What is new in the pathogenesis and treatment of IgA glomerulonephritis

Abstract

Recently, new findings have been clarified concerning both pathogenesis and treatment of IgA nephritis. The four hits theory has been confirmed but several genetic wide association studies have allowed finding several genes connected with the pathogenesis of the disease. All these new genes apply to each of the four hits. Additionally, new discoveries concerning the microbiota and its connection with immune system and IgA generation have allowed finding out the role of the mucosa in IgA nephropathy pathogenesis. The IgA treatment is also changed included the future possibilities. The treatment of the chronic kidney disease, associated with the nephropathy, is mandatory, since the beginning of the disease. The classical immunosuppressive agents have poor effect. The corticosteroids remain an important cornerstone in any phase of the disease. More effect is related to the treatment of B cells and plasma cells. In particular, in very recent studies have been documented the efficacy of anti B cell-activating factor and anti A proliferation-inducing ligand agents. Most of these studies are to date in phase II/III. Finally, new agents targeting complement are arising. These agents also are still in randomized trials and act principally in hit 4 where the immunocomplexes in the mesangium activate the different pathways of the complement cascade.

Keywords: IgA nephropathy; Anti IgA autoantibodies; Genetic wide association studies; Microbiota; Anti B cell-activating factor agents; Anti A proliferation-inducing ligand agents; Anti complement agents

Core Tip: Genetic wide association studies (GWAS) and studies on microbiota allowed finding new aspects in pathogenesis of IgA nephropathy. GWAS allowed finding new genes related to the different IgA nephropathy phases. Microbiota allowed finding new roles exerted by microbes in mucosa immune system and in IgA pathogenesis. Treatment of chronic kidney disease must be always associated to the immune treatment. In the latter fundamental role is exerted by steroids. Recent studies found the relevance of anti B cell-activating factor and anti A proliferation-inducing ligand agents even if the majority of these studies are still in phases II/III. Similarly in premarketing studies are the anti-complement agents.