Focal segmental glomerulosclerosis (FSGS) is a condition affecting the kidneys that requires a carefully planned approach to care, with treatment strategies aimed at slowing disease progression, reducing protein loss in urine, and protecting kidney function for as long as possible.

Managing Kidney Health When Filters Become Scarred

When someone is diagnosed with focal segmental glomerulosclerosis, the primary goals of treatment revolve around protecting the kidneys from further damage and managing the symptoms that arise from impaired filtering function. Each kidney contains roughly one million tiny filtering units called glomeruli, which work like kitchen strainers to separate waste products and excess fluid from the blood while keeping essential nutrients and proteins where they belong. In FSGS, scarring develops in parts of some of these filters, making it harder for the kidneys to do their job properly. This can lead to proteins leaking into the urine, swelling in various parts of the body, and eventually a decline in overall kidney function that may progress to end-stage renal disease, which is kidney failure requiring dialysis or transplant.^[1][3]

Treatment depends heavily on what type of FSGS a person has. There are three main categories: primary FSGS, where no obvious cause can be identified; secondary FSGS, which happens because of another condition such as a viral infection, obesity, or the use of certain medications; and genetic FSGS, which is inherited through altered genes passed from parents to children. Understanding which type is present helps doctors decide whether to focus on immune-suppressing medications, supportive care to control symptoms and blood pressure, or treatment of an underlying condition that triggered the kidney scarring.^[1][4]

Standard treatments approved by medical societies work to control the complications of FSGS and slow down its progression, while researchers continue to investigate new therapies through clinical trials. These studies test innovative approaches that may offer better outcomes with fewer side effects in the future. However, it is important to note that even with treatment, FSGS remains a serious and often progressive condition, and not all patients respond equally to available therapies.^[9][11]

Standard Approaches to Controlling FSGS

The foundation of FSGS treatment can be divided into two main strategies: non-specific supportive care that addresses symptoms and protects the kidneys, and specific treatments that target the disease process itself, especially in primary FSGS where the immune system may be involved.^[8]

Blood Pressure Control and Reducing Protein Loss

One of the most critical aspects of managing FSGS is controlling blood pressure and reducing the amount of protein leaking into the urine, a condition known as proteinuria. Even when blood pressure is normal, doctors often prescribe medications called angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). These medications work by altering pressure within the tiny blood vessels of the kidney, which helps reduce protein loss. They have been shown to decrease proteinuria even in people whose blood pressure is not elevated, making them a cornerstone of FSGS management regardless of the underlying type.^[8][9]

Many people with FSGS develop high blood pressure over time, and controlling it becomes essential to prevent further kidney damage. Achieving blood pressure within the normal range often requires meticulous attention and sometimes the use of multiple medications in combination. The goal is not just to bring the numbers down, but to protect the delicate filtering structures from ongoing injury.^[8]

Managing Fluid Buildup and Swelling

When the kidneys lose large amounts of protein, the body tends to retain salt and water, leading to swelling in the legs, ankles, face, and sometimes the abdomen. This symptom is part of what doctors call nephrotic syndrome, which occurs in more than 70% of people with FSGS.^[3] To address this, treatment includes limiting daily salt intake to about 2 grams of sodium (equivalent to 6 grams of table salt) and using medications called diuretics to help the body eliminate excess fluid through urine.^[8]

The most commonly used diuretics are loop diuretics such as furosemide. In people with severe swelling, these may need to be given intravenously in a hospital setting. Sometimes, a single diuretic is not enough, and doctors add other types such as metolazone or potassium-sparing agents like spironolactone or triamterene to enhance fluid removal and prevent the loss of potassium, an important mineral.^[8]

Nutritional Adjustments

Because high protein intake can worsen proteinuria and potentially harm kidney function, current recommendations suggest eating about 1 to 1.3 grams of high-quality protein per kilogram of body weight each day. This is a carefully calculated amount designed to provide enough protein to maintain muscle and health without overloading the kidneys. Reducing dietary fat may also help manage the high cholesterol levels that often accompany FSGS.^[8]

