Klaus Richard, Kanzelmeyer Nele, Haffner Dieter, Lange-Sperandio Bärbel
Department of Pediatrics, Dr. v. Hauner Children's Hospital, LMU University Hospital, LMU Munich, Munich, Germany.
Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.
Pediatr Nephrol. 2025 Feb;40(2):423-430. doi: 10.1007/s00467-024-06512-4. Epub 2024 Sep 25.
Anti-GBM disease is a rare vasculitis mediated by pathogenic antibodies against collagen IV. Anti-GBM disease presents with rapid progressive glomerulonephritis and leads to kidney failure if untreated. KDIGO recommends plasma exchanges (PEX) for antibody elimination and steroids plus cyclophosphamide (CTX) to suppress antibody production. CTX is associated with severe side effects including gonadal toxicity. Rituximab (RTX) and mycophenolate mofetil (MMF) might be a less toxic but equally efficient alternative to CTX. Studies in pediatric anti-GBM disease patients receiving RTX and MMF instead of CTX are lacking.
A retrospective survey in 8 tertiary German centers was performed. The clinical data of patients diagnosed between 2014 and 2022 were collected and analyzed.
Five adolescent patients treated with PEX and RTX and/or MMF due to anti-GBM disease were analyzed. All patients had anti-GBM antibodies, hematuria, glomerular proteinuria, and pulmonary hemorrhage. eGFR was 124 ml/min/1.73 m (range 47-162), and all patients were non-dialysis-dependent but with relevant histological kidney affection (mean crescents on kidney biopsy 77%). Antibody clearance was achieved after 13 PEX cycles (range 6-31). Four out of 5 patients received methylprednisolone pulses. All patients received oral prednisolone and MMF, and four patients received a median of 4 RTX doses (range 2-4). After a mean follow-up of 27 months, 4/5 patients had conserved or improved kidney function, while one patient (20%) developed kidney failure.
In this small series of pediatric non-dialysis-dependent anti-GBM disease patients, first-line treatment with RTX and MMF showed a favorable kidney outcome in 4/5 cases and had an acceptable side effect profile.
抗肾小球基底膜（GBM）病是一种罕见的血管炎，由针对IV型胶原的致病性抗体介导。抗GBM病表现为快速进展性肾小球肾炎，若不治疗会导致肾衰竭。改善全球肾脏病预后组织（KDIGO）建议进行血浆置换（PEX）以清除抗体，并使用类固醇加环磷酰胺（CTX）来抑制抗体产生。CTX与包括性腺毒性在内的严重副作用相关。利妥昔单抗（RTX）和霉酚酸酯（MMF）可能是毒性较小但同样有效的CTX替代药物。目前缺乏针对接受RTX和MMF而非CTX治疗的儿童抗GBM病患者的研究。
对德国8个三级医疗中心进行了一项回顾性调查。收集并分析了2014年至2022年期间确诊患者的临床数据。
分析了5例因抗GBM病接受PEX和RTX和/或MMF治疗的青少年患者。所有患者均有抗GBM抗体、血尿、肾小球性蛋白尿和肺出血。估算肾小球滤过率（eGFR）为124 ml/min/1.73 m²（范围47 - 162），所有患者均无需透析，但存在相关的肾脏组织学病变（肾活检平均新月体形成率77%）。在进行13次PEX循环（范围6 - 31）后实现了抗体清除。5例患者中有4例接受了甲泼尼龙冲击治疗。所有患者均接受口服泼尼松龙和MMF，4例患者接受了中位数为4剂的RTX（范围2 - 4）。平均随访27个月后，5例患者中有4例肾功能得以保留或改善，而1例患者（20%）发展为肾衰竭。
在这一小系列无需透析的儿童抗GBM病患者中，RTX和MMF一线治疗在4/5的病例中显示出良好的肾脏预后，且副作用可接受。
