Complement 3 Glomerulopathy (C3G)

Complement 3 glomerulopathy is a group of conditions that affect your immune system and prevent your kidneys from filtering blood as well as they should. Most cases of C3G don’t have a clear cause, but gene mutations and autoantibodies may be responsible. There isn’t a cure, but treatment options exist to help slow it down and reduce your symptoms.


What is complement 3 glomerulopathy?

Complement 3 glomerulopathy (C3G) is a group of conditions that affect how well your kidneys work. Your kidneys filter your blood and remove waste and extra water to make urine (pee).

“Complement 3” refers to a protein in your blood that’s important to your immune system. “Glomerulopathy” (pronounced glo-MARE-yoo-LOP-uh-thee”) refers to damage in your glomeruli (pronounced “glo-MARE-yoo-lye”). Glomeruli are groups of tiny blood vessels in your kidneys that help filter your blood and make pee.

Before 2013, healthcare providers used the terms “membranoproliferative glomerulonephritis (MPGN) type I, II or III” or “mesangioproliferative glomerulonephritis.” However, they now use C3G to classify the group of conditions.

What are the types of C3G?

There are two types of C3G. Healthcare providers determine the type according to what kind of damage and inflammation your glomeruli have when providers look at kidney tissue samples under a microscope. The two types are:

  • Dense deposit disease (DDD, formerly MPGN type II). Providers define DDD according to dense deposits that look like ribbons in the structure of the glomerular basement membrane (GBM). DDD primarily affects children and young adults into their early to mid-20s.
  • C3 glomerulonephritis (C3GN, formerly MPGN type I or III). Providers categorize C3GN according to the absence of the dense deposits in the GBM that define DDD. C3GN primarily affects people 30 and older.

Is C3G chronic?

Yes, C3G is a chronic condition. That means the condition slowly gets worse over time.

How common is C3G?

C3G is very rare. Healthcare providers estimate it affects 2 to 3 out of every 1 million people.


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Symptoms and Causes

What are the symptoms of C3G?

Common symptoms of both types of C3G include:

Both types of C3G can also cause kidney failure. Some kidney failure symptoms include:

  • Fatigue.
  • Nausea and vomiting.
  • Confusion or trouble concentrating.
  • Swelling.
  • Peeing more than usual.

C3G may also cause symptoms that don’t affect your kidneys or how they function. These symptoms may include:

  • Vision problems, specifically from the accumulation of protein and calcium deposits (drusen) in your macula.
  • Lipodystrophy.

What causes complement 3 glomerulopathy?

Complement 3 glomerulopathy occurs when your complement system stops working the way it should. Your complement system consists of proteins in your blood that are part of your immune system. It helps enhance (complement) your immune system by fighting foreign invaders like bacteria and viruses.

If you have C3G, your complement system works harder than normal, which damages your complement 3 (C3) proteins. Damaged parts of your C3 proteins trap themselves in your glomeruli, which makes it harder for your glomeruli to filter your blood or create pee. Without treatment to help slow down the damage, C3G will continue to damage your kidneys and affect your kidney function. This can lead to kidney failure.

In most cases of C3G, healthcare providers aren’t sure what exactly causes your complement system to stop working as it should. However, in some cases, mutations in your C3, CFH and other complement system genes cause C3G. And monoclonal gammopathy may also indirectly cause a kidney injury that impairs the alternative pathway (AP) of complement, which could cause C3G. Monoclonal gammopathy is a blood disorder that affects the plasma cells in your bone marrow.

Medical researchers suspect that autoantibodies may also affect your complement system. Autoantibodies are proteins your immune system makes that target normal body tissues by mistake. There isn’t enough research to be sure that autoantibodies definitively cause C3G.

Who does complement 3 glomerulopathy affect?

Complement 3 glomerulopathy can affect anyone. It equally affects men and people assigned male at birth (AMAB) and women and people assigned female at birth (AFAB). The average age of diagnosis is 23. DDD tends to appear at a younger average age than C3GN.


What are the complications of complement 3 glomerulopathy?

Approximately 50% of people with C3G develop kidney failure within 10 years of diagnosis.

Diagnosis and Tests

How is C3G diagnosed?

