Understanding complete remission, partial remission and relapse of proteinuria in FSGS

You may not think about your kidneys often, but they are the bookkeepers of your body. They manage, among other duties, the delicate balance of the blood's composition. The glomeruli — the dense network of blood vessels in the kidneys — are key in this process. The glomeruli act as a filter, separating and removing waste from the blood.

But the glomeruli can become damaged. Focal segmental glomerulosclerosis (FSGS) is a specific kind of kidney damage that occurs when scar tissue develops in the glomeruli. FSGS isn't a kidney condition but rather a "pattern of injury" that can be seen under a microscope, says nephrologist and FSGS researcher Fernando C. Fervenza, M.D., Ph.D., at Mayo Clinic in Rochester, Minnesota.

There are many reasons why FSGS may develop. Circulating antibodies or certain infections can trigger this type of kidney damage. Some people may have a genetic predisposition. Children born with a single kidney, those with a low birth weight or those who have been diagnosed with reflux nephropathy have a higher risk of the condition. The cause of FSGS plays an important role in determining the best treatment approach. But if left untreated, FSGS can permanently damage the kidney's function and, in some situations, may progress to kidney failure.

Proteinuria — excess protein in the urine — is often a sign of FSGS. And it's typically the most important way your care team assesses your long-term prognosis, tracks FSGS progression and determines how effective treatments are over time.

Below, Dr. Fervenza discusses the importance of proteinuria and its role in determining FSGS remission.

The glomeruli act like a filter that catches and sorts waste in the blood. The filter works by letting tiny molecules, such as water, minerals and waste, pass. Larger molecules, such as proteins and red blood cells, are too big to pass through the filter. The waste is then moved out of the body via urine.

With FSGS, scarring injures the glomeruli and can prevent them from filtering the blood as effectively. As a result, protein can slip through the filter and end up in the urine. Proteinuria can make the urine look foamy, but the only way to tell how much protein is present is through a uranalysis test.

Initially, Dr. Fervenza says, proteinuria is not necessarily a sign that irreversible kidney damage has occurred. Rather, it is a sign that the permeability of the glomeruli has been breached, which means early intervention is important.

"It's always a question of time and how fast we can provide treatment," Dr. Fervenza says. "If at all possible, the goal is to completely get rid of proteinuria because that is equal to better long-term kidney outcomes and preserved function." Addressing proteinuria early and effectively is especially important for people with primary FSGS and those who develop nephrotic syndrome. Nephrotic syndrome develops when too much protein is passed in the urine. It can cause symptoms such as severe swelling, fluid retention, fatigue and loss of appetite.

In short, proteinuria provides critical insights into how the glomeruli are functioning and how FSGS may affect your kidneys long term. Nephrotic proteinuria, for example, is associated with an increased risk of kidney failure. Meanwhile, lower levels of proteinuria significantly improve the chance for long-term kidney function and organ survival.

There are a number of possible treatments for FSGS. To get a sense of your options, read Mayo Clinic’s guide to FSGS treatments. Dr. Fervenza stresses that the right approach to treatment depends on the type of FSGS you have.

Generally speaking, the goal of treatment is to prevent disease progression, protect kidney function and experience a remission of proteinuria. Some people will experience full remission of FSGS. But for others, Dr. Fervenza says only partial remission may be possible — particularly those who have already developed structural damage to the kidneys.

Both remission and partial remission of FSGS are determined by the presence of proteins and other markers, such as creatinine, in the urine.

Complete remission is typically defined as:

• Proteinuria has been reduced to less than 0.3 grams per day or the protein-creatinine ratio is less than 300 milligrams per gram (mg/g).
• Serum albumin protein is greater than 3.5 grams per deciliter (g/dL).

Partial remission is typically defined as:

• Proteinuria has been reduced to levels between 0.3 to 3.5 grams per day or protein-creatinine ratio is between 300 to 3,500 (mg/g).
• There has been 50% decrease in proteinuria.

If you experience remission, Dr. Fervenza says your care team will generally keep your medication plan steady for at least another six months. After that, your care team may recommend gradually reducing the medication dose while checking regularly for changes. If your proteinuria comes back or begins to rise, your care team will likely recommend increasing your medication dose and continuing with medications for a longer period of time — likely 1 to 2 years — or switching to a different treatment option. For some people, it may be possible to stop medications altogether.

It's important to understand that FSGS remission isn't always permanent. Dr. Fervenza estimates that approximately half of people with the condition will at some point experience a relapse, which means proteinuria and other symptoms may return. Some people may require ongoing medicines to stay in remission.

Relapse is typically defined as:

• Proteinuria greater than 3.5 grams per day or a protein-creatinine ratio greater than 3,500 (mg/g) after complete remission or a 50% increase in proteinuria after a partial remission.

With FSGS, it's critical to avoid falling into a cycle of remission and relapse. When this happens, Dr. Fervenza says, it's more likely that you will experience permanent damage to the glomeruli and lose kidney function over time.

As always, talk with your care team about your FSGS treatment options, how often you should be tested for proteinuria and the best path toward remission.