Costimulatory blockade: A novel approach to the treatment of glomerular disease?

Costimulatory pathways (Cluster of differentiation 28, tumor necrosis factor-related, adhesion and T Cell Ig- and mucin-domain molecules) regulating the interactions between receptors on the T cells and their ligands expressed on several cell types, have a key role in controlling many immunological and non immunological processes. Indeed, accumulating evidence indicate that these molecules are involved in the pathogenesis of numerous conditions, such as allograft rejection, atherosclerosis, rheumatoid arthritis, psoriasis and renal diseases, including glomerulonephritis. Primary or secondary (i.e., associated with infections, drugs or systemic diseases, such as systemic lupus erythematosus, diabetes, etc.) glomerulonephritis represent a group of heterogeneous diseases with different pathogenic mechanisms. Since costimulatory molecules, in particular CD80 and CD40, have been found to be expressed on podocytes in the course of different experimental and clinical glomerulonephritis, costimulation has been thought as a new therapeutic target for patients with glomerular diseases. However, although experimental data suggested that the blockade of costimulatory pathways is effective and safe in the prevention and treatment of glomerular diseases, clinical trials reported contrasting results. So, at this moment, there is not a strong evidence for the general use of costimulatory blockade as an alternative treatment strategy in patients with primary or secondary glomerulonephritis. Here, we critically discuss the current data and the main issues regarding the development of this innovative therapeutic approach.