FSGS stands for focal segmental glomerulosclerosis, a kidney disease in which tiny filtering units called glomeruli become scarred. Each word in the name describes what’s happening: “focal” means only some glomeruli are affected, “segmental” means only part of each affected glomerulus is scarred, and “glomerulosclerosis” means scarring (sclerosis) of the glomeruli. Over 70% of people with FSGS develop nephrotic syndrome, a condition where the kidneys leak large amounts of protein into the urine.
How the Kidneys Are Damaged
Your kidneys contain roughly one million glomeruli, each a ball of tiny blood vessels that filters waste from your blood while keeping useful proteins in your bloodstream. The filtering barrier depends heavily on specialized cells called podocytes, which wrap around the blood vessels like fingers gripping a ball. Their delicate, finger-like extensions (called foot processes) interlock to form a precise mesh that controls what passes through.
In FSGS, podocytes are injured. Their foot processes flatten out, losing the fine structure that normally blocks proteins from escaping into urine. As damage progresses, podocytes detach from the vessel wall entirely. Unlike most cells in your body, podocytes have very limited ability to regenerate. Neighboring podocytes can stretch to cover the gap, but this compensation has limits. Once enough podocytes are lost, scar tissue forms in that segment of the glomerulus, permanently reducing its filtering ability. Damage to the blood vessel lining inside the glomerulus can also contribute, creating a cycle where injured podocytes harm the vessels and vice versa.
Three Main Types of FSGS
Primary FSGS
Primary (or “idiopathic”) FSGS is thought to be caused by a circulating substance in the blood, possibly a signaling molecule released from somewhere outside the kidneys, that injures podocytes throughout both kidneys at once. It typically comes on abruptly, sometimes producing massive protein loss of 20 grams per day or more. Severe swelling and very low blood protein levels are hallmarks.
Secondary FSGS
Secondary FSGS develops when something identifiable puts excess strain on the kidneys. The most common scenario is maladaptive FSGS, where either the number of working filtering units is reduced (from being born with one kidney, low birth weight, or prior kidney damage) or normal kidneys are pushed beyond their capacity by conditions like obesity, sickle cell disease, or a very high-protein diet. The remaining glomeruli enlarge to compensate, but the added workload gradually injures podocytes.
Certain viruses can also trigger FSGS, with HIV being the best-established cause. Some medications, including certain antivirals, immunosuppressants, and anabolic steroids, can cause it as well. In these cases, FSGS often improves when the infection resolves or the drug is stopped. Secondary FSGS generally produces less dramatic protein loss than the primary form, and full-blown nephrotic syndrome is uncommon.
Genetic FSGS
Genetic FSGS results from mutations in genes that build critical podocyte proteins, including those forming the filtration mesh, the cell’s internal skeleton, or its signaling machinery. It can be inherited in several patterns or appear as a new mutation. When it starts in childhood, it often causes severe nephrotic syndrome. In adults, the genetic form tends to progress more slowly, with protein loss typically under 5 grams per day. Genetic FSGS is usually resistant to steroid treatment.
Who Is Most Affected
FSGS can occur at any age, but data from pediatric registries show significant racial disparities. Black and Hispanic children accounted for 23% of all pediatric kidney transplants in the late 1980s but 38% of those performed specifically for FSGS, indicating they are disproportionately likely to progress to kidney failure from this disease. The average age of onset in children is around 7 to 8 years. In adults, FSGS is one of the most common causes of nephrotic syndrome, and these disparities persist.
Symptoms and How It’s Detected
The most noticeable symptom is swelling, particularly in the legs, ankles, feet, and around the eyes. This happens because protein leaking into the urine lowers protein levels in the blood, which normally helps hold fluid inside blood vessels. With less protein, fluid seeps into surrounding tissues. Fatigue and loss of appetite are common. High blood pressure frequently accompanies FSGS and can be severe.
Urine tests typically reveal large amounts of protein and certain types of casts (tube-shaped protein structures formed in the kidney). Red blood cells in the urine can occur but are less typical. In early stages, standard blood markers of kidney function like creatinine often look normal, which means the disease can be silently progressing before kidney function visibly declines on routine bloodwork.
A definitive diagnosis requires a kidney biopsy. Under a microscope, pathologists look for the characteristic pattern of scarring in segments of some glomeruli. In very small biopsy samples, early FSGS can look identical to a milder condition called minimal change disease, because the scarred glomeruli may not have been captured in the tissue sample.
Treatment Approach
No medications are currently approved by the FDA specifically for FSGS. Treatment relies on drugs developed for other conditions. For primary FSGS, high-dose steroids are the recommended first-line therapy, continued until protein levels in the urine return to normal or for up to 16 weeks. If protein loss hasn’t improved by 16 weeks, the disease is classified as steroid-resistant.
For people who can’t tolerate steroids or whose disease doesn’t respond to them, immune-suppressing drugs that target specific white blood cell pathways are the next step, typically given for at least six months before being considered ineffective. Adults with contraindications to steroids may start with these alternatives from the beginning.
Secondary FSGS is managed differently. The priority is addressing the underlying cause: weight loss for obesity-related FSGS, stopping the offending medication, or treating the triggering infection.
Long-Term Outlook
Achieving remission, even partial, is the strongest predictor of a good outcome. In a large epidemiological study spanning 20 years, 27.4% of FSGS patients eventually needed dialysis or a kidney transplant, and another 27.4% died during follow-up. Patients who achieved partial or complete remission were significantly less likely to reach kidney failure.
Complete remission means protein in the urine drops below 300 milligrams per day with stable kidney function. Partial remission means a 50% or greater reduction in protein loss, even if it remains elevated. Both outcomes substantially improve the long-term prognosis compared with persistent heavy proteinuria.
Recurrence After Kidney Transplant
One of the more challenging aspects of FSGS, particularly the primary form, is that it can return in a transplanted kidney. This is consistent with the theory that a circulating factor in the blood causes the disease, since a new kidney is exposed to the same bloodstream. In children, recurrence rates for a first transplant range from 20% to as high as 86% depending on the study, with a recent meta-analysis estimating an overall pediatric recurrence rate of about 39%. Recurrence in subsequent transplants approaches nearly 100%.
Risk factors for recurrence include having originally responded to steroids (steroid-sensitive disease) and non-genetic steroid-resistant nephrotic syndrome. Genetic forms of FSGS, by contrast, are less likely to recur in a transplant because the problem was in the original kidney’s cells rather than in the blood. This distinction between primary and genetic FSGS has real consequences for transplant planning and expectations.