Guzman German Lozano, Perry Katherine W
Phoenix Children's Hospital-Thomas Campus, Phoenix, Arizona, USA.
Nephrology (Carlton). 2025 Feb;30(2):e70001. doi: 10.1111/nep.70001.
Complement 3 glomerulonephritis (C3GN) is a rare glomerular disease involving dysregulation of the complement system. We describe our experience using pegcetacoplan, an inhibitor of C3 and its activation fragment, C3b, for treatment-resistant C3GN in a 9-year-old boy referred for evaluation of refractory membranoproliferative glomerulonephritis. Despite treatment with intense immunosuppression (high-dose steroids, mycophenolate mofetil and calcineurin inhibitor), he continued to have high disease activity with low C3 levels (35 mg/dL), hypertension, symptomatic oedema, anaemia, and nephrotic-range proteinuria (e.g., urine protein-to-creatinine ratio [uPCR], 10 g/g; serum creatinine, 0.4 mg/dL). Given the concern for refractory C3GN following a steroid taper and tacrolimus trial with modest response (reduced proteinuria), we initiated pegcetacoplan 540 mg twice weekly for 1 week, followed by 648 mg twice weekly. Laboratory values before pegcetacoplan initiation included uPCR, 1.1 g/g, serum creatinine, 0.87 mg/dL, serum albumin, 4.7 g/dL, and serum C3, 30 mg/dL. Clinically significant improvements in serum C3 (142 mg/dL) and uPCR (422 mg/g) were observed within 1 week of pegcetacoplan initiation; within 3 months (uPCR, 322 mg/g; serum creatinine, 0.69 mg/dL; serum C3, 297 mg/dL), all immunosuppressive and antihypertensive medications were discontinued. No adverse effects of pegcetacoplan were reported. A kidney biopsy after 6 months of pegcetacoplan treatment showed mesangial and focal endocapillary proliferative glomerulonephritis with isolated C3c deposition by immunofluorescence, consistent with previous C3GN diagnosis. In this paediatric patient, compassionate use of pegcetacoplan was associated with rapid clinical improvement without adverse effects, and clinical effectiveness was confirmed by laboratory and histologic results within 6 months of treatment initiation.
补体3肾小球肾炎（C3GN）是一种罕见的肾小球疾病，涉及补体系统失调。我们描述了我们使用培克西普单抗（一种C3及其活化片段C3b的抑制剂）治疗一名9岁男孩难治性C3GN的经验，该男孩因难治性膜增生性肾小球肾炎转诊进行评估。尽管接受了强化免疫抑制治疗（高剂量类固醇、霉酚酸酯和钙调神经磷酸酶抑制剂），但他的疾病活动度仍然很高，C3水平较低（35mg/dL），伴有高血压、症状性水肿、贫血和肾病范围蛋白尿（例如，尿蛋白与肌酐比值[uPCR]为10g/g；血清肌酐为0.4mg/dL）。考虑到在类固醇减量和他克莫司试验反应适中（蛋白尿减少）后出现难治性C3GN，我们开始每周两次给予培克西普单抗540mg，持续1周，随后每周两次给予648mg。开始使用培克西普单抗前的实验室检查值包括uPCR为1.1g/g、血清肌酐为0.87mg/dL、血清白蛋白为4.7g/dL、血清C3为30mg/dL。在开始使用培克西普单抗的1周内，观察到血清C3（142mg/dL）和uPCR（422mg/g）有临床显著改善；在3个月内（uPCR为322mg/g；血清肌酐为0.69mg/dL；血清C3为297mg/dL），所有免疫抑制和抗高血压药物均停用。未报告培克西普单抗的不良反应。培克西普单抗治疗6个月后的肾活检显示系膜和局灶性毛细血管内增生性肾小球肾炎，免疫荧光显示孤立的C3c沉积，与先前的C3GN诊断一致。在这名儿科患者中，同情用药使用培克西普单抗与临床快速改善且无不良反应相关，并且在开始治疗的6个月内通过实验室和组织学结果证实了临床有效性。
