10 Symptoms of Complement 3 Glomerulopathy, a Rare Kidney Condition

Complement 3 glomerulopathy (C3G) is a group of rare kidney diseases characterized by a buildup of proteins in the kidneys. This disease affects approximately 1 to 2 people in a million worldwide. Here are 10 symptoms, including swelling and blood in the urine, that could indicate a person has C3G.

C3G is a rare disease that occurs when the complement system (part of the immune system) becomes overactive. This causes the body to produce too much C3 protein, which can damage the glomeruli or the kidneys’ filtering system.

This causes a number of symptoms, including blood in the urine (hematuria). Damaged glomeruli can leak red blood cells, changing the color of urine from yellow to pink, brown, or red.

See your doctor immediately if you notice blood in your urine so they can investigate the cause.

In addition to blood in the urine, people with C3G usually have high levels of protein in their urine (called proteinuria). This is because their kidneys’ filtering system is not working properly and is allowing proteins to pass into the urine.

Urine that contains too much protein usually appears dark and foamy.

The kidneys’ main job is to filter waste and extra fluids from the blood and create urine to excrete them.

When the kidneys are damaged by C3G, they pass a protein called albumin into the urine, so there is not enough of it in the blood. When people have low albumin levels, water seeps into their tissues, causing swelling. This swelling usually occurs around the feet and ankles, although it can appear in many parts of the body.

The swelling may get worse over time as C3G continues to damage the kidneys. The body continues to retain more sodium and water, leading to further swelling.

There are medications available to relieve swelling and prevent fluid overload.

When C3G progresses to an advanced stage, it can lead to decreased urine flow (oliguria). Because their kidneys are damaged, they cannot produce urine as they normally would.

Decreased urine output usually leads to excessive fluid buildup in the body, leading to swelling, high blood pressure, drowsiness, and possible kidney failure.

High blood pressure (hypertension) is a common sign of kidney problems, including C3G.

Damaged kidneys cannot filter and remove excess fluid from the body. This extra fluid increases the pressure or force in the arteries, leading to hypertension.

High blood pressure is a serious condition that increases the risk of heart disease and kidney failure. So if you have C3G, your healthcare team will likely check your blood pressure regularly and may prescribe blood pressure medications such as ACE inhibitors and ARBs.

Fatigue is a commonly reported symptom of C3G. A 2024 study found that among participants with C3G, 77% reported needing to sleep during the day due to fatigue.

With C3G, damaged kidneys cannot effectively remove waste from the bloodstream. The buildup of these wastes can affect the brain and sufferers may notice daytime fatigue and difficulty concentrating.

Tell your healthcare team right away if you experience any changes in your mood or thinking ability.

In people with C3G, the complement system, part of the immune system, is overactive and sends out infection-fighting C3 proteins when it shouldn’t. This means that when the body is confronted with a dangerous virus or bacteria, the immune system does not have enough proteins to fight the infection.

As a result, people with C3G are at increased risk of infection and often experience frequent infections.

Having C3G can affect your vision over time.

Specifically, people with C3G are at increased risk of drusen, a type of eye disease that occurs when proteins and fats from the complement system build up in the back of the eye. These yellow-colored deposits can distort or blur vision, especially as people age.

Although it is rare, C3G can affect the way fats are distributed throughout the body, especially in people with dense depot disease, one of the specific types of C3G.

Uneven fat distribution, known as acquired partial lipodystrophy, occurs when the body cannot use and store fat effectively. Some areas of the body may appear thin where there is a lack of fatty tissue, while other areas of the body appear larger due to fat accumulation.

In the case of C3G in particular, patients typically experience a reduction in fatty tissue in the upper body. Experts believe this could be because the complement system is involved in the growth of fat cells.

People with C3G and chronic kidney disease are at increased risk of developing gout.

Gout is a chronic disease that occurs when there is too much uric acid, a waste product, in the blood. When the kidneys are damaged and unable to filter uric acid from the blood, it builds up and is deposited in the joints.

Uric acid can form crystals, which causes severe pain in the joints. This most often occurs in the big toe.

Researchers are still learning more about the causes of C3G: it is linked to genetic changes or sometimes infections.

There is no cure for C3G, but many symptoms can be managed with blood pressure medications, medications that suppress the immune system, therapies targeting the complement system, and more.

Lifestyle and diet changes can also help manage high blood pressure and maintain better kidney function, including:

• Limit your sodium intake
• Avoid tobacco smoke
• Maintain a healthy weight
• Do 30 minutes of physical activity almost every day
• Prioritize quality sleep for 7 to 8 hours each night
• Practice stress management techniques