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C3 glomerulopathies: Dense deposit disease and C3 glomerulonephritis

Authors
Tal Kopel, MD
David J Salant, MD
Section Editors
Richard J Glassock, MD, MACP
Fernando C Fervenza, MD, PhD
Deputy Editor
Albert Q Lam, MD

INTRODUCTION

Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are rare forms of glomerulonephritis that affect both children and young adults. Both diseases result from abnormal regulation of the alternative complement pathway and are now classified under the heading of "C3 glomerulopathies." The clinical presentation is variable, and the diagnosis is made by immunofluorescence examination of a kidney biopsy specimen, supplemented by studies of the complement system. Whenever possible, the pathogenic mechanism should be identified, as this can help guide therapy.

The pathogenesis, clinical presentation, diagnosis, and treatment of the C3 glomerulopathies (DDD and C3GN) are discussed in this topic. C4 glomerulopathies, as well as general discussions of the differential diagnosis of glomerular disease and the classification of membranoproliferative glomerulonephritis, are presented elsewhere. (See "C4 glomerulopathy" and "Differential diagnosis and evaluation of glomerular disease" and "Clinical presentation, classification, and causes of membranoproliferative glomerulonephritis".)

CLASSIFICATION OF C3 GLOMERULOPATHIES

The C3 glomerulopathies are rare; for example, dense deposit disease (DDD) is estimated to affect only two to three people per one million [1]. Historically, DDD was classified as a subgroup of primary membranoproliferative glomerulonephritis (MPGN type II), but it is now reclassified as a complement-mediated glomerular disease [1-4]. C3 glomerulonephritis (C3GN) was first described in 2007 in a clinicopathologic and genetic study of 19 patients [5]. Subsequently, the term "C3 glomerulopathy" was introduced to encompass all glomerular lesions with predominant C3 accumulation [6,7]. (See "Clinical presentation, classification, and causes of membranoproliferative glomerulonephritis", section on 'Complement-mediated MPGN'.)

The term "dense deposit disease" reflects the characteristic appearance of linear-appearing electron-dense material in the glomerular basement membrane (GBM) observed on kidney biopsy (picture 1).

Like DDD, C3GN is characterized by isolated deposits of C3 on immunofluorescence (picture 2), but instead of dense intramembranous deposits as in DDD (picture 1), electron microscopy reveals subendothelial and mesangial electron-dense deposits (picture 3). In some cases, subepithelial deposits can also be seen.

                                  

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Literature review current through: Nov 2016. | This topic last updated: Tue Nov 08 00:00:00 GMT+00:00 2016.
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