Understanding How Common FSGS Is

Focal segmental glomerulosclerosis is considered a rare disease, but it plays an important role in kidney health worldwide. Healthcare providers diagnose FSGS in roughly 7 out of every 1 million people each year, making it uncommon but significant among kidney conditions^[1]. Despite being rare in the general population, FSGS accounts for a substantial portion of nephrotic syndrome cases, which is a collection of symptoms that occur when kidneys leak too much protein into the urine. Specifically, FSGS is responsible for about 40% of nephrotic syndrome cases in adults and approximately 20% in children^[3].

The incidence of FSGS has been rising over the past three decades in both children and adults across the United States^[6]. Data from the US Renal Data System shows that the rate of end-stage kidney disease caused by FSGS increased dramatically, rising by 11 times between 1980 and 2000^[6]. This increase suggests that more people are being affected by this condition over time, though the reasons for this trend are not fully understood.

FSGS does not affect all populations equally. The disease is more commonly diagnosed in men older than 45 years of age^[4]. Race and ethnicity also play a significant role in who develops FSGS. People of African ancestry are at considerably higher risk, and healthcare providers diagnose FSGS most often in people who are Black^[4][6]. This disparity points to possible genetic factors that influence susceptibility to the disease, particularly genetic variants such as APOL1, which are associated with increased risk and treatment resistance in certain populations^[3].

Although FSGS is rare, it remains one of the most common causes of primary kidney disease affecting the glomeruli, the filtering units of the kidney^[3]. It is also one of the leading glomerular causes of end-stage kidney disease, a condition in which the kidneys can no longer filter waste adequately, requiring patients to undergo dialysis or receive a kidney transplant^[6].

What Causes This Kidney Disease

The causes of focal segmental glomerulosclerosis can be grouped into several categories, and understanding which type a person has is crucial for determining the best treatment approach. The three main types of FSGS are primary, secondary, and genetic^[1].

Primary FSGS, also called idiopathic FSGS, occurs when there is no identifiable cause for the disease. Many people diagnosed with FSGS fall into this category because doctors cannot pinpoint why the scarring began. Researchers believe that in primary FSGS, an unknown protein circulating in the blood damages the filtering structures in the kidneys, specifically the podocytes, which are specialized cells that help keep proteins from leaking into the urine^[4][3]. This type tends to be the most aggressive form of FSGS and is often associated with nephrotic syndrome^[6].

Secondary FSGS happens when the scarring is caused by another underlying medical condition or external factor. A wide range of conditions can lead to secondary FSGS, including viral infections such as HIV, certain medications, drug toxicity, diseases like diabetes or sickle cell disease, obesity, and structural changes in the kidney due to conditions like high blood pressure or aging^[1][4][6]. In secondary FSGS, treating or controlling the underlying cause can often slow the progression of kidney damage and may even lead to improved kidney function over time^[1].

Genetic FSGS, also known as familial FSGS, is a rare form caused by inherited genetic changes. It can occur when several members of a family show signs of FSGS, or when neither parent has the disease but each carries a copy of an altered gene that can be passed on to their children^[1][4]. Genetic markers, particularly APOL1 gene variants found more commonly in people of African descent, are associated with a higher risk of developing FSGS, greater resistance to treatment, and faster progression to end-stage kidney disease^[3].

In some cases, the underlying cause of FSGS remains undetermined even after thorough evaluation. This category is sometimes referred to as FSGS of unknown cause^[1][6].

Who Is at Higher Risk

Certain groups of people and specific health conditions place individuals at higher risk of developing focal segmental glomerulosclerosis. Understanding these risk factors can help with early detection and possibly prevent progression of kidney damage.

One major risk factor is having a family history of FSGS. When the disease runs in families, it suggests a genetic component, and family members may carry gene mutations that increase susceptibility^[21]. People of African ancestry face a significantly higher risk due to genetic variants, particularly APOL1 gene mutations, which are more common in this population^[21][6].

Being born with low birth weight or being born prematurely also increases the likelihood of developing FSGS later in life^[21]. These early life factors may affect kidney development and function, making the kidneys more vulnerable to damage over time.

Obesity is another important risk factor for secondary FSGS. Excess body weight can place increased stress on the kidneys’ filtering system, leading to structural changes and scarring^[1][4][21]. Viral infections, particularly HIV, are well-known causes of secondary FSGS, and managing the infection with appropriate treatment can reduce the risk of kidney damage^[1][21].

Certain medical conditions also increase risk. People with diabetes, sickle cell anemia, or chronic high blood pressure may develop secondary FSGS as a complication of their underlying disease^[1][4]. Additionally, some medications and illicit drug use can be toxic to the kidneys and lead to scarring^[1][4].

Recognizing the Symptoms

Focal segmental glomerulosclerosis does not always cause symptoms that people can notice on their own, especially in the early stages. Many individuals first learn they have a kidney problem during a routine medical exam or when being tested for an unrelated condition^[4].

