glomerulus consists of a set of capillaries from which blood is filtered into Bowman's space. Large molecules, such as proteins, are usually too large to be filtered and instead are retained in the capillaries. FSGS is primarily a disease of the renal glomerulus, the site of filtration of ions and solutes. Podocytes are specialized cells lining the Bowman's capsule that contribute to the filtration barrier, preventing molecules larger than 5 nm from being filtered. FSGS involves damage to the renal podocytes such that larger molecules, most notably proteins, are filtered and lost through the kidney. Thus, many of the signs and symptoms of FSGS are related to protein loss. On histology, FSGS manifests as damage (sclerosis) to segments of glomeruli; moreover, only a portion of glomeruli are affected. The focal and segmental nature of disease seen on histology help to distinguish FSGS from other types of glomerular sclerosis. FSGS can be classified by the putative<unk> of damage to podocytes. Primary FSGS involves<unk>  in which no<unk> is readily identifiable. It is presumed that a set of unidentified circulating factors in the blood contribute to podocyte damage in these<unk> . Secondary FSGS is<unk>  by an identifiable stress or toxin that injures podocytes. Many<unk>  of secondary FSGS contribute to podocyte injury through hyperfiltration, which is a scenario of excess filtration by renal glomeruli. Hyperfiltration can be<unk>  by obesity or loss of the contralateral kidney, among other<unk> . Secondary FSGS can also be<unk>  by toxins, including steroids and heroin. A number of genes have been implicated in FSGS. These include: NPHS1, which encodes the protein nephrin that contributes to the filtration barrier; NPHS2, which encodes the protein podocin found in podocytes; and INF2, which encodes the actin-binding protein formin. The pathogenesis of HIV-associated FSGS is unclear, but may be primarily due to the presence of the G1/G2 risk alleles for APOL1. There is some data to suggest that HIV can infect tubular epithelial cells and podocytes, but much remains to be known.
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