A healthcare provider may use various tests to evaluate your kidneys’ health and effectiveness. These tests may include:

  • Blood tests. A provider will use a thin needle (about the size of a standard earring post) to withdraw a small amount of blood from a vein in your arm. They’ll look at your blood at a lab to see if your complement proteins look normal or if you have excessive wastes in your blood.
  • Estimated glomerular filtration rate (eGFR). The eGFR is a value that a provider can calculate from the serum creatinine or cystatin C in a blood sample. It estimates how well your kidneys clean your blood.
  • Urinalysis (urine test). You’ll pee into a special cup and provide the sample to a provider. They’ll test your pee at a lab to see if it contains microscopic amounts of protein or blood.
  • Kidney biopsy. A provider will use a needle or small cut (incision) to remove a small piece of your kidney tissue during a kidney biopsy to examine it at a lab. Your sample may show damaged parts of your C3 proteins in your glomeruli, which may indicate C3G. A kidney biopsy can also help determine what type of C3G you have according to the absence or presence of dense deposits.


Management and Treatment

Is C3G curable?

Currently, there isn’t a cure for C3G. However, healthcare providers and medical researchers are studying the disease and conducting trials in the hope of finding a cure.

How is complement 3 glomerulopathy treated?

There are currently no United States Food and Drug Administration (FDA)-approved treatment options specifically for C3G. However, healthcare providers may prescribe a number of treatments or supportive therapies to slow the progression of C3G and manage your symptoms. These may include:

  • Blood pressure medications. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) reduce the pressure inside your glomeruli, which reduces the amount of protein that leaks into your pee.
  • Cholesterol-lowering drugs. Your provider may recommend statin medications to lower your cholesterol and reduce kidney damage.
  • Change in eating patterns (diet). A dietitian who specializes in kidney diseases (renal dietitian) may work with you to create a special diet to help promote growth or maintain a weight that’s healthy for you. Cutting back on sodium (salt), saturated fat and cholesterol helps reduce damage to your kidneys.
  • Corticosteroids. Corticosteroids (steroids) are anti-inflammatory drugs that help stop your immune system from attacking your glomeruli.
  • Eculizumab. Eculizumab is a monoclonal antibody drug that helps treat rare blood diseases. It may help improve your kidney function by reducing the amount of protein in your pee and improving your glomerular filtration rate.
  • Dialysis. Approximately 50% of people who have C3G develop kidney failure. Dialysis performs the work of your kidneys if you have kidney failure. It cleans your blood by removing wastes and excess fluids.
  • Kidney transplant. A kidney transplant helps treat kidney failure. A surgeon removes your failing kidney with a donor’s healthy kidney.

If you have DDD or C3GN and also have monoclonal gammopathy, a provider will recommend further evaluations to check for underlying conditions.


Can complement 3 glomerulopathy be prevented?

You can’t prevent C3G.

Outlook / Prognosis

What is the outlook for complement 3 glomerulopathy?

About half of people who have C3G develop kidney failure within 10 years of diagnosis. There isn’t a cure for kidney failure. However, with proper diagnosis and treatment, you may still live a long life without many drastic changes to your quality of life.

Living With

How do I take care of myself?

If you have C3G, healthcare providers will work with you to develop the best treatment plan, which may include medications, supportive therapies and changes to your lifestyle. Your treatment plan may include:

  • Taking medications as prescribed by your provider.
  • Changing your eating patterns.
  • Avoiding nonsteroidal anti-inflammatory drugs (NSAIDs), which may increase how fast kidney failure develops.
  • Taking care of your mental health. Having a rare condition can be isolating, and knowing that C3G may cause kidney failure can increase your risk of depression. Talk to your provider about your mental health and get the treatments you need. Ask your provider if there are any support groups for people with C3G. Meeting other people who have C3G can help you feel less alone.

When should I see a healthcare provider?

Contact a healthcare provider if you have symptoms of C3G, including any changes to your pee. These may be signs that your kidneys aren’t working as they should.

If you have C3G, make sure your provider refers you to a kidney specialist who diagnoses and treats conditions that affect your kidneys (nephrologist).

What questions should I ask my healthcare provider?

  • How do you know that I have C3G?
  • If I don’t have C3G, what other condition might I have?
  • What type of C3G do I have?
  • What treatment options do you recommend?
  • What changes should I make to my eating patterns?
  • Do you think I’ll have kidney failure?
  • Can you refer me to a nephrologist?

A note from Cleveland Clinic

Complement 3 glomerulopathy affects the tiny filtering units in your kidneys. If you have C3G, you may notice changes in your pee, swelling, joint pain, vision problems and fatigue.

You may feel a wide range of emotions as you accept your diagnosis and adjust to how C3G affects your life. Give yourself time and space to learn about C3G and your treatment options. Learning about your options and what to expect can help you accept your emotions in healthy and productive ways. Providers are available to you to offer information and guidance. Talk to them if you have any questions or need advice or support.

Medically Reviewed

Last reviewed on 06/10/2023.

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