Wéclawiak Hugo, Ribes David, Modesto Anne, Kamar Nassim, Durand Dominique, Rostaing Lionel
Départment de néphrologie, dialyse et transplantation d'organes, CHU de Rangueil, 1, avenue Jean-Poulhes, TSA 50032 Toulouse cedex 09, France.
Nephrol Ther. 2007 Apr;3(2):65-8. doi: 10.1016/j.nephro.2007.02.004. Epub 2007 Apr 6.
Idiopathic membranous glomerulonephritis (MGN) is a rare cause of end-stage renal failure, which can lead to chronic hemodialysis. This glomerulopathy can recur after renal transplantation despite immunosuppressive therapy. To date, there is no confirmed therapy for treatment of renal grafts after recurrence of MGN. Herein, we report on a 27-year-old man who underwent cadaveric renal transplantation for MGN in September 2001. At 2 months posttransplant, a renal biopsy showed membranous deposition on immunofluorescence staining evocative of recurrence of MGN. Proteinuria developed progressively and, at one year, was estimated at 7.65 g/24 h, with hypoalbuminemia of 24 g/l. This persisted despite symptomatic treatment with anti-proteinuric agents (enalapril 20 mg/day and irbesartan 75 mg/day) and atorvastatin (10 mg/day). By March 2004, his proteinuria was 11 g/day; therefore, therapy with rituximab (monoclonal anti-CD20) at 375 mg/m(2) weekly was initiated for four consecutive weeks, followed by the same dosage every four months for one year. Biological controls performed two weeks after the fourth infusion of rituximab showed a fall in proteinuria, assessed at 1 g/24 h, with albuminemia of 29 g/l and normalized lipidic results. A renal biopsy performed 6 months after the first infusion was unchanged. Follow-up at 30 months showed consistent remission of membranous nephropathy, demonstrated by a serum creatinine level of 150 mumol/L, microalbuminuria of 107 mg/24 h and normal albuminemia of 43.7 g/l. There were no side effects; in particular, no infectious complications occurred, despite CD19 lymphocytes being still negative after 30 months. Monoclonal CD-20 antibodies have shown efficacy against MGN compared to conventional therapies in native kidneys. It has recently been shown that CD20 mRNA is overexpressed in the renal interstitium in patients suffering from MGN and that the interstitial infiltrates is mainly composed of B-cell lymphocytes in these patients. These data may explain the efficiency of rituximab in these circumstances.
特发性膜性肾小球肾炎(MGN)是终末期肾衰竭的罕见病因,可导致慢性血液透析。尽管进行了免疫抑制治疗,但这种肾小球病在肾移植后仍可能复发。迄今为止,对于MGN复发后肾移植的治疗尚无确切疗法。在此,我们报告一名27岁男性,他于2001年9月因MGN接受了尸体肾移植。移植后2个月,肾活检免疫荧光染色显示膜性沉积,提示MGN复发。蛋白尿逐渐加重,1年后估计为7.65 g/24小时,伴有低白蛋白血症,白蛋白水平为24 g/L。尽管使用抗蛋白尿药物(依那普利20 mg/天和厄贝沙坦75 mg/天)和阿托伐他汀(10 mg/天)进行了对症治疗,但蛋白尿仍持续存在。到2004年3月,他的蛋白尿为11 g/天;因此,开始每周一次静脉注射利妥昔单抗(抗CD20单克隆抗体),剂量为375 mg/m²,连续四周,随后每四个月给予相同剂量,持续一年。在第四次输注利妥昔单抗两周后进行的生物学检查显示蛋白尿下降,评估为1 g/24小时,白蛋白血症为29 g/L,血脂结果正常。第一次输注后6个月进行的肾活检结果无变化。30个月的随访显示膜性肾病持续缓解,血清肌酐水平为150 μmol/L,微量白蛋白尿为107 mg/24小时,白蛋白血症正常,为43.7 g/L。未出现副作用;特别是,尽管30个月后CD19淋巴细胞仍为阴性,但未发生感染并发症。与传统疗法相比,抗CD20单克隆抗体已显示出对天然肾脏MGN的疗效。最近研究表明,MGN患者肾间质中CD20 mRNA过度表达,且这些患者的间质浸润主要由B淋巴细胞组成。这些数据可能解释了利妥昔单抗在这种情况下的疗效。