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

7 Citations (Scopus)

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

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Membranoproliferative Glomerulonephritis
Dialysis
Pediatrics
Complement Membrane Attack Complex
Complement Inactivating Agents
Kidney
Renal Dialysis
Therapeutics
Properdin
Alternative Complement Pathway
Complement Factor H
Complement C3
Plasma Exchange
Recovery of Function
Immunosuppressive Agents
Rare Diseases
Proteinuria
Autoantibodies
Cyclophosphamide
Chronic Kidney Failure

Keywords

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

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health

Cite this

Discontinuation of dialysis with eculizumab therapy in a pediatric patient with dense deposit disease. / Tran, Cheryl L.; Sethi, Sanjeev M; Murray, David; Cramer, Carl H.; Sas, David; Willrich, Maria; Smith, Richard J.; Fervenza, Fernando Custodio.

In: Pediatric Nephrology, Vol. 31, No. 4, 01.04.2016, p. 683-687.

Research output: Contribution to journalArticle

Tran, Cheryl L. ; Sethi, Sanjeev M ; Murray, David ; Cramer, Carl H. ; Sas, David ; Willrich, Maria ; Smith, Richard J. ; Fervenza, Fernando Custodio. / Discontinuation of dialysis with eculizumab therapy in a pediatric patient with dense deposit disease. In: Pediatric Nephrology. 2016 ; Vol. 31, No. 4. pp. 683-687.
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