What is Complement 3 glomerulopathy (C3G)?
Complement 3 glomerulopathy (C3G) is a rare, autoimmune chronic kidney disease that affects the way your kidneys function. This condition is caused by an abnormal activation of the complement system – a part of the immune system that protects the body against infections. In C3G, the complement system attacks the healthy cells in your kidneys, leading to inflammation, damage to the glomeruli (tiny blood vessels) in the kidneys and impaired kidney function.
C3G is classified into two separate types based on the type of damage and inflammation pattern as seen under the microscope. Both types of C3G are diagnosed and treated in the same way.
The two types of C3G are called:
- Dense Deposit Disease (DDD)
- C3G Glomerulonephritis (C3GN)
What are glomeruli?
Tiny blood vessels in the kidney that filter toxins and excess fluids from the blood and produce urine.
What does glomerulopathy mean?
Glomerulopathy is the word used to describe damage that has been done to the glomeruli.
What is the complement system?
The complement system is a group of nearly 60 proteins (antibodies) that complement (help) your immune system by identifying and removing things that can cause infection. The proteins circulate through the blood and tissues and are activated when needed to fight viruses and bacteria that can cause disease. There are nine major complement proteins (C1 – C9). One of the major proteins is complement component 3 (C3). Individuals affected with C3G may have low levels of C3 protein circulating, putting them at-risk for infections.
What is C3?
C3 is a specific type of protein in your blood that is part of the complement system. C3 proteins help to destroy germs that can make you sick. If the C3 protein is faulty or becomes overactive, it may attack your own immune system and destroy your healthy cells. In an overactive complement system, C3 proteins may break down into smaller fragments. When blood filters through the kidney, C3 fragments can become deposited in the kidney’s filters, causing inflammation in the kidney.
What causes C3G?
Most cases of C3G are sporadic and the cause of the condition is unknown. Rarely, people may inherit a deficiency of the complement proteins. C3G may be acquired by a faulty gene activating the body’s immune system to attack healthy cells for an unknown reason.
Who is at-risk for CG3?
C3G is an ultra-rare disease. The prevalence is estimated at 2-3 per 1,000,000 people. While C3G may be diagnosed at any age, it is often seen in children and young adults.
What are the symptoms of C3G?
Symptoms of C3G may vary depending from person to person but common symptoms include:
- Blood in urine (hematuria)
- Large amount of protein in the urine (proteinuria)
- Swelling in the legs, ankles, feet, and face (edema)
- High blood pressure (hypertension)
- Decreased urine output
- Fatigue
- Shortness of breath
high levels of protein in your urine may lead to “foamy” appearing urine
How do I know if I have C3G glomerulopathy?
C3G is typically diagnosed through a combination of medical history, physical examination, and laboratory tests. A kidney biopsy - where a small sample of kidney tissue is removed for examination - is usually necessary to confirm the diagnosis. Additional tests, such as blood and urine tests, may also be used to help determine the severity of the disease.
If you have symptoms, it is important to see your healthcare provider. The most common features of C3G are: blood in urine, high levels of protein in the urine and swelling in various areas of the body. Your healthcare provider will conduct a thorough physical exam, including understanding your past family and medical history, and perform blood and urine tests. The blood tests may include a C3 Complement blood test.
Should I be tested for C3G?
If you suspect that you may have C3G, it is important to speak with your healthcare provider as soon as possible to receive an accurate diagnosis and begin a personalized treatment plan just for you. There are several tests your healthcare provider may perform to evaluate your symptoms, such as blood and urine, but the definitive way of knowing whether you have C3G is a kidney biopsy. A kidney biopsy will help confirm the diagnosis as well as determine the extent of damage to the kidneys and develop an appropriate treatment plan.
a procedure that involves inserting a thin needle through the skin directly into the kidney, often using ultrasound to guide the procedure, and taking small pieces of the kidney to examine under a microscope
Can C3G hurt my kidneys?
Yes! When you have C3G, the complement system becomes overactive and damages the tiny glomeruli in the kidneys. Damaged glomeruli means the kidneys are not able to perform their many functions to keep your body healthy. If C3G progresses to kidney failure, or end-stage kidney disease, you may need to consider dialysis or kidney transplant.
Are there treatment options for C3G?
Currently, there is no cure for C3G, but treatment can help manage symptoms and slow down the progression of the disease. Treatment for C3G typically involves a combination of medications, lifestyle changes, and regular medical monitoring. Treatment will be under the guidance of your healthcare provider and directed towards managing your symptoms.
Treatment options for C3G may include:
- Immunosuppressive medications: drugs that suppress the immune system to reduce inflammation and protect the kidneys from further damage. Examples of immunosuppressive medications used to treat C3G include corticosteroids, rituximab, and cyclophosphamide.
- Blood pressure medications: medications that help control high blood pressure, a common complication of C3G. Examples of blood pressure medications include angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs).
- Diuretics: medications that help remove excess fluid from the body and reduce swelling. Examples of diuretics include furosemide and spironolactone.
What are complications related to C3?
C3G is a rare and serious disease. Adjusting to life with C3G can be challenging, but it is important to stay positive and take control of your health. With the right medical care and lifestyle changes, it is possible to live a healthy and fulfilling life with this condition. Under the guidance of your healthcare provider, there are steps you can take to help manage your condition and improve your quality of life.
Some tips for adjusting to life with C3G may include:
- Take your medications regularly
- Follow a healthy diet low in sodium (salt), potassium, and phosphorus
- Stay hydrated by drinking plenty of water
- Exercise regularly
- Avoid smoking and excessive alcohol consumption
- Be certain to monitor your blood pressure and understand your kidney function
- Stay informed about your condition and ask questions during medical appointments
- Connect with a support group or counselor for emotional support
Are there any clinical trials for C3G under investigation?
Yes! There are some therapies under investigation for persons with C3G. More information about clinical trials may be found here.
Additional Resources
- Genetic Testing in Nephrology to Support Early Identification & Interventions of Kidney Disease
https://youtu.be/r7y4qIT3oz8?si=Sy9wI1HZhAWrrPYX - Empowering Hope: Shining a Light on Rare Kidney Disease, an AAKP HealthLine Webinar
https://youtu.be/WOwfpZwBGqE?si=a2BcNURf2NJ_X9-2 - Should You Consider Genetic Testing for Your Kidney Disease? An AAKP HealthLine Innovator Webinar
https://youtu.be/twwZRVeFf5g?si=zEuXU8qkVNtO6OiE - Rare Diseases and Understanding the Implications of Genetic Testing
https://youtu.be/-dmviedyPO0?si=7qEN2c3owdk5mlW2
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