Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Jul 6, 2016; 5(4): 308-320
Published online Jul 6, 2016. doi: 10.5527/wjn.v5.i4.308
Reclassification of membranoproliferative glomerulonephritis: Identification of a new GN: C3GN
Maurizio Salvadori, Giuseppina Rosso
Maurizio Salvadori, Department of Renal Transplantation, Careggi University Hospital, 50139 Florence, Italy
Giuseppina Rosso, Division of Nephrology, San Luca Hospital, 55100 Lucca, Italy
Author contributions: Salvadori M coordinated the study; Rosso G reviewed the literature; Salvadori M and Rosso G edited the manuscript.
Conflict-of-interest statement: The authors declare to have no conflict of interest in relation to the present manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Maurizio Salvadori, MD, Department of Renal Transplantation, Careggi University Hospital, viale Pieraccini 18, 50139 Florence, Italy. maurizio.salvadori1@gmail.com
Telephone: +39-055-597151 Fax: +39-055-597151
Received: March 7, 2016
Peer-review started: March 9, 2016
First decision: March 25, 2016
Revised: March 31, 2016
Accepted: May 17, 2016
Article in press: May 27, 2016
Published online: July 6, 2016
Processing time: 114 Days and 8.6 Hours
Abstract

This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies.

Keywords: Glomerulonephritis reclassification; Dense deposit disease; Membranoproliferative glomerulonephritis; C3 glomerulopathies; Targeting complement pathways; Complement dysregulation

Core tip: The complement pathway dysregulation has been recognized as the main cause of some membranoproliferative glomerulonephritis (MPGNs). This fact is at the basis of the new classification of the disease and of the findings of new entities as the complement factor H related protein nephropathy. Genetic studies as well as improvement in proteomics allowed recognizing the complement dysregulation as the cause of some renal diseases as the MPGN and the atypical hemolytic uremic syndrome that may be considered as strictly related diseases. The anti-complement drugs represent a new approach in the treatment of these diseases and their use in larger evidence based randomized trials is required.