A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient's nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 μmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5➝147 μmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 μmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.
患者男性，31岁。因水肿、蛋白尿2年余就诊，外院肾脏病理提示不典型膜性肾病。糖皮质激素联合钙调磷酸酶抑制剂、4程利妥昔单抗（1 g，静脉输注）治疗后肾病综合征无缓解，24 h尿蛋白仍高达31.18 g，考虑为难治性肾病综合征。后期病程中短期内出现肌酐升高（322.5 μmol/L），重复肾组织活检病理示膜性肾病合并急性间质性肾炎，予足量糖皮质激素联合环磷酰胺加第5程利妥昔单抗1 g静脉输注，间质性肾炎导致的肾功能损害呈现缓解趋势（血肌酐322.5 μmol/L➝147 μmol/L），但膜性肾病仍未能部分缓解，随后尝试使用奥妥珠单抗（1 g，静脉输注）。患者门诊规律随诊，末次随访抗磷脂酶A2受体抗体阴性，B细胞清零，血白蛋白36 g/L，尿总蛋白肌酐比4 810 mg/g，血肌酐162 μmol/L。提示奥妥珠单抗在难治性膜性肾病中的疗效。此外，在肾病综合征的任何时期，合并急性肾损伤时均需要鉴别原因，寻找可逆因素并行针对性治疗，尽可能延缓肾功能恶化。.