Published online Sep 6, 2015. doi: 10.5527/wjn.v4.i4.455
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.
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.