Focal Segmental Glomerulosclerosis (FSGS): Understanding Your Pathology Report

By Jason Wasserman MD PhD FRCPC
July 20, 2026

Focal segmental glomerulosclerosis, almost always shortened to FSGS, is a pattern of scarring in the kidney’s tiny filters, called glomeruli. Its name describes exactly what the pathologist sees: hardening or scarring (sclerosis) affecting only part (segmental) of some, but not all, of the glomeruli (focal). It is one of the most common causes of heavy protein loss in the urine, and it is a leading cause of kidney failure from glomerular disease.

An important idea to hold onto from the start is that FSGS is not a single disease but a pattern of injury with several different underlying causes, and those causes are treated very differently. Sorting out which cause applies is the central task after the diagnosis, and much of your pathology report and the testing around it is aimed at that question.

This article will help you understand the findings in your pathology report for FSGS, what each term means, and why it matters for your care.

What do the kidneys do?

The kidneys filter the blood, removing waste and extra water as urine while keeping the body’s salts and fluids in balance. The filtering happens in millions of tiny units called nephrons. At the start of each nephron is a cluster of small blood vessels called a glomerulus (the plural is glomeruli), which works like a sieve. Wrapped around the outside of this sieve are specialized cells called podocytes, whose interlocking “foot processes” form the final barrier that keeps protein in the blood. FSGS is fundamentally a disease of the podocytes: when they are injured, protein leaks into the urine, and where podocytes are lost, the filter scars. This is why podocytes and the glomerulus come up throughout the report.

What causes FSGS?

Because FSGS is a pattern of injury rather than one disease, it has several distinct causes, and identifying which one applies is the most important step after the biopsy, because it determines the treatment. Broadly, there are three groups.

Primary (idiopathic) FSGS — No external cause is found. It is thought to be driven by a factor in the blood that injures the podocytes, and it typically causes sudden, heavy protein loss. This is the form most likely to respond to treatments that suppress the immune system, and the form most likely to return in a transplanted kidney.
Secondary (adaptive) FSGS — The scarring develops because the remaining glomeruli are overworked, a response to another condition rather than a direct attack on the podocytes. Causes include obesity, a reduced number of working nephrons (for example, after loss of a kidney or with aging), high blood pressure, and certain other kidney conditions. This form usually causes more gradual protein loss and does not respond to immune-suppressing treatment; instead, the underlying cause is addressed.
Genetic and other specific causes — Some FSGS is caused by inherited changes in one of many genes that keep podocytes healthy, which is a more common cause in children and in people with a family history. Other specific causes include certain viral infections and some medications. A gene called APOL1 deserves special mention: particular versions of it, found mainly in people of sub-Saharan African ancestry, substantially raise the risk of FSGS and are linked to a more difficult course.

Distinguishing these groups matters enormously, because the treatment that helps one can harm another. Immune-suppressing drugs that benefit primary FSGS offer no benefit in secondary FSGS and expose the person to side effects for nothing, which is why so much attention goes into determining the cause.

What are the symptoms of FSGS?

The symptoms of FSGS come from protein leaking into the urine, and their intensity often reflects whether the disease is primary or secondary. They may include:

Foamy or bubbly urine, from protein in the urine (proteinuria).
Swelling (edema) of the legs, ankles, feet, or around the eyes, from fluid retention.
Weight gain from retained fluid.
High blood pressure.
Fatigue, and in more advanced disease, the effects of reduced kidney function.

When the protein loss is very heavy, it produces a pattern called nephrotic syndrome: heavy proteinuria, low protein levels in the blood, swelling, and often high blood lipids. Primary FSGS tends to cause this full picture suddenly, while secondary FSGS more often causes milder, more gradual protein loss.

How is the diagnosis made?

FSGS is a diagnosis that can only be made from a kidney biopsy, in which a thin needle is used to take one or more small cores of kidney tissue that a pathologist examines under the microscope. Blood and urine tests show the protein loss and measure kidney function, but they cannot show the scarring pattern that defines FSGS. The biopsy is examined in three complementary ways.

Under light microscopy, the pathologist looks for the defining feature: scarring affecting part of some glomeruli. Immunofluorescence, which uses tagged antibodies to detect deposited proteins, is usually negative or shows only limited, nonspecific deposits; its main purpose here is to rule out other glomerular diseases that can look similar. Electron microscopy, which magnifies the tissue enormously, shows the injury to the podocytes directly, in particular a change called foot process effacement, where the delicate interlocking feet of the podocytes flatten out. This podocyte injury is the underlying event in FSGS, and its extent can help suggest whether the disease is primary (usually widespread effacement) or secondary (usually more limited).

Why the biopsy can sometimes miss it

The word “focal” carries a practical consequence worth understanding. Because only some glomeruli are scarred, and only part of each, a small biopsy sample may by chance contain only unaffected glomeruli and miss the scarring entirely. When the clinical picture strongly suggests FSGS but the biopsy does not show it, the diagnosis is not necessarily excluded, and a repeat biopsy or careful correlation with the clinical findings may be needed. If your biopsy result seemed uncertain or a second biopsy was recommended, this sampling issue is often the reason.

