Nephropathy Due to Immunoglobulin A Deposits: Advances in Pathogenesis

IgA nephropathy is considered a distinct form of primary glomerulonephritis. In most cases, the initial clinical presentation is isolated, intermittent or persistent, macro or microscopic hematuria of glomerular origin. However, arterial hypertension and proteinuria may appear in varying degrees. In the 60s it was considered a benign disease with a favorable prognosis, however, prospective studies with long years of follow-up have shown disease progression to complete loss of renal function in pediatric and adult patients. Evidence demonstrates that IgA nephropathy, is an autoimmune disease wherein the kidneys are damaged as innocent bystanders due to deposition of IgA1-IgG immune complexes from the circulation. Patients with IgA nephropathy have elevated circulating levels of IgA1 with some O-glycans deficient in galactose (galactose-deficient IgA1) and these IgA1 glycoforms are recognized as autoantigens by unique IgG autoantibodies. These circulating immune complexes deposit in the glomeruli and activate mesangial cells that respond with mesangial hypercellularity, apoptosis, oxidative stress, complement activation, mesangial matrix expansion, damage to podocytes and proximal tubule epithelial cells, increased glomerular permeability and fibrosis in the glomerular and interstitial compartments. Clinically, these renal lesions will cause hypertension, proteinuria, hematuria, and reduced renal function. The immunopathogenesis of the disease is still not fully understood and further studies are needed. With a better understanding of immunopathogenesis of IgAN it will be possible an earlier diagnosis and more appropriate treatment.