Complement 3 glomerulopathy (C3G) is a group of rare kidney conditions that can occur when part of the immune system produces too many infection-fighting proteins. These proteins accumulate in the kidneys and cause damage. The exact cause of C3G is often unknown, but experts have identified three possible causes.
C3G occurs when a person has an overactive complement system—this is a group of proteins that’s part of the immune system, helping fight off viruses and bacteria. However, with C3G, the complement system is kicked into overdrive, and pieces of complement proteins pile up in the kidneys once they’ve been broken down by the body.
These proteins damage the kidneys’ glomeruli, or their filtering systems, which leads to damage and loss of kidney function.
Experts believe that certain changes in a person’s genes (genetic mutations) might cause their complement system to become overactive. In particular, research has drawn links between C3G and mutations in complement system-related genes such as the CFHR5, C3, or CFH genes.
About 25% of people with C3G have mutations in genes that affect the complement system’s function.
However, experts are still learning more about how genetic changes affect C3G. Many people with these mutations don’t have a family history of the disease. Plus, these mutations only raise a person’s risk for C3G, they don’t cause it every time.
Autoantibodies
Antibodies are proteins that target and attack foreign invaders, such as bacteria, viruses, and fungi, that might otherwise cause infection. However, people also have proteins called autoantibodies that destroy cells, tissues, or other substances made by the body itself, which can lead to autoimmune diseases.
Research suggests that some people with C3G have autoantibodies that interact with certain proteins and disrupt the complement system.
Specifically, the autoantibodies C5 nephritic factor (C3Ne5) and/or C3 nephritic factor (C3NeF) may impair the function of the complement system, leading to C3G. About 40-60% of C3G patients have one of these autoantibodies.
Links to Other Autoimmune Conditions
Most cases of C3G are sporadic, meaning they’re not linked to a family history of the disease.
However, many people with C3G have a personal or family history of autoimmune diseases. These conditions occur when the immune system mistakenly targets and attacks healthy cells and tissues in the body.
Certain autoimmune conditions—such as systemic lupus erythematosus (SLE), where the immune system attacks the skin, kidneys, joints, and more—have also been associated with dysfunction of the complement system. In some cases, people who have SLE also go on to develop C3G, or people with C3G also have other autoimmune diseases.
Experts still don’t fully understand what causes C3G, though evidence suggests autoantibodies or other autoimmune issues cause most cases. Genetic mutations are much less common.
In general, you may have a higher chance of developing C3G if you have:
- Genetic mutations in the CFHR5, C3, or CFH genes
- Familial ancestry from the Mediterranean island of Cyprus
- The autoantibodies C3NeF and/or C5Nef
- Family history of autoimmune conditions
C3G is very rare. In the United States, there are about 1-3 cases per million people.
The underlying cause is unknown in many cases of C3G. There are no proven strategies to prevent it, particularly when genetic changes or autoimmune issues are driving the disease.
However, spotting the symptoms of C3G early can help you seek treatment and lower the risk of complications. Possible symptoms include:
- Pink, red, or brown urine (blood in the urine)
- Cloudy or foamy urine (protein in the urine)
- Reduced urine output
- Swelling
- Fatigue
- High blood pressure (hypertension)
- Frequent infections
If you develop any possible signs of C3G, see your healthcare provider right away. While there is no cure for this disease, many of the symptoms are manageable with treatment.
