Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Jan 6, 2018; 7(1): 29-40
Published online Jan 6, 2018. doi: 10.5527/wjn.v7.i1.29
Immunoglobulin G4-related kidney diseases: An updated review
Maurizio Salvadori, Aris Tsalouchos
Maurizio Salvadori, Renal Unit, Department of Transplantation, Careggi University Hospital, Florence 50139, Italy
Aris Tsalouchos, Division of Nephrology, Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
Author contributions: Salvadori M and Tsalouchos A contributed equally to the manuscript; Salvadori M designed the study, performed the last revision and provided answers to the reviewers; Tsalouchos A collected the data from literature; Salvadori M and Tsalouchos A analyzed the collected data and wrote the manuscript.
Conflict-of-interest statement: The authors do not have any conflict of interest in relation to the manuscript, as in the attached form.
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, Renal Unit, Department of Transplantation, Careggi University Hospital, viale Pieraccini 18, Florence 50139, Italy. maurizio.salvadori1@gmail.com
Telephone: +39-55-597151 Fax: +39-55-597151
Received: November 6, 2017
Peer-review started: November 9, 2017
First decision: December 1, 2017
Revised: December 15, 2017
Accepted: December 28, 2017
Article in press: December 28, 2017
Published online: January 6, 2018
Processing time: 62 Days and 9.8 Hours
Abstract

This review will encompass definition, pathogenesis, renal clinical manifestations and treatment of immunoglobulin G4-related diseases (IgG4-RDs). IgG4-RD is a recently recognized clinical entity that often involves multiple organs and is characterized by high levels of serum immunoglobulins G4, dense infiltration of IgG4+ cells and storiform fibrosis. Cellular immunity, particularly T-cell mediated immunity, has been implicated in the pathogenesis of IgG4-RDs. The most frequent renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis, membranous glomerulopathy and obstructive nephropathy secondary to urinary tract obstruction due to IgG4-related retroperitoneal fibrosis. IgG4-RD diagnosis should be based on specific histopathological findings, confirmed by tissue immunostaining, typical radiological findings and an appropriate clinical context. The first line treatment is the steroids with two warnings: Steroid resistance and relapse after discontinuation. In the case of steroid resistance, B cell depleting agents as rituximab represent the second-line treatment. In the case of relapse after discontinuation, steroid treatment may be associated with steroid sparing agents. Since the disease has been only recently identified, more prospective, long-term studies are needed to an improved understanding and a more correct and safe treatment.

Keywords: Immunoglobulin G4-related disease; Storiform fibrosis; Lymphoplasmacytic infiltration; Tubulointerstitial nephritis; Steroid treatment; B cell depleting agents

Core tip: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized clinical entity that often involves multiple organs; it is characterized by high levels of serum immunoglobulin G4, dense infiltration of IgG4+ cells, and storiform fibrosis. Cellular immunity, particularly T cell-mediated immunity, has been implicated in the pathogenesis of IgG4-RD. The most frequent renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis, membranous glomerulonephropathy and obstructive nephropathy secondary to urinary tract obstruction due to IgG4-related retroperitoneal fibrosis. In IgG4-membranous glomerulopathy, proteinuria can be in the nephrotic range. Steroid treatment is the first-line therapy. For relapsing or refractory cases, immunosuppressants could be combined with steroids.