Emerging drugs for treatment of focal segmental glomerulosclerosis

Glomerulosclerosis represents the final stage of glomerular injury during the course of kidney disease and can result from a primary disturbance in disorders like focal segmental glomerulosclerosis or a secondary response to tubulointerstitial disease. Overall, primary focal glomerulosclerosis (FSGS), the focus of this review, accounts for 10-20% of patients of all ages who progress to end stage kidney disease. There are no FDA approved therapeutic options that effectively prevent or delay the onset of kidney failure.

Current immunosuppressive therapy and conservative management including inhibitors of the renin-angiotensin-aldosterone axis and sodium-glucose cotransporter are reviewed. FSGS is now recognized to represent a heterogeneous entity with multiple underlying disease mechanisms. Therefore, novel approaches targeting the podocyte cytoskeleton, immunological, inflammatory, hemodynamic and metabolic pathways are highlighted.

A number of factors are driving the development of drugs to treat focal segmental glomerulosclerosis in particular and glomerulosclerosis in general including growing awareness of the burden of chronic kidney disease, improved scientific understanding of the mechanism of injury, and the development of noninvasive profiles to identify subgroups of patients with discrete mechanisms of glomerular injury.