Focal Segmental Glomerulosclerosis (FSGS)

Focal segmental glomerulosclerosis is a pattern of glomerular injury, not a single cause. Focal means that only some glomeruli are affected; segmental means that only part of an affected glomerular tuft is scarred. The injury begins at the podocyte, the specialized cell that forms the final layer of the glomerular filtration barrier. Podocyte foot processes normally help keep albumin and other large proteins in the bloodstream. When podocytes are injured, their foot processes become effaced and the barrier loses selectivity. Protein then spills into the urine. Ongoing injury produces scarring, which reduces functioning filtration surface and can lead to progressive loss of renal function. Primary FSGS is thought to result from a circulating podocyte-toxic factor, a podocyte-specific genetic mutation, or immune-mediated injury. Secondary FSGS develops when another process repeatedly increases glomerular stress or directly injures podocytes. Obesity, hypertension, reduced nephron mass, viral infection, and drug toxicity are examples. That distinction changes treatment. Primary FSGS may respond to immunosuppression. Secondary FSGS generally will not improve with immunosuppression because the continuing problem is hyperfiltration or toxic injury rather than an immune process...