Discontinuation of dialysis with eculizumab therapy in a pediatric patient with dense deposit disease

作者：Tran Cheryl L^*; Sethi Sanjeev; Murray David; Cramer Carl H; Sas David J; Willrich Maria; Smith Richard J; Fervenza Fernando C

来源：Pediatric Nephrology, 2016, 31(4): 683-687.

DOI：10.1007/s00467-015-3306-0

• Dense deposit disease
• Soluble C5b-9
• Alternative complement pathway
• Eculizumab
• Hemodialysis

Background 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.
Conclusions The case reported here demonstrates the successful recovery of renal function in a pediatric patient on HD following the use of eculizumab.

• 出版日期2016-4