Cholesterol Management

People with FSGS frequently develop high cholesterol, which increases the risk of heart disease and may contribute to further kidney damage. Medications to lower lipid levels are an important part of treatment, not only to reduce cardiovascular risk but potentially to slow the progression of kidney disease.^[8][9]

Immune-Suppressing Medications for Primary FSGS

When FSGS is classified as primary—meaning no identifiable cause is found—and a person has nephrotic syndrome with significant proteinuria, doctors may prescribe medications that suppress the immune system. The belief is that an abnormal immune response contributes to damage of the filtering cells, called podocytes, in the glomeruli.^[8][9]

Corticosteroids, such as prednisone, are the first-line treatment for primary FSGS. These medications are typically given for a prolonged period—often several months—because studies have shown that longer courses are more likely to achieve remission, meaning a significant reduction or complete disappearance of proteinuria. However, steroids come with a wide range of side effects including weight gain, mood changes, increased blood sugar, bone thinning, and increased susceptibility to infections. Because of these risks, doctors carefully weigh the benefits against the potential harms.^[9][13]

Unfortunately, many people with primary FSGS are either resistant to steroids from the start or become dependent on them, meaning their disease worsens when the medication is tapered or stopped. In these cases, additional immunosuppressive agents may be used. These include calcineurin inhibitors such as cyclosporine and tacrolimus, which work by blocking certain immune system pathways. Other options include mycophenolate mofetil, which interferes with the production of immune cells, and medications like cyclophosphamide or chlorambucil, though these are used less frequently due to their toxicity.^[11][13]

For some patients, newer agents such as rituximab, an antibody that targets a specific type of immune cell called B cells, have been tried, though evidence for their effectiveness in FSGS is still evolving. The goal of all these therapies is to reduce proteinuria and preserve kidney function, but response rates vary, and not everyone achieves remission.^[9][11]

Duration of Treatment

Treatment with corticosteroids for primary FSGS typically lasts for several months, as shorter courses are less likely to result in remission. If a person responds well, the medication is gradually tapered to minimize side effects. Those who require additional immunosuppressive drugs may need to stay on treatment for extended periods, sometimes years, depending on their response and tolerance to the medications.^[13]

Side Effects and Risks

All medications used to treat FSGS carry potential side effects. Steroids can cause weight gain, high blood sugar leading to diabetes, weakened bones (osteoporosis), cataracts, increased blood pressure, and a higher risk of infections. Calcineurin inhibitors may lead to kidney toxicity with long-term use, high blood pressure, tremors, and an increased risk of certain cancers. Mycophenolate mofetil can cause gastrointestinal upset and a drop in blood cell counts. Because of these risks, ongoing monitoring with blood tests and regular medical visits is essential for anyone undergoing treatment for FSGS.^[9][13]

Emerging Treatments Tested in Clinical Trials

While standard therapies form the backbone of FSGS management, researchers are actively investigating new drugs and treatment strategies through clinical trials. These studies aim to find therapies that are more effective, better tolerated, and more precisely targeted to the underlying causes of kidney damage in FSGS.^[11]

Sparsentan: A Dual-Action Medication

One of the most promising investigational drugs for FSGS is sparsentan, which combines the actions of an angiotensin receptor blocker with an additional mechanism that blocks a receptor called endothelin. Endothelin is a molecule that causes blood vessels to constrict and is thought to contribute to kidney scarring and proteinuria. By blocking both pathways, sparsentan aims to provide greater reduction in protein loss and better protection of kidney function than traditional medications.^[11]

Sparsentan has been tested in Phase II and Phase III clinical trials. Phase II trials are designed to assess whether a drug works and to determine the appropriate dose, while Phase III trials compare the new treatment to the current standard of care in larger groups of patients. In the DUET study, which was a Phase III trial, sparsentan showed the ability to significantly reduce proteinuria compared to a standard ARB. The study also included an open-label extension phase, where all participants received sparsentan to evaluate long-term safety and continued effectiveness. Results from these studies have indicated that sparsentan can lead to sustained reductions in proteinuria, which is a key marker of disease activity in FSGS, and may help preserve kidney function over time.^[11]

