Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Sep 6, 2015; 4(4): 455-467
Published online Sep 6, 2015. doi: 10.5527/wjn.v4.i4.455
Update on immunoglobulin A nephropathy, Part I: Pathophysiology
Maurizio Salvadori, Giuseppina Rosso
Maurizio Salvadori, Department of Transplantation and Renal Diseases, Careggi University Hospital, 50139 Florence, Italy
Giuseppina Rosso, Division of Nephrology, San Luca Hospital, 55100 Lucca, Italy
Author contributions: Salvadori M and Rosso G both contributed to this paper.
Conflict-of-interest statement: No conflict of interest is declared by any of the authors.
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:
Correspondence to: Maurizio Salvadori, Medical Doctor, Department of Transplantation and Renal Diseases, Careggi University Hospital, viale Pieraccini 18, 50139 Florence, Italy.
Telephone: +39-055-597151 Fax: +39-055-597151
Received: June 23, 2015
Peer-review started: June 23, 2015
First decision: August 4, 2015
Revised: August 24, 2015
Accepted: August 30, 2015
Article in press: August 31, 2015
Published online: September 6, 2015

Immunoglobulin A (IgA) nephropathy is one of the most common glomerulonephritis and its frequency is probably underestimated because in most patients the disease has an indolent course and the kidney biopsy is essential for the diagnosis. In the last years its pathogenesis has been better identified even if still now several questions remain to be answered. The genetic wide association studies have allowed to identifying the relevance of genetics and several putative genes have been identified. The genetics has also allowed explaining why some ancestral groups are affected with higher frequency. To date is clear that IgA nephropathy is related to auto antibodies against immunoglobulin A1 (IgA1) with poor O-glycosylation. The role of mucosal infections is confirmed, but which are the pathogens involved and which is the role of Toll-like receptor polymorphism is less clear. Similarly to date whether the disease is due to the circulating immunocomplexes deposition on the mesangium or whether the antigen is already present on the mesangial cell as a “lanthanic” deposition remains to be clarified. Finally also the link between the mesangial and the podocyte injury and the tubulointerstitial scarring, as well as the mechanisms involved need to be better clarified.

Keywords: Immunoglobulin A, Immunoglobulin A galactosylation, Genome-wide association studies, Auto antibodies, Complement in renal diseases, Mesangial linked growth factors

Core tip: For few glomerular diseases a new pathogenetic pathway has been recognized in the recent years as happened for the immunoglobulin A (IgA) nephropathy. Finding in the genetics allowed identifying several loci putative for the disease progression. Spectrometry mass studies and 3 dimension studies have allowed bettering clarifying the molecules involved at glomerular level. Molecular studies of the mesangium allowed identifying new receptors responsible for the IgA immune complexes deposition and for the binding to the mesangial structure. Finally molecular and cellular studies opened new ways to understanding the link and the cross-talk between the glomeruli and the tubulointerstitial structure.