Busch Martin, Gerth Jens, Ott Undine, Schip Andre, Haufe Christoph C, Gröne Hermann-Josef, Wolf Gunter
Klinik für Innere Medizin III, Klinikum der Friedrich-Schiller-Universität Jena, Jena.
Med Klin (Munich). 2008 Jul 15;103(7):519-24. doi: 10.1007/s00063-008-1077-0.
Membranous nephropathy (MN) is characterized by proteinuria and other symptoms of the nephrotic syndrome. In many cases, the etiology is unknown. Whether and how to treat MN is still a controversial question. Despite the use of corticosteroids and alkylating agents, up to 40% of patients still progress to end-stage renal failure.
A 40-year-old male patient with biopsy-proven idiopathic MN was initially treated with prednisolone and chlorambucil because of a proteinuria of 22 g/d. Treatment with cyclosporine was started because the nephrotic syndrome failed to improve. Proteinuria was reduced to a minimum of 4 g/d. Cyclosporine was stopped after 17 months leading to a fast relapse. Therapy with an ACE inhibitor and AT(1) receptor antagonist and retreatment with cyclosporine improved proteinuria. Cyclosporine was terminated after a total of 24 months. 5 months later, relapse occurred with a high proteinuria of 34 g/d. The monoclonal anti-CD20 antibody rituximab (375 mg/m(2)) was given four times every 4 weeks. 4 weeks and 4 months after the end of treatment, proteinuria decreased to 780 mg/d and <150 mg/d, but renal function remained impaired (creatinine clearance 65 ml/min, stage 2 according to K/DOQI). Now, remission of proteinuria (<150 mg/d) has been stable for almost 2 years. However, renal insufficiency progressed further (creatinine clearance 45 ml/min, stage 3 according to K/DOQI).
Rituximab offers the possibility for a targeted treatment of idiopathic MN. Based on the existing evidence and experience from this case, rituximab can be recommended as a new treatment option for MN, possibly before starting any treatment with cytotoxic agents and high-dose prednisolone carrying the risk of severe side effects. However, long-term results of this treatment are still lacking.
膜性肾病(MN)的特征为蛋白尿及其他肾病综合征症状。在许多病例中,病因不明。MN是否以及如何治疗仍是一个有争议的问题。尽管使用了皮质类固醇和烷化剂,但仍有高达40%的患者进展至终末期肾衰竭。
一名40岁男性患者,经活检证实为特发性MN,最初因蛋白尿22 g/d接受泼尼松龙和苯丁酸氮芥治疗。由于肾病综合征未改善,开始使用环孢素治疗。蛋白尿降至最低4 g/d。17个月后停用环孢素,导致快速复发。使用血管紧张素转换酶抑制剂和AT(1)受体拮抗剂治疗并再次使用环孢素后,蛋白尿有所改善。共24个月后停用环孢素。5个月后,复发,蛋白尿高达34 g/d。每4周给予单克隆抗CD20抗体利妥昔单抗(375 mg/m²)4次。治疗结束后4周和4个月,蛋白尿分别降至780 mg/d和<150 mg/d,但肾功能仍受损(肌酐清除率65 ml/min,根据K/DOQI为2期)。目前,蛋白尿缓解(<150 mg/d)已稳定近2年。然而,肾功能不全进一步进展(肌酐清除率45 ml/min,根据K/DOQI为3期)。
利妥昔单抗为特发性MN的靶向治疗提供了可能。基于本病例的现有证据和经验,利妥昔单抗可作为MN的一种新治疗选择推荐,可能在开始使用有严重副作用风险的细胞毒性药物和大剂量泼尼松龙治疗之前。然而,该治疗的长期结果仍缺乏。