The most common clinical manifestation of FSGS is nephrotic syndrome, which occurs in over 70% of patients with this condition^[3]. Nephrotic syndrome is characterized by a specific group of symptoms that result from the kidneys leaking large amounts of protein into the urine. People with nephrotic syndrome often experience edema, which is swelling caused by fluid buildup in the body. This swelling typically appears in the legs, ankles, feet, and face, especially around the eyes^[4][6]. The swelling can be uncomfortable and may worsen throughout the day.

Another hallmark of nephrotic syndrome is proteinuria, which means abnormally high levels of protein in the urine. When protein leaks into the urine, it can make the urine appear foamy or frothy, similar to how dish soap looks when mixed with water^[4][6]. At the same time, the level of albumin, a key protein that normally circulates in the blood, drops to lower-than-average amounts, a condition known as hypoalbuminemia^[4].

People with FSGS often experience sudden and unexplained weight gain, not from eating more, but because their bodies are retaining extra fluid^[4]. Despite this weight gain, many patients report having little appetite and difficulty eating, which can be frustrating and confusing^[4].

Hypertension, or high blood pressure, is another common feature of FSGS. It can be severe, with some patients experiencing diastolic blood pressure exceeding 120 mm Hg^[3]. High blood pressure in FSGS not only reflects kidney damage but can also contribute to further deterioration of kidney function if not controlled.

Many people with FSGS also have high cholesterol levels, which increases the risk of heart disease^[4][9]. Fatigue is a frequent complaint and can be debilitating, making it difficult for patients to participate in their usual daily activities^[3][14]. Some patients also experience appetite loss and generalized weakness as waste products build up in the blood.

How to Prevent FSGS

Because the exact cause of primary focal segmental glomerulosclerosis is unknown, there are no guaranteed ways to prevent it. However, for secondary FSGS, addressing the underlying risk factors and conditions can help reduce the likelihood of developing the disease or slow its progression.

Maintaining a healthy body weight is one important preventive measure. Obesity is a recognized risk factor for secondary FSGS, and losing excess weight can reduce stress on the kidneys and lower the risk of developing kidney scarring^[1][4]. Adopting a balanced diet that is low in salt and processed foods can also support overall kidney health and help manage blood pressure.

Managing chronic conditions such as diabetes and high blood pressure is crucial. These diseases are major contributors to kidney damage, and keeping blood sugar and blood pressure within target ranges can protect the kidneys from injury that might lead to secondary FSGS^[1]. Regular monitoring and following treatment plans prescribed by healthcare providers are essential steps.

For people with viral infections like HIV, receiving appropriate antiviral treatment can prevent the development of HIV-associated nephropathy, a form of secondary FSGS^[8]. Avoiding the use of illicit drugs and being cautious with medications that can be toxic to the kidneys also helps reduce risk^[1][4].

If you have a family history of kidney disease or are at higher risk due to your ancestry, regular kidney function screening can help catch early signs of kidney problems before symptoms develop. Simple tests such as urine tests to check for protein and blood tests to measure kidney function can provide valuable information^[9].

How the Disease Affects the Kidneys

Understanding what happens inside the kidneys when someone has FSGS helps explain why the disease causes its particular symptoms. Each kidney contains about 1 million tiny filtering units called glomeruli. These glomeruli work like strainers, allowing waste products and excess fluid to pass through while keeping important substances like proteins and blood cells in the bloodstream^[4].

In FSGS, only some of the glomeruli are affected—this is the “focal” part of the disease name. Within each affected glomerulus, only certain sections or segments develop scarring, which is the “segmental” aspect^[4]. The scarring, or sclerosis, is a hardening of the glomerular tissue that makes it less flexible and less able to filter properly.

The disease process begins with injury to specialized cells within the glomeruli called podocytes. Podocytes play a critical role in maintaining the filtering barrier that prevents large molecules like proteins from leaking into the urine^[3][6]. When podocytes are damaged or lost, the barrier becomes permeable, allowing proteins, especially albumin, to escape into the urine. This loss of protein in the urine is what causes proteinuria, one of the key features of FSGS.

As more podocytes become damaged and the scarring progresses, the affected glomeruli lose their ability to filter blood effectively. The body tries to compensate by increasing pressure in the remaining healthy glomeruli, but this extra strain can eventually damage those glomeruli as well, creating a cycle of progressive kidney damage^[6].

When large amounts of protein are lost in the urine, the level of albumin in the blood drops. Albumin is important for maintaining fluid balance in the body. Without enough albumin, fluid leaks out of blood vessels and into surrounding tissues, causing the edema or swelling that patients experience^[4].

The kidneys also play a role in regulating blood pressure, and as FSGS damages kidney tissue, blood pressure often rises. Hypertension can accelerate kidney damage further, creating another harmful cycle^[3].

Over time, if FSGS is not controlled, the scarring can spread to involve more glomeruli and more segments within each glomerulus. As kidney function declines, waste products that should be filtered out begin to accumulate in the blood, causing symptoms like fatigue, nausea, and poor appetite. Eventually, the kidneys may fail completely, a condition called end-stage kidney disease, which requires dialysis or kidney transplantation to sustain life^[1][3].