Focal Segmental Glomerulosclerosis (FSGS)

Focal segmental glomerulosclerosis (FSGS) is a pattern of glomerular injury characterized by sclerosis, or scarring, affecting some glomeruli (focal) and only portions of the affected glomerular tuft (segmental). It is not one single disease with one cause. The same biopsy pattern can result from primary podocyte injury, an inherited podocyte defect, or a secondary response to another stress. Podocytes form part of the glomerular filtration barrier. When they are injured, their interdigitating foot processes flatten and separate, allowing albumin and other plasma proteins to pass into the urine. Primary FSGS is characterized by nephrotic-range proteinuria greater than 3.5 g in 24 hours, serum albumin below 3.0 g/dL (3.0 g/dL), and diffuse foot-process effacement on electron microscopy, with no identified secondary cause. Urinary protein loss lowers plasma oncotic pressure. Fluid then moves into the interstitial space, producing periorbital or dependent edema; the resulting reduction in effective circulating volume can activate the renin–angiotensin–aldosterone system and promote additional sodium and water retention. This is why a patient can have marked edema while still being vulnerable to intravascular depletion. The liver also increases lipoprotein...