a decade ago following experimental data that suggested involvement of B-cell-mediated reactions in its pathogenesis. It was a logical step towards a more selective therapy with less severe side effects as compared to the recommended first-line immunosuppressive therapy with corticosteroids and different immunosuppressant drugs.
We retrospectively analyzed the anonymous data of patients who were treated with rituximab for idiopathic membranous nephropathy at our institution from January 2006 to July 2016. Daily proteinuria and serum creatinine were analyzed 3, 6, 9, and 12 months after rituximab application. The patients were divided into 4 groups according to proteinuria. We separately analyzed remission rates in the whole group and in groups with different quantity of daily proteinuria. Other history data and laboratory parameters were also compared within different groups of patients.
The study involved 29 rituximab treatments in 26 patients: 7 (26.9%) female and 19 (73.1%) male patients. In 16 out of 29 treatment cases (55.1%), patients had been previously treated with cyclophosphamide and steroids, or cyclosporine with low dose of steroids, or both. In 72.4% of patients, antiphospholipase A receptor antibodies were present. In 2 cases of treatment (6.9%), patients received rituximab 375 mg/m of body surface area in 3 and 4 weekly doses, respectively. In all other cases, repeated rituximab applications were given as needed according to the levels of circulating CD-20 B-cells. The total remission rate in our cohort of patients was 37.9% (11 out of 29 cases). The average serum creatinine in the group of patients who achieved remission was significantly lower than in the group without remission (86.5 vs. 155.5 µmol/L, p = 0.003). There was no difference in the duration of the disease prior to treatment with rituximab between the groups (53.6 and 56.4 months, respectively). The remission rate was highest in the group with daily proteinuria less than 4 g per day (83.3%). There were no remissions in the group of patients with daily proteinuria more than 12 g per day.
CONCLUSION: The remission rate after rituximab treatment in our cohort of patients with idiopathic membranous nephropathy was lower than in other studies. The reason for this is possibly the application of a single dose of rituximab in the majority of patients, which might have been insufficient in patients with higher proteinuria. .
十多年前,基于实验数据表明B细胞介导的反应参与特发性膜性肾病的发病机制,利妥昔单抗开始用于治疗特发性膜性肾病。与推荐的一线使用皮质类固醇和不同免疫抑制药物的免疫抑制疗法相比,这是迈向更具选择性、副作用更小的治疗的合理一步。
我们回顾性分析了2006年1月至2016年7月在我院接受利妥昔单抗治疗特发性膜性肾病患者的匿名数据。在应用利妥昔单抗后3、6、9和12个月分析每日蛋白尿和血清肌酐。根据蛋白尿情况将患者分为4组。我们分别分析了整个组以及每日蛋白尿不同量分组的缓解率。还比较了不同患者组的其他病史数据和实验室参数。
该研究涉及26例患者接受29次利妥昔单抗治疗:女性7例(26.9%),男性19例(73.1%)。在29例治疗病例中的16例(55.1%)中,患者此前曾接受环磷酰胺和类固醇治疗,或低剂量类固醇联合环孢素治疗,或两者皆用。72.4%的患者存在抗磷脂酶A受体抗体。在2例治疗(6.9%)中,患者分别以375mg/m²体表面积、每3周和4周一次的剂量接受利妥昔单抗治疗。在所有其他病例中,根据循环CD-20 B细胞水平按需重复应用利妥昔单抗。我们的患者队列总缓解率为37.9%(29例中的11例)。缓解组患者的平均血清肌酐显著低于未缓解组(86.5对155.5µmol/L,p = 0.003)。两组在接受利妥昔单抗治疗前的病程无差异(分别为53.6个月和56.4个月)。每日蛋白尿少于4g/天的组缓解率最高(83.3%)。每日蛋白尿超过12g/天的患者组无缓解病例。
我们的特发性膜性肾病患者队列中利妥昔单抗治疗后的缓解率低于其他研究。原因可能是大多数患者使用了单剂量利妥昔单抗,这对于蛋白尿较高的患者可能不足。