Focal segmental glomerulosclerosis (FSGS) is a histologic description of a glomerular lesion that is associated with significant proteinuria and the nephrotic syndrome. This pathologic finding can be the result of systemic disorders (termed "secondary" causes of FSGS) or may represent primary disease.

Primary FSGS is itself a heterogeneous disease, likely with multiple pathogenic mechanisms resulting in a similar histologic pattern of injury. Secondary causes include chronic reflux nephropathy, chronic hypertension, and obesity.

Clinical presentations vary widely, but typically individuals with primary FSGS present with the nephrotic syndrome. Secondary FSGS is typically associated with less severe proteinuria, often without hypoalbuminemia or peripheral edema. Patients may require renal transplantation, which may have a high frequency of failure from recurrence of FSGS. An early trial of the small-molecule drug inaxaplin significantly reduced proteinuria for patients with apolipoprotein L1 (APOL1) risk variants G1 and G2, which commonly occur in people descended from sub-Saharan Africa. Studies are ongoing.