Dillon John J, Hladunewich Michelle, Haley William E, Reich Heather N, Cattran Daniel C, Fervenza Fernando C
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Clin Nephrol. 2012 Apr;77(4):290-5. doi: 10.5414/cn107299.
Type I membranoproliferative glomerulonephritis (MPGN) is an immune-complex disease with a relatively poor prognosis. It has no established treatment in adults. Our hypothesis was that this disease would respond to B cell depletion with rituximab, an anti-CD20 monoclonal antibody.
We conducted an openlabel trial, in Canada and the United States, of rituximab in 6 adult patients with Type I MPGN (4 idiopathic, 2 with cryoglobulinemia). The rituximab dose was 1,000 mg intravenously on Day 1 and on Day 15. The patients were followed for 1 year. The primary outcome was the change in proteinuria.
Peripheral blood B cells were suppressed, after rituximab, in all patients. The mean urinary protein excretion was 3.9 ± 2.0 g/d before treatment. Proteinuria fell in all patients, at all-time points, after rituximab administration. The difference was statistically significant (p < 0.05) at 6, 9 and 12 months, but not at 3 months. The minimum mean urinary protein excretion was 1.4 ± 1.4 g/d at 9 months. There were 2 complete and 3 partial remissions among the 6 patients. The creatinine clearance did not change significantly over the course of the study. There were no adverse effects.
Rituximab reduced proteinuria among patients with Type I MPGN. This trial suggests that B cells may play a role in this disease and that additional study of B-cell suppression is warranted.
I型膜增生性肾小球肾炎(MPGN)是一种免疫复合物疾病,预后相对较差。在成人中尚无既定的治疗方法。我们的假设是,这种疾病会对利妥昔单抗(一种抗CD20单克隆抗体)导致的B细胞耗竭产生反应。
我们在加拿大和美国对6例I型MPGN成年患者(4例特发性,2例伴有冷球蛋白血症)进行了一项利妥昔单抗的开放标签试验。利妥昔单抗剂量为第1天和第15天静脉注射1000mg。对患者随访1年。主要结局是蛋白尿的变化。
所有患者在使用利妥昔单抗后外周血B细胞均受到抑制。治疗前平均尿蛋白排泄量为3.9±2.0g/天。在使用利妥昔单抗后,所有患者在所有时间点的蛋白尿均下降。在6、9和12个月时差异有统计学意义(p<0.05),但在3个月时无差异。9个月时最低平均尿蛋白排泄量为1.4±1.4g/天。6例患者中有2例完全缓解,3例部分缓解。在研究过程中肌酐清除率无显著变化。无不良反应。
利妥昔单抗可降低I型MPGN患者的蛋白尿。该试验表明B细胞可能在这种疾病中起作用,有必要对B细胞抑制进行进一步研究。