New Aspects on Pathogenesis and Treatment of Membranous Glomerulopathy

The membranous nephropathy (MN) is the major cause of nephrotic syndrome in the adult, account for 20% of cases with annual incidence of 1/100.000. In the past 10 years the role of podocytes has been identified; environmental triggers in genetically predisposed patients can activate podocytes to exhibit antigenic epitopes (receptor of phospholipase A2, thrombospondin type 1) that become targets of specific auto antibodies with subsequent complement activation. The discovery of these mechanisms has opened new horizon in the therapy of MN and novel drugs are available with more specific mechanism of action. Rituximab, a monoclonal antibody directed against CD20 expressed on lymphocytes B, has been used in several trials and appears able to induce remission of nephrotic syndrome in 60% of patients (GEMRITUX trial) with similar risk profile. Nowadays it remains to define the most effective therapeutic pattern. In MN, the concept of targeting disease control has permit novel therapies with specific blocking mechanisms (belimumab) and non-specific (ACTH) and new therapeutic options, such as ofatumumab, bortezomib and eculizumab, that have allowed recognizing pathological processes involved in the glomerular diseases.