Participants in sparsentan trials have been enrolled at sites in the United States, Europe, and other regions around the world. Eligibility typically includes having a confirmed diagnosis of primary FSGS, significant proteinuria despite standard treatment, and adequate kidney function at the time of enrollment. Preliminary safety profiles from these studies have been generally positive, though like all medications, sparsentan carries potential side effects that are carefully monitored.^[11]

Other Investigational Approaches

Beyond sparsentan, several other types of therapies are being explored in clinical trials for FSGS. These include medications that target specific immune pathways, molecules that protect podocytes from injury, and agents that reduce inflammation and fibrosis (scarring) in the kidney. Some studies are investigating whether blocking certain circulating factors—proteins in the blood thought to contribute to podocyte damage—can prevent or reverse FSGS. This is particularly relevant for people in whom FSGS recurs after kidney transplantation, as recurrence is believed to be driven by such circulating factors.^[13]

Clinical trials for FSGS are conducted in phases. Phase I trials focus on safety, testing a new drug in a small number of healthy volunteers or patients to understand how it is processed by the body and what side effects might occur. Phase II trials expand to include more patients with the disease to assess efficacy, optimal dosing, and further safety information. Phase III trials involve large groups and compare the new treatment to existing therapies or placebo to determine whether it offers a meaningful benefit. If a drug successfully completes Phase III, it may be submitted for regulatory approval by agencies such as the FDA or EMA.^[11]

Patients interested in participating in clinical trials should discuss options with their nephrologist, who can help determine whether a trial is appropriate based on individual health status, disease stage, and other factors. Trials are conducted at specialized medical centers, often university hospitals or dedicated research sites, and may be available in the United States, Europe, and other parts of the world.^[11]

Gene Therapy and Precision Medicine

For genetic forms of FSGS, where the disease is caused by mutations in specific genes, the future may include gene therapy or precision-based treatments. Some clinical trials are beginning to enroll patients based on their genetic testing results, offering therapies tailored to the specific molecular defect. This approach is still in early stages, but it represents a shift toward personalized medicine where treatment is matched to the underlying cause of disease at a molecular level.^[21]

Importantly, genetic FSGS generally does not respond to immunosuppressive medications like steroids, so identifying a genetic cause early can spare patients from unnecessary treatments and their side effects. Genetic testing is becoming more widely recommended, especially in younger patients, those with a family history of kidney disease, or those with certain ethnic backgrounds where genetic mutations are more common.^[3]

Most Common Treatment Methods

• Blood Pressure and Proteinuria Control
  • ACE inhibitors or ARBs to reduce pressure in kidney blood vessels and decrease protein loss in urine, used even when blood pressure is normal
  • Antihypertensive medications in various combinations to maintain blood pressure within normal range
• Diuretics and Fluid Management
  • Loop diuretics such as furosemide to promote fluid removal and reduce swelling
  • Additional diuretics like metolazone and potassium-sparing agents (spironolactone, triamterene) for resistant cases
  • Sodium restriction (2 grams per day) to control fluid retention
• Nutritional and Lifestyle Modifications
  • Protein intake limited to 1-1.3 grams per kilogram of body weight daily
  • Reduced dietary fat to manage high cholesterol
• Cholesterol-Lowering Medications
  • Statins and other lipid-lowering agents to reduce cardiovascular risk and potentially slow kidney disease progression
• Immunosuppressive Therapy (Primary FSGS)
  • Corticosteroids such as prednisone, typically for several months
  • Calcineurin inhibitors (cyclosporine, tacrolimus) for steroid-resistant or steroid-dependent cases
  • Mycophenolate mofetil as an alternative or additional immune-suppressing agent
  • Cyclophosphamide or chlorambucil used less commonly due to toxicity
  • Rituximab, an anti-B cell antibody, in selected cases
• Treatment of Secondary Causes
  • Antiviral therapy for HIV-associated nephropathy
  • Weight loss and management of obesity
  • Discontinuation or adjustment of nephrotoxic medications
• Investigational Therapies in Clinical Trials
  • Sparsentan, a dual-action drug blocking both angiotensin and endothelin receptors
  • Agents targeting circulating factors believed to damage podocytes
  • Gene therapy and precision medicine approaches for genetic FSGS