El-Reshaid Kamel, Sallam Hossameldin Tawfik, Hakim Abbass Ali, Al-Attiyah Rajaa
Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait.
Saudi J Kidney Dis Transpl. 2012 Sep;23(5):973-8. doi: 10.4103/1319-2442.100878.
The aim of our study was to assess the role of rituximab (Mabthera) in the treatment of patients with corticosteroid-resistant and calcineurin-inhibitors ± cellcept refractory idiopathic nephrotic syndrome (INS). A total of 83 patients who had required the previous treatment for a minimum of two years were included in the study. Our protocol included the use of rituximab in four-weekly slow infusions. Five patients were excluded as they could not tolerate rituximab infusion for allergic reaction. As expected, none of the patients had a decline in the total circulating lymphocyte counts yet all had achieved decline of their initially normal CD20 to < 0.5% one month after infusion. The decline persisted for eight to ten months later. In the minimal change disease (MCD) group, 31 of the 32 patients had complete remission (CR) and were off any immunosuppressive therapy and one of the previous non-responders (NR) did not respond. Excluding two patients who had required retreatment, the others remained in CR (17 up to 28 months and six up to 36 months). Treatment with rituximab resulted in amelioration of NS in 17 of the 18 patients with focal segmental glomerulosclerosis (FSGS), while only one patient remained NR. Although renal function remained stable, proteinuria reappeared by eight to 12 months. Retreatment with rituximab resulted in a similar response with stable kidney function. In the 28 patients with membranous glomerulopathy (MG), 24 had achieved CR. Two patients failed to respond and two had partial remission. By 12 months, all patients relapsed. The response was within one month following treatment in patient with MCD, but was gradual within three months in FSGS and MG. Relapsers in all groups responded in a similar pattern to repeat dosing with the drug subsequently. Our prospective study represents an adequate number of patients with biopsy-proven subgroups of INS in both children and adults with long-term follow-up of treatment with rituximab. The drug is effective and safe for treatment of patients refractory to the conventional agents.
我们研究的目的是评估利妥昔单抗（美罗华）在治疗对皮质类固醇耐药且对钙调神经磷酸酶抑制剂±骁悉难治的特发性肾病综合征（INS）患者中的作用。共有83名此前至少接受过两年治疗的患者纳入本研究。我们的方案包括每四周缓慢输注利妥昔单抗。5名患者因对利妥昔单抗输注产生过敏反应而无法耐受，被排除在外。正如预期的那样，所有患者循环淋巴细胞总数均未下降，但在输注后1个月，所有患者最初正常的CD20均降至<0.5%。这种下降持续了8至10个月。在微小病变病（MCD）组中，32名患者中有31名完全缓解（CR），停用了任何免疫抑制治疗，1名先前无反应者（NR）仍无反应。排除2名需要再次治疗的患者后，其他患者仍处于CR状态（17名长达28个月，6名长达36个月）。利妥昔单抗治疗使18名局灶节段性肾小球硬化（FSGS）患者中的17名肾病得到改善，而只有1名患者仍为NR。尽管肾功能保持稳定，但蛋白尿在8至12个月时再次出现。再次使用利妥昔单抗治疗产生了类似的反应，肾功能稳定。在28名膜性肾小球病（MG）患者中，24名实现了CR。2名患者无反应，2名部分缓解。到12个月时，所有患者均复发。MCD患者在治疗后1个月内出现反应，但FSGS和MG患者在3个月内反应逐渐出现。所有组中的复发者对随后重复给药的反应模式相似。我们的前瞻性研究纳入了足够数量经活检证实为INS亚组的儿童和成人患者，并对利妥昔单抗治疗进行了长期随访。该药物对传统药物难治的患者治疗有效且安全。
