Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. May 6, 2018; 7(3): 71-83
Published online May 6, 2018. doi: 10.5527/wjn.v7.i3.71
Antineutrophil cytoplasmic antibody associated vasculitides with renal involvement: Open challenges in the remission induction therapy
Maurizio Salvadori, Aris Tsalouchos
Maurizio Salvadori, Department of Nephrology and Renal Transplantation, Careggi University Hospital, Florence 50139, Italy
Aris Tsalouchos, Department of Nephrology and Dialysis, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
Author contributions: Salvadori M and Tsalouchos A equally contributed to the manuscript.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
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, Professor, Department of Nephrology and Renal Transplantation, Careggi University Hospital, Viale Gaetano Pieraccini, 18, Florence 50139, Italy. maurizio.salvadori1@gmail.com
Telephone: +39-55-597151 Fax: +39-55-597151
Received: February 2, 2018
Peer-review started: February 5, 2018
First decision: March 7, 2018
Revised: March 12, 2018
Accepted: April 18, 2018
Article in press: April 22, 2018
Published online: May 6, 2018
Processing time: 93 Days and 11.1 Hours
Abstract

Renal involvement with rapidly progressive glomerulonephritis is a common manifestation of antineutrophil cytoplasmic antibody (ANCA) associated vasculitides, which is characterized by end-stage renal disease and high mortality rates in untreated and/or late referral patients. The long-term renal survival has improved dramatically since the addition of cyclophosphamide (CYC) and recently of rituximab (RTX) in association with corticosteroids in the remission induction therapeutic regimens. However, renal prognosis remains unfavorable for many patients and the mortality rate is still significantly high. In this review, we analyze the open challenges to be addressed to optimize the induction remission therapy, principally in patients with advanced kidney failure. This concern the first-line therapy (CYC or RTX) based on different parameters (estimated glomerular filtration rate at baseline, new or relapsed disease, ANCA specificity, tissue injury, safety), the role of plasma exchange and the role of new therapies. Indeed, we discuss future perspectives in induction remission therapy by reporting recent advances in new targeted therapies with particular reference to avacopan, an orally administered selective C5a receptor inhibitor.

Keywords: Rapidly progressive glomerulonephritis; Remission induction therapy; Antineutrophil cytoplasmic antibody associated vasculitides; Cyclophosphamide; Rituximab; Corticosteroids; Plasma exchange; Avacopan

Core tip: Antineutrophil cytoplasmic antibody (ANCA) associated vasculitides with renal involvement, presents as Rapidly Progressive Glomerulonephritis are organ-threatening and potentially life-threatening diseases. Although remission induction immunosuppressive regimens overall have been very successful in the treatment of these conditions, many questions remain unanswered. The still open challenges and questions concern: (1) The choice of the first-line therapy (cyclophosphamide versus rituximab) based on renal function at baseline, new versus relapsed disease, ANCA specificity, tissue injury and safety; (2) the role of plasma exchange in combination with steroid and non steroid agents; and (3) the advent of novel target therapies and strategies.