Tran Cheryl L, Sethi Sanjeev, Murray David, Cramer Carl H, Sas David J, Willrich Maria, Smith Richard J, Fervenza Fernando C
Department of Pediatrics, Division of Pediatric Nephrology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Pediatr Nephrol. 2016 Apr;31(4):683-7. doi: 10.1007/s00467-015-3306-0. Epub 2016 Jan 13.
Dense deposit disease (DDD) is a rare glomerular disease caused by an uncontrolled activation of the alternative complement pathway leading to end-stage renal disease in 50 % of patients. As such, DDD has been classified within the spectrum of complement component 3 (C3) glomerulopathies due to its pathogenesis from alternative pathway dysregulation. Conventional immunosuppressive therapies have no proven effectiveness. Eculizumab, a terminal complement inhibitor, has been reported to mitigate disease in some cases.
CASE-DIAGNOSIS/TREATMENT: We report on the efficacy of eculizumab in a pediatric patient who failed to respond to cyclophosphamide, corticosteroids, and plasma exchange. Complement biomarker profiling was remarkable for low serum C3, low properdin, and elevated soluble C5b-9. Consistent with these findings, the alternative pathway functional assay was abnormally low, indicative of alternative pathway activity, although neither C3-nephritic factors nor Factor H autoantibodies were detected. Eculizumab therapy was associated with significant improvement in proteinuria and renal function allowing discontinuation of hemodialysis (HD). Repeat C3 and soluble C5b-9 levels normalized, showing that terminal complement pathway activity was successfully blocked while the patient was receiving eculizumab therapy. Repeat testing for alternative pathway activation allowed for a successful decrease in eculizumab dosing.
The case reported here demonstrates the successful recovery of renal function in a pediatric patient on HD following the use of eculizumab.
致密物沉积病(DDD)是一种罕见的肾小球疾病,由替代补体途径的失控激活引起,50%的患者会发展为终末期肾病。因此,由于其发病机制是替代途径失调,DDD已被归类于补体成分3(C3)肾小球病范畴。传统免疫抑制疗法尚无经证实的疗效。据报道,终末补体抑制剂依库珠单抗在某些病例中可缓解病情。
病例诊断/治疗:我们报告了依库珠单抗对一名对环磷酰胺、皮质类固醇和血浆置换无反应的儿科患者的疗效。补体生物标志物分析显示血清C3低、备解素低以及可溶性C5b-9升高。与这些发现一致,替代途径功能测定异常低,表明存在替代途径活性,尽管未检测到C3肾炎因子或H因子自身抗体。依库珠单抗治疗使蛋白尿和肾功能显著改善,患者得以停止血液透析(HD)。重复检测显示C3和可溶性C5b-9水平恢复正常,表明在患者接受依库珠单抗治疗期间终末补体途径活性被成功阻断。重复检测替代途径激活情况后成功减少了依库珠单抗的剂量。
本文报道的病例表明,使用依库珠单抗后,一名接受HD治疗的儿科患者的肾功能成功恢复。