Ruolo della terapia con anticorpi monoclonali nelle nefropatie immuno-mediate: stato delle conoscenze.

Until recently, the only treatment options for patients with immune-mediated glomerular diseases were based on the use of non-specific immunosuppressants that, however, do not always appreciably ameliorate kidney survival compared with placebo or no treatment. Moreover, these treatments are burdened by a degree of toxicity that may offset the benefits of proteinuria reduction. Monoclonal antibodies have recently become available that specifically target cell populations or molecular mechanisms implicated in the pathophysiology of glomerular diseases. Rituximab, a chimeric monoclonal antibody targeting the CD20 antigen on B cells, has been successfully employed in patients with nephrotic syndrome secondary to membranous nephropathy, minimal change disease, or focal segmental glomerulosclerosis. Its ability to reduce auto- and allo-antibody formation has been instrumental to treat also ANCA-associated vasculitis, lupus nephritis, mixed cryoglobulinemia, and acute humoral rejection. Over the last years, many reports have also documented the efficacy of the anti-C5 humanized monoclonal antibody eculizumab to treat atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, and acute humoral rejection. Their efficacy, together with the excellent safety profiles, makes these antibodies a very helpful tool to treat patiens with glomerular diseases. Moreover, thanks to their specific mechanism of action, monoclonal antibodies are helping to understand the pathophysiology of these diseases more in depth. With the progressively growing use of monoclonals, a crucial issue will be their still high costs that may prevent their use for all patients in need.