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

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

doi:10.1007/s00467-015-3306-0

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

Journal article

Peer reviewed

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

Cheryl L Tran, Sanjeev Sethi, David Murray, Carl H Cramer, David J Sas, Maria Willrich, Richard J Smith and Fernando C Fervenza

Pediatric nephrology (Berlin, West), Vol.31(4), pp.683-687

04/2016

DOI: 10.1007/s00467-015-3306-0

PMID: 26759144

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Abstract

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. 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.

Antibodies, Monoclonal, Humanized - therapeutic use

Kidney - drug effects

Kidney - pathology

Complement C3 - metabolism

Complement Membrane Attack Complex - metabolism

Humans

Immunosuppressive Agents - therapeutic use

Kidney - immunology

Treatment Outcome

Glomerulonephritis, Membranoproliferative - blood

Biomarkers - blood

Glomerulonephritis, Membranoproliferative - therapy

Glomerulonephritis, Membranoproliferative - immunology

Biopsy

Adolescent

Female

Glomerulonephritis, Membranoproliferative - diagnosis

Complement Activation - drug effects

Renal Dialysis

Details

Title: Subtitle: Discontinuation of dialysis with eculizumab therapy in a pediatric patient with dense deposit disease
Creators: Cheryl L Tran - Department of Pediatrics, Division of Pediatric Nephrology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. tran.cheryl2@mayo.edu
Sanjeev Sethi - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
David Murray - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Carl H Cramer - Department of Pediatrics, Division of Pediatric Nephrology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
David J Sas - Department of Pediatrics, Division of Pediatric Nephrology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
Maria Willrich - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Richard J Smith - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA, USA
Fernando C Fervenza - Department of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
Resource Type: Journal article
Publication Details: Pediatric nephrology (Berlin, West), Vol.31(4), pp.683-687
DOI: 10.1007/s00467-015-3306-0
PMID: 26759144
NLM abbreviation: Pediatr Nephrol
ISSN: 0931-041X
eISSN: 1432-198X
Publisher: Germany
Language: English
Date published: 04/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006366702771

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