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

Cheryl L. Tran, Sanjeev M Sethi, David Murray, Carl H. Cramer, David Sas, Maria Willrich, Richard J. Smith, Fernando Custodio Fervenza

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)683-687
Number of pages5
JournalPediatric Nephrology
Volume31
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

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

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health

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