How is Complement 3 Glomerulopathy (C3G) Treated?

If you or someone you care for has been diagnosed with complement 3 glomerulopathy, also called C3G, you likely have many questions. C3G is a very rare kidney disease. Your kidneys have tiny filters called glomeruli. These filters clean your blood, taking out waste and extra water to make urine. In C3G, these filters get damaged.^1,2

What causes C3G?

The problem starts with a part of your body’s defense system, called the complement system. This system has many proteins that work together to fight off germs. In people with C3G, this system does not work correctly.^1,2

A specific protein in this system, called C3, starts to build up in the kidney filters (glomeruli). This buildup causes swelling and damage. Over time, this damage makes it hard for the kidneys to clean your blood like they should.^1,2

C3G can happen because of changes in certain genes or sometimes because the body makes autoantibodies that cause a breakdown of C3.^1,2

Goals of treating C3G

As of now, there is no cure for C3G. So, the main goals of treatment are to help protect your kidneys and slow down the progression of disease. Doctors work to:^1-3

• Lower the amount of protein that leaks into your urine. Too much protein in the urine is a sign of kidney damage. Reducing it helps protect the filters.
• Control high blood pressure. High blood pressure can cause more damage to the kidneys.
• Manage other symptoms like swelling (edema).
• Slow down or stop the loss of kidney function. The hope is to keep the kidneys working as long as possible and prevent kidney failure.

Different treatment options for C3G

Doctors use different treatments for C3G. The best treatment can be different for each person, depending on how serious the disease is and other health factors.^1-3

Treatments can include:^1-3

• Medications
• Diet changes
• Plasma exchange or infusion
• Dialysis
• Kidney transplant

Medications that help treat C3G

Several different medicines can help slow down the progression of C3G.

Complement inhibitors

Recently, a new medicine called iptacopan (Fabhalta) was approved by the US Food and Drug Administration (FDA) for adults with C3G. This is the first drug approved specifically for the treatment of C3G.⁴

Fabhalta is a complement inhibitor. It works by blocking a part of the complement system called factor B. This is thought to help stop the process that causes the C3 protein to build up in the kidneys. Studies showed that Fabhalta helped reduce the amount of protein in the urine in adults with C3G.⁴

Like all medicines, Fabhalta can have side effects. Possible side effects can include:^4,5

• Common cold
• Headache
• Stomach pain
• Diarrhea

Fabhalta has a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). It has this warning because it can increase the risk of serious infections caused by encapsulated bacteria. If you are taking Fabhalta, you should complete or update vaccination for encapsulated bacteria at least 2 weeks before your first dose of Fabhalta. Talk to your doctor to see if this medicine is a good option for you.^4,5

These are not all the possible side effects of Fabhalta. Talk to your doctor about what to expect when taking Fabhalta. You also should call your doctor if you have any changes that concern you when taking Fabhalta.⁵

Medicines to lower blood pressure

Drugs that help lower blood pressure can also help reduce the amount of protein in the urine. Blood pressure medicines that may be prescribed for people with C3G include:^1-3

• Angiotensin-converting enzyme (ACE) inhibitors
• Angiotensin II receptor blockers (ARBs)

Medicines to lower cholesterol

High cholesterol can also be a problem for people with C3G. Cholesterol-lowering drugs may be prescribed, to help reduce kidney damage. Examples include:^1-3

Statins

Medicines that calm the immune system

Sometimes, doctors use medicines that lower the activity of the immune system. These are called immunosuppressants. These might help if the complement system is overly active. Examples include:^1-3

• Steroids
• Mycophenolate mofetil (CellCept®)
• Rituximab (Rituxan®)
• Cyclophosphamide (Cytoxan®)

Diet changes

Adjusting your diet can help reduce the work the kidneys have to do. A doctor or a dietitian can help you make the right food choices. Often, this means eating a diet low in:^1-3

• Sodium (salt)
• Phosphorus
• Potassium
• Protein

Plasma exchange or infusion

In some cases, doctors might try removing the liquid part of your blood (plasma) and replacing it. This can help remove some of the harmful proteins and replace them with normal proteins.³

When kidneys stop working: dialysis and kidney transplant

For some people with C3G, sadly, the kidney damage can get worse over time, even with treatment. When the kidneys can no longer clean the blood well enough to keep a person healthy, it is called kidney failure or end-stage renal disease. About 50 percent of people who have C3G will have kidney failure within 10 years of diagnosis. If this happens, you may need dialysis or a kidney transplant.^1-3

Dialysis

Dialysis is a type of treatment that does the work that your kidneys cannot do anymore. It uses a special machine to clean your blood and remove extra fluid and waste from your body. Dialysis is a life-sustaining treatment, but it is not a cure for C3G.^1-3

Kidney transplant

Another option is a kidney transplant. This is an operation where a healthy kidney from a donor is placed into your body to take over the work of your own kidneys. While a transplant can greatly improve quality of life, C3G can sometimes come back in the new kidney. Doctors will watch carefully for this after a transplant.^1-3

Can C3G be prevented?

Right now, there is no way to prevent C3G from happening. The causes are usually problems with the complement system that a person is born with or develops sporadically.^1-3

Overall outlook for C3G

C3G is a serious disease that can get worse over time. For about half of the people with C3G, the kidneys will stop working completely (kidney failure) within 10 years of being diagnosed.^1-3

However, not everyone with C3G will have kidney failure. Treatments can help slow the disease down. The outlook can be different for each person. It can depend on things like how old a person is when they are diagnosed and how well their body responds to treatment.^1-3

The approval of new treatments like Fabhalta brings new hope. Scientists are learning more about C3G, and more research is happening to find even better ways to treat it.⁴

Living with C3G can be hard, but working closely with your doctor and healthcare team is very important. They can help you manage the disease and live as well as possible.