Treatment-resistant nephrotic syndrome in dense deposit disease: complement-mediated glomerular capillary wall injury?
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Published:2020-05-23
Issue:9
Volume:35
Page:1791-1795
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ISSN:0931-041X
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Container-title:Pediatric Nephrology
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language:en
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Short-container-title:Pediatr Nephrol
Author:
Duineveld Caroline,Steenbergen Eric J.,Bomback Andrew S.,van de Kar Nicole C. A. J.,Wetzels Jack F. M.
Abstract
Abstract
Background
The C3 glomerulopathies (C3G) are recently defined glomerular diseases, attributed to abnormal complement regulation. Dense deposit disease (DDD) is part of the spectrum of C3G, characterized by electron-dense deposits in the lamina densa of the glomerular basement membrane. Patients with DDD present with hematuria, variable degrees of proteinuria, and kidney dysfunction. Kidney biopsies typically disclose proliferative and inflammatory patterns of injury. Treatment with glucocorticoids and mycophenolate mofetil has been shown to achieve remission of proteinuria in a significant proportion of C3G patients.
Case-diagnosis/treatment
We report two patients with persistent nephrotic syndrome while on immunosuppressive therapy. Repeat kidney biopsies disclosed massive C3 deposits with foot process effacement in the absence of proliferative or inflammatory lesions on light microscopy.
Conclusion
These cases, coupled with data from animal models of disease and the variable response to eculizumab in C3G patients, illustrate that two different pathways might be involved in the development of kidney injury in C3G: a C5-independent pathway leading to glomerular capillary wall injury and the development of proteinuria versus a C5-dependent pathway that causes proliferative glomerulonephritis and kidney dysfunction.
Funder
Radboud University Medical Center
Publisher
Springer Science and Business Media LLC
Subject
Nephrology,Pediatrics, Perinatology, and Child Health
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