The Immune System and Idiopathic Nephrotic Syndrome

Abstract

Idiopathic nephrotic syndrome often responds to immunosuppressive treatment. Nevertheless, this syndrome-and the drugs used to treat it-remain important causes of patient morbidity. Idiopathic nephrotic syndrome is usually caused by minimal change disease or FSGS, diseases that primarily affect the podocytes. In spite of decades of research, the underlying causes of both diseases remain incompletely understood. There is, however, a large body of observational and experimental data linking the immune system with both minimal change disease and FSGS, including associations with systemic infections and hematologic malignancies. Perhaps most compellingly, many different immunomodulatory drugs are effective for treating idiopathic nephrotic syndrome, including biologic agents that have well-defined immune targets. In fact, the unexpected efficacy of targeted therapeutic agents has provided important new insights into the pathogenesis of these diseases. Given the large number of drugs that are available to deplete or block specific cells and molecules within the immune system, a better understanding of the immunologic causes of idiopathic nephrotic syndrome may lead to better diagnostic and therapeutic approaches.

Keywords: focal segmental glomerulosclerosis; idiopathic nephrotic syndrome; immunology.

Figure 1.

Multiple functions of B cells in the immune response. Autoimmune B cells may be the primary cause of nephrotic syndrome in some patients through the production of antibodies that target podocyte antigens, such as annexin A2, nephrin, and UCHL1. Production of natural antibodies reactive in injury epitopes may also be a secondary factor in disease progression. Complement activation within the glomerulus generates C3a, which ligates the C3a receptor on podocytes and causes morphologic changes. B cells also have other immune functions that may contribute to disease. They are antigen-presenting cells and modulate T cell immunity. They also produce cytokines and other soluble factors that can affect podocytes. c-mip, c-Maf–inducing protein; NF-κβ, nuclear factor-κappa-β; RelA, REL-associated protein; TCR, T-cell receptor; TLR, Toll-like receptor; UCHL1, ubiquitin carboxyl-terminal hydrolase L1.