Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. May 6, 2015; 4(2): 169-184
Published online May 6, 2015. doi: 10.5527/wjn.v4.i2.169
Complement involvement in kidney diseases: From physiopathology to therapeutical targeting
Maurizio Salvadori, Giuseppina Rosso, Elisabetta Bertoni
Maurizio Salvadori, Elisabetta Bertoni, 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; Bertoni E edited the manuscript; all authors wrote and approved the final draft.
Conflict-of-interest: 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: +39-55-597151
Received: August 28, 2014
Peer-review started: August 30, 2014
First decision: December 2, 2014
Revised: December 22, 2014
Accepted: January 15, 2015
Article in press: January 19, 2015
Published online: May 6, 2015
Abstract

Complement cascade is involved in several renal diseases and in renal transplantation. The different components of the complement cascade might represent an optimal target for innovative therapies. In the first section of the paper the authors review the physiopathology of complement involvement in renal diseases and transplantation. In some cases this led to a reclassification of renal diseases moving from a histopathological to a physiopathological classification. The principal issues afforded are: renal diseases with complement over activation, renal diseases with complement dysregulation, progression of renal diseases and renal transplantation. In the second section the authors discuss the several complement components that could represent a therapeutic target. Even if only the anti C5 monoclonal antibody is on the market, many targets as C1, C3, C5a and C5aR are the object of national or international trials. In addition, many molecules proved to be effective in vitro or in preclinical trials and are waiting to move to human trials in the future.

Keywords: Complement cascade, Complement and glomerulopathies, Eculizumab, Targeting complement, Complement and renal transplantation

Core tip: Our therapeutical armamentarium is to date limited in many kidney diseases and in several aspects of renal transplantation. The findings that complement cascade is involved in many kidney diseases and in renal transplantation offer the availability of new therapeutical targets basing on the pathogenesis. The anti C5 monoclonal antibody, eculizumab, is now used to treat the atypical hemolytic uremic syndrome (aHUS), but 24 trials are ongoing in different renal diseases and in renal transplantation. Other targets as C1, C3, C5a, and C5aR are innovative treatments for diseases as aHUS, membranoproliferative glomerulonephritis, ischemia-reperfusion injury, and objects of ongoing trials.