Eculizumab in Pediatric Dense Deposit Disease

Oosterveld MJS, Garrelfs MR, Hoppe B, Florquin S, Roelofs JJTH, Van Den Heuvel LP, Amann KU, Davin JC, Bouts AHM, Schriemer PJ, Groothoff JW (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Clinical Journal of the American Society of Nephrology American Society of Nephrology

Book Volume: 10

Pages Range: 1773-82

Journal Issue: 10

DOI: 10.2215/CJN.01360215

Abstract

Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease affecting mostly children. Treatment options are limited. Debate exists whether eculizumab, a monoclonal antibody against complement factor C5, is effective in DDD. Reported data are scarce, especially in children.The authors analyzed clinical and histologic data of five pediatric patients with a native kidney biopsy diagnosis of DDD. Patients received eculizumab as therapy of last resort for severe nephritic or nephrotic syndrome with alternative pathway complement activation; this therapy was given only when the patients had not or only marginally responded to immunosuppressive therapy. Outcome measures were kidney function, proteinuria, and urine analysis.In all, seven disease episodes were treated with eculizumab (six episodes of severe nephritic syndrome [two of which required dialysis] and one nephrotic syndrome episode). Median age at treatment start was 8.4 (range, 5.9-13) years. For three treatment episodes, eculizumab was the sole immunosuppressive treatment. In all patients, both proteinuria and renal function improved significantly within 12 weeks of treatment (median urinary protein-to-creatinine ratio of 8.5 [range, 2.2-17] versus 1.1 [range, 0.2-2.0] g/g, P<0.005, and eGFR of 58 [range, 17-114] versus 77 [range, 50-129] ml/min per 1.73 m(2), P<0.01). A striking finding was the disappearance of leukocyturia within 1 week after the first eculizumab dose in all five episodes with leukocyturia at treatment initiation.In this case series of pediatric patients with DDD, eculizumab treatment was associated with reduction in proteinuria and increase in eGFR. Leukocyturia resolved within 1 week of initiation of eculizumab treatment. These results underscore the need for a randomized trial of eculizumab in DDD.

Authors with CRIS profile

Kerstin Ute Amann Department of Nephropathology

Involved external institutions

Academic Medical Centre / Academisch Medisch Centrum (AMC) NL Netherlands (NL) Radboud University Nijmegen NL Netherlands (NL) University of Amsterdam NL Netherlands (NL) Universitätsklinikum Bonn DE Germany (DE)

How to cite

APA:

Oosterveld, M.J.S., Garrelfs, M.R., Hoppe, B., Florquin, S., Roelofs, J.J.T.H., Van Den Heuvel, L.P.,... Groothoff, J.W. (2015). Eculizumab in Pediatric Dense Deposit Disease. Clinical Journal of the American Society of Nephrology, 10(10), 1773-82. https://doi.org/10.2215/CJN.01360215

MLA:

Oosterveld, Michiel J. S., et al. "Eculizumab in Pediatric Dense Deposit Disease." Clinical Journal of the American Society of Nephrology 10.10 (2015): 1773-82.

BibTeX: Download