Focal segmental glomerulosclerosis (FSGS) is a histopathologic finding of scarring (sclerosis) of glomeruli and damage to renal podocytes.

[11] Response to therapy is variable, with a significant portion of patients progressing to end-stage kidney failure.

[5] An American epidemiological study 20 years ago demonstrated that FSGS is estimated to occur in 7 persons per million, with male African-Americans at higher risk.

[14][15] Podocytes are specialized cells lining the Bowman's capsule that contribute to the filtration barrier, preventing molecules larger than 5 nm from being filtered.

[16] FSGS involves damage to the renal podocytes such that larger molecules, most notably proteins, are filtered and lost through the kidney.

[7][20][21] The focal and segmental nature of disease seen on histology help to distinguish FSGS from other types of glomerular sclerosis.

[22] It is presumed that a set of unidentified circulating factors in the blood contribute to podocyte damage in these cases.

[22] Many causes of secondary FSGS contribute to podocyte injury through hyperfiltration, which is a scenario of excess filtration by renal glomeruli.

[31] Diagnosis of FSGS is made by renal biopsy that includes at least fifteen serial cuts with at least eight glomeruli.

[citation needed] Patients with nephrotic-range (>3.5 g/day) proteinuria have over a 50% rate of progression to end-stage kidney disease at 10 years.