Gut-kidney axis in IgA nephropathy: Role on mesangial cell metabolism and inflammation

Abstract

IgA Nephropathy (IgAN) is the commonest primary glomerular disease around the world and represents a significant cause of end-stage renal disease. IgAN is characterized by mesangial deposition of IgA-immune complexes and mesangial expansion. The pathophysiological process includes an abnormally glycosylated IgA1, which is an antigenic target. Autoantibodies specifically recognize galactose-deficient IgA1 forming immune complexes that are amplified in size by the soluble IgA Fc receptor CD89 leading to deposition in the mesangium through interaction with non-classical IgA receptors. The local production of cytokines promotes local inflammation and complement system activation, besides the stimulation of mesangial proliferation. The spectrum of clinical manifestations is quite variable from asymptomatic microscopic hematuria to rapidly progressive glomerulonephritis. Despite all the advances, the pathophysiology of the disease is still not fully elucidated. The mucosal immune system is quoted to be a factor in triggering IgAN and a “gut-kidney axis” is proposed in its development. Furthermore, many recent studies have demonstrated that food intake interferes directly with disease prognosis. In this review, we will discuss how mucosal immunity, microbiota, and nutritional status could be interfering directly with the activation of intrinsic pathways of the mesangial cells, directly resulting in changes in their function, inflammation and development of IgAN.

Bibliometric analysis of mucosal immunity in IgA nephropathy from 1990 to 2022

“…As for the co‐appearance keywords through Citespace, “mucosal immunity,” “galactose deficient IgA1,” “ o ‐glycosylation” and “gut microbiota” are the hot words that also hint the research hotspots in the pathogenesis of IgAN, which is consistent with the “four‐fit” process of the IgAN pathogenesis. The mucosal immune system is reported to be a key factor in triggering IgAN, and the “gut‐kidney axis” is proposed to be involved in its development 19 . Gut microbiota dysbiosis was reported in the pathogenesis of IgAN, in which Paraprevotella and Streptococcus showed a higher proportion in patients with IgAN, 20 and the disturbance of intestinal microflora may be associated with the severity of IgAN 21 .…”

“…The mucosal immune system is reported to be a key factor in triggering IgAN, and the “gut‐kidney axis” is proposed to be involved in its development. 19 Gut microbiota dysbiosis was reported in the pathogenesis of IgAN, in which Paraprevotella and Streptococcus showed a higher proportion in patients with IgAN, 20 and the disturbance of intestinal microflora may be associated with the severity of IgAN. 21 Ai et al 22 have reported recently that there is a specific emphasis on the present state of intercommunication between gut microbiota and kidney diseases.…”

Hirudin in the Treatment of Chronic Kidney Disease

“…IgA Nephropathy (IgAN) is the most common primary glomerular disease in the world and a significant cause of ESRD, which is characterized by massive mesangial deposition of IgA-immune complexes and mesangial expansion [ 124 ]. Imbalanced T cell function and secretion of pro-inflammatory factors are involved in the development of IgAN [ 125 ].…”

A PRoliferation-Inducing Ligand (APRIL) in the Pathogenesis of Immunoglobulin A Nephropathy: A Review of the Evidence

“…Immune complexes consisting of Gd-IgA1 and autoantibodies then form and circulate (hit 3) and are deposited within the glomerular mesangium (hit 4) [56,57]. Subsequently, cytokine production at the sites of the immune complex deposition result in localized inflammation and activation of the complement system, renin angiotensin system, and stimulation of mesangial proliferation [58]. IgA antibodies provide the first line of defense against infection at mucosal surfaces, neutralizing bacterial and viral pathogens and maintaining mucosal homeostasis [59].…”