Fig. 1.

Proposed four-hit hypothesis for pathogenesis of immunoglobulin A nephropathy (IgAN). In genetically susceptible individuals, environmental factors are thought to trigger the onset of IgAN. A four-hit hypothesis has been proposed for the disease pathogenesis: increased levels of circulatory galactose-deficient IgA1 (Hit 1) lead to production of autoantibodies (either IgG or IgA, but mostly of the IgG isotype) (Hit 2). This process results in the formation of circulating nephritogenic immune complexes (Hit 3), some of which deposit in the glomeruli and induce kidney injury via mesangial cell activation and proliferation (Hit 4) [32]. There is evidence that the alternative complement pathway and, at least in some patients, the lectin pathway are involved in the pathogenesis of IgAN