Novel Therapies for FSGS: Preclinical and Clinical Studies

Focal segmental glomerulosclerosis (FSGS) is a rare but important cause of end-stage kidney disease in children and adults. Current therapy, consisting of corticosteroids and calcineurin inhibitors, fails to achieve a sustained remission in most patients. Therefore, there is a pressing need to develop new treatments for this glomerulopathy. Traditional approaches have focused on agents that modulate the immune system. In this review, we summarize preclinical and clinical data with newer agents that may ameliorate FSGS. We focus on drugs that inhibit immune injury or inflammation, such as abatacept, rituximab, adalimumab, and stem cells. The potential of agents that block the glomerular action of circulating permeability factors such as soluble urokinase receptor is reviewed. Finally, because fibrosis represents the final common pathway of glomerular damage in FSGS, the experience with a wide range of antifibrotic agents is presented. Despite extensive research on the podocyte dysfunction in the pathogenesis of FSGS, there are few agents that directly target podocyte structure or viability. We conclude that FSGS is a heterogeneous disorder and that intensified translational research is vital to improve our understanding of distinct subtypes that have a defined prognosis and predictable response to targeted therapeutic interventions.