Figure 3.

Genetic and environmental contributions to NS. Evidence suggests that SSNS results from combination of immunological and environmental insults to podocyte in a genetic background that is susceptible to podocyte injury and that there is likely a negative correlation between therapy response in NS patients and the degree of genetic podocyte injury. In a simplified view of Nephrotic Syndrome, there is likely a threshold of podocyte injury at which glomerular filtration barrier integrity is lost (red line). In SRNS, the loss of GFB integrity results primarily from genetic insults to podocyte viability that is too profound to overcome with any beneficial cytoskeletal effects of immunosuppressants. Monogenic cases of SSNS likely have less genetic podocyte injury than SRNS, such that immunosuppressive therapy is largely successful at restoring GFB integrity but the overall podocyte viability is still damaged enough to allow environmental factors to influence remission status. More common and polygenic SSNS have a larger contribution of immunological insults to podocyte, which results in a more robust response to immunomodulatory therapy. Frequent relapsers likely have a higher level of baseline podocyte injury than infrequent relapsers.