The FSGS variants (Columbia classification)

When FSGS is found, pathologists describe which pattern, or variant, it shows, using a system known as the Columbia classification. The variant is based on the appearance and location of the scarring under the microscope, and it can carry information about the likely cause and outlook, so it often appears on the report. There are five variants:

Not otherwise specified (NOS) — The most common variant, and the default when the scarring does not fit one of the specific patterns below. Many other variants also evolve into this pattern over time.
Tip variant — The scarring is located at the point where the filter meets the tubule that carries urine away. This variant tends to respond best to treatment and has the most favorable outlook.
Perihilar variant — The scarring is concentrated near the point where blood vessels enter the glomerulus. It is the pattern most often seen in secondary (adaptive) FSGS, such as that related to obesity or reduced nephron number.
Cellular variant — An uncommon pattern with a filled-in, cell-rich appearance, thought to represent an earlier or more active stage of injury.
Collapsing variant — The filter collapses in on itself, with overlying podocytes multiplying. This variant progresses the fastest and has the least favorable outlook, and it is the pattern most often linked to APOL1 gene variants and to certain viral infections.

The variant is one piece of the picture rather than the whole story. It is interpreted together with the amount of scarring, the podocyte findings on electron microscopy, and, most importantly, the clinical information that separates primary from secondary disease.

Other findings described in the report

Alongside the scarring pattern, the report often describes features that indicate how much damage is present and how advanced it is:

Proportion of glomeruli affected — How many of the glomeruli in the sample show segmental scarring, and how many are entirely scarred (globally sclerosed). A higher proportion reflects more extensive disease.
Global glomerulosclerosis — Glomeruli that are completely scarred and no longer work, reflecting more permanent, long-standing damage.
Interstitial fibrosis and tubular atrophy — Scarring of the supporting tissue and shrinkage of the tubules, usually reported as a percentage. This is one of the strongest predictors of long-term kidney function.
Foot process effacement — The extent of the podocyte injury seen on electron microscopy, described as widespread or limited, which helps distinguish primary from secondary FSGS.

What is the outlook?

The outlook for FSGS varies widely and depends on the cause, the variant, the amount of protein in the urine, and the response to treatment. The single most important factor is how much protein remains in the urine over time: people whose protein loss falls substantially with treatment (a remission) generally keep good kidney function for many years, while persistent heavy protein loss is associated with gradual progression toward kidney failure. Among the variants, the tip variant has the most favorable outlook and the collapsing variant the least. A large amount of permanent scarring on the biopsy, reduced kidney function at diagnosis, and certain APOL1 gene variants also point to a more difficult course.

One feature specific to primary FSGS is worth knowing: it can return in a transplanted kidney, sometimes soon after transplantation, which is why people with primary FSGS are followed especially closely if they go on to need a transplant. Secondary and genetic forms do not recur in this way.

What happens after the diagnosis?

FSGS is managed by a kidney specialist (a nephrologist), and the first and most important step is to determine the cause, because treatment depends entirely on it. The pathology findings, the pattern of protein loss, and sometimes genetic testing guide this. This is a general overview; the specific plan is individual, and this article does not recommend any particular treatment.

Determining the cause — Before treatment, the team works out whether the FSGS is primary, secondary, or genetic, using the biopsy (including the extent of podocyte injury on electron microscopy), the clinical picture, and, in selected people, genetic testing. This step matters because immune-suppressing treatment helps primary FSGS but not the secondary or genetic forms.
Treatment for primary FSGS — Corticosteroids are usually the first treatment, sometimes followed or replaced by other immune-suppressing drugs such as calcineurin inhibitors if steroids are not effective or cannot be used. A newer medication, sparsentan, which reduces protein loss, has been approved for FSGS and adds another option. The aim is to reduce protein in the urine into remission.
Treatment for secondary FSGS — The focus is on the underlying cause, for example weight loss for obesity-related disease, along with drugs that block a hormone system called the renin-angiotensin system (an ACE inhibitor or ARB) to lower protein loss and protect the kidney. Immune-suppressing drugs are generally not used.
Treatment for genetic FSGS — Immune-suppressing treatment is usually not helpful, and care centers on protecting kidney function and managing protein loss. Treatments aimed at specific genetic causes, including drugs targeting APOL1, are an active area of research.
Supportive care and monitoring — For everyone, blood pressure control, reducing protein in the urine, and managing the effects of nephrotic syndrome are central. Kidney function and urine protein are followed over time to judge the response and guide adjustments.

Questions to ask your doctor

Is my FSGS primary, secondary, or genetic, and how was that determined?
Which variant did my biopsy show, and what does that mean for me?
How much of my kidney showed scarring, both segmental and global?
What did the electron microscopy show about the podocytes?
How much protein is in my urine, and what are we aiming for?
What is my current kidney function, and how will it be monitored?
Would immune-suppressing treatment help in my case, or would it not?
Would a newer medication such as sparsentan be appropriate for me?
Should I have genetic testing, including for APOL1?
If I ever needed a transplant, could this come back in the new kidney?
How will we know whether treatment is working?
What signs should prompt me to contact my care team?