The exact mechanism of action of HIV-associated focal segmental glomerulosclerosis (FSGS) remains unknown. However, some researchers suggests that is the result of a direct HIV infection of kidney cells and toxicity of HIV-1 accessory proteins.

HIV-associated FSGS predominantly affects African American men, which suggests that there is a genetic basis for the condition. However, the gene or genes responsible have not yet been identified.

Common symptoms of focal segmental glomerulosclerosis (FSGS) include fatigue, nausea, headache, foamy urine, weight gain, and poor appetite.

The most common clinical feature of FSGS is nephrotic syndrome, which is characterized by generalized edema (fluid in the body tissues, which causes swelling in the ankles, hands, feet, and eyelids), proteinuria (high levels of protein in the urine), hypoalbuminemia (abnormally low levels of albumin, which is normally the most plentiful protein in the blood), and hyperlipidemia (high cholesterol). Edema generally develops over a few weeks, but initial symptoms may appear suddenly in some patients, with weight gain of 15 to 20 or more pounds. High blood pressure is common among most patients. It is especially common among African American men with renal insufficiency because this population is genetically predisposed to develop high blood pressure.

Pleural effusion (fluid in the lung cavity) and ascites (fluid in the abdomen) may occur. Pericardial effusions are rare.

Rarely, patients experience severe renal failure. Symptoms may include altered mental status and advanced uremia (build up of waste in the blood due to severe kidney disease). Symptoms of uremia include nausea, vomiting, bleeding, and seizures.

General: A kidney biopsy is the most definitive diagnostic test for focal segmental glomerulosclerosis (FSGS). In many patients, physical examination findings are normal except for swelling in some or most areas of the body, which is caused by edema (fluid in the tissues).

Kidney biopsy: A kidney biopsy is the standard diagnostic test for FSGS. During the procedure, a needle is inserted into the kidney and a small sample of tissue is removed. The tissue sample is then analyzed under a microscope for scarring, which indicates FSGS.

Urinalysis: A urinalysis, also called a urine sample test, is used to measure the levels of protein in the urine. Elevated levels of protein in the urine (with or without small amounts of blood) may suggest FSGS. However, since many other conditions may cause proteinuria, further testing is necessary for a diagnosis to be made.

In HIV-associated FSGS, renal (kidney) function deteriorates quickly, leading to end-stage renal disease (ESRD) within a few weeks to one year. ESRD typically occurs after the patient experiences chronic kidney failure. ESRD is fatal unless treated with dialysis or kidney transplantation. Common symptoms include unintentional weight loss, nausea or vomiting, general feeing of discomfort, fatigue, decreased urination, generalized itching, easy bruising or bleeding, blood in vomit or stools, muscle twitching or seizures, increased skin pigmentation, nail abnormalities, headache, frequent hiccups, and decreased sensation in the hands, feet, or other areas.