IgA nephropathy: an overview of the disease, its pathophysiology, and involvement of the gut-kidney axis.

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Its incidence and prevalence vary widely, with estimates of annual incidence ranging from 0.06 to 10.5 per 100,000 per year in adults and children. IgAN represents an important cause of progressive kidney disease, leading to kidney failure in a large proportion of patients, and is associated with a wide spectrum of clinical symptoms, which negatively impact quality of life. Although the consequences of IgAN manifest in the kidney, multiple lines of evidence support a major role for the gut in the pathogenesis of IgAN, including genome-wide association studies that identify risk loci for IgAN that encode genes related to mucosal immunity, maintenance of the intestinal epithelial barrier, and inflammatory bowel disease. Further insights into the underlying disease pathogenesis have led to the development of a multihit model comprising 4 sequential "hits": (i) increased levels of galactose-deficient IgA1 in the systemic circulation, (ii) followed by binding of specific autoantibodies directed against galactose-deficient IgA1, which (iii) form pathogenic IgA-containing immune complexes that (iv) deposit within the glomerular mesangium of the kidney, triggering inflammation, damage, and progressive decline in kidney function. The purpose of this article is to provide an overview of IgAN, examining its epidemiology and clinical features, and the mechanisms underlying its pathophysiology.