Understanding Complement 3 Glomerulopathy (C3G)

Complement 3 glomerulopathy – called C3G – is a rare, chronic kidney disease. It harms the tiny filters in your kidneys. These filters, called glomeruli, clean your blood. They take out waste and extra water to make urine. When C3G damages these filters, your kidneys cannot work as well as they should.^1-3

What causes C3G?

C3G happens because of a problem with a part of your body called the complement system. The complement system is part of your immune system. It is a group of proteins that help fight off germs and infections.¹

In people with C3G, the complement system does not work the right way. It becomes too active or does not turn off when it should. This causes a protein called complement 3 (C3) to build up in the kidney filters. This buildup of C3 damages the filters and makes the kidneys sick.^1-3

Sometimes, the problem with the complement system is caused by changes in certain genes. These gene changes can be passed down through family members, but often they are new in the person with C3G.^1-3

Other times, the problem with the complement system is caused by the body making abnormal proteins called autoantibodies. These autoantibodies can make the complement system too active. Infections can also sometimes play a role in starting or worsening C3G.^1-3

Who is at risk for C3G?

C3G can happen to anyone at any age. However, it is most often found in children and young adults. It affects both men and women equally. But the condition is extremely rare. It occurs in about 1 in every 1,000,000 people.¹

Because some cases of C3G are linked to gene changes, a person might be at higher risk if someone in their family has C3G or another kidney disease. But many people with C3G do not have a family history of the disease.¹

What are the symptoms of C3G?

The signs of C3G can be different for each person. Some people may not have many symptoms at first. When symptoms do happen, they are often related to the kidneys not working well and in the later stages of disease.^1-3

Common symptoms include:^1-3

• Blood in the urine (hematuria) – Your urine might look pink, red, or brown. Sometimes the blood is too small to see without a microscope.
• Protein in the urine (proteinuria) – This can make your urine look foamy or bubbly.
• Swelling (edema) – You might have swelling in your hands, legs, ankles, or feet. This happens because the kidneys are not removing extra fluid.
• High blood pressure (hypertension) – The kidneys help control blood pressure. When they are not working well, blood pressure can go up.
• Feeling very tired (fatigue) – This can happen when waste builds up in the body because the kidneys are not filtering properly. This waste buildup takes a toll on your energy.
• Peeing less than usual

Some people with C3G may also have problems with their eyes or changes in how fat is distributed in their bodies.²

How is C3G diagnosed?

To find out if someone has C3G, doctors use different tests. These include:^1-3

• Urine tests – These check for blood and protein in the urine.
• Blood tests – These measure how well your kidneys are cleaning your blood and look for problems with the complement system.
• Kidney biopsy – This is a very important test for C3G. A doctor takes a tiny sample (biopsy) of your kidney using a thin needle. The kidney tissue is then analyzed under a microscope. This helps doctors see the C3 protein buildup and understand the damage to the filters.

What are the treatment options?

Right now, there is no cure for C3G. However, there are some treatments that can help manage the disease and slow down the damage to the kidneys.^1-3

Treatment for C3G focuses on slowing down the progression of kidney damage by:^1-3

• Controlling blood pressure – Medicines can help lower blood pressure, which protects the kidneys.
• Reducing protein in the urine – Some medicines can help lessen the amount of protein that leaks into the urine.
• Calming the immune system – Immunosuppressive medicines or corticosteroids that quiet down the immune system may be used to reduce the attack on the kidneys.
• Managing swelling – Medicines called diuretics can help the body get rid of extra fluid.

There is 1 drug approved by the US Food and Drug Administration (FDA) to treat C3G. It is called iptacopan (Fabhalta®). It helps to lower the level of protein in the urine and can slow down kidney damage.²

If the kidneys become too damaged, treatments like dialysis or a kidney transplant may be needed. Dialysis is a treatment that does the work of cleaning your blood when your kidneys cannot. A kidney transplant is when a sick kidney is replaced with a healthy one from a donor.^1-3

Doctors may also suggest changes to what you eat to help your kidneys. This may mean sticking to a diet that is low in:^1-3

• Sodium (salt)
• Protein
• Phosphorus
• Potassium

What is the overall outlook?

The outlook for people with C3G is different for everyone. C3G is a progressive disease, which means it gets worse over time and may eventually lead to kidney failure. Kidney failure means the kidneys have stopped working well enough to keep a person healthy.^1-3

However, it is possible to manage C3G with careful medical care and treatment. People with C3G will need to have regular visits with a nephrologist (kidney doctor) to monitor the disease and make sure treatments are working.^1-3

Living with a chronic disease like C3G is difficult. It is important to take care of your overall health, including your mental health. Talking with your doctor and finding support from others can be helpful as you navigate life with C3G.²