7 Treatments for C3 Glomerulopathy

Medically reviewed by Kelsey Stalvey, PharmD
Written by Emily Wagner, M.S.
Posted on July 3, 2024

If you’ve recently been diagnosed with complement 3 glomerulopathy (C3G), you may be anxiously waiting for your treatment plan. Doctors usually prescribe a combination of lifestyle changes and medications to treat these kidney diseases (also called renal diseases). These treatment options can help support kidney health and control the immune system to prevent more damage.

This article covers the seven treatments doctors use for C3G and how they work. We’ll also discuss clinical trials as an option for treating your kidney disease. To learn more about your treatment plan or whether you may qualify for a clinical trial, talk to your nephrologist (kidney specialist).

What Is C3 Glomerulopathy?

C3G is a set of rare complement diseases that damage the kidneys’ glomeruli. These tiny blood vessels filter toxins and waste from your blood to make urine. There are two types of C3G — C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). If you were diagnosed with C3G before 2013, you may know C3GN and DDD as mesangioproliferative or membranoproliferative glomerulonephritis (MPGN).

C3G gets its name from the complement protein C3. Your complement system is a complex part of your immune system. It helps destroy invading bacteria and viruses to protect you from infections. In people with C3G, the complement system is overactivated and makes too many C3 proteins.

For most people with mild C3GN or DDD, lifestyle changes will be enough to treat the disease.

These proteins trigger the activation of other complement proteins. Together, they form clumps, or immune complexes, that become stuck in the kidneys. This damages the glomeruli and makes it harder for them to filter toxins and make urine. Eventually, the kidneys become so damaged that they no longer work properly.

Monoclonal Gammopathy and C3G

Some people with C3G have a condition known as monoclonal gammopathy. In this condition, the immune system has made abnormal antibodies or immune system proteins. If you have C3G and monoclonal gammopathy, your doctor may change your treatment plan.

C3G treatments focus on calming the immune system to prevent it from attacking the kidneys. Below are seven ways doctors treat these diseases to improve your symptoms and life expectancy with C3G.

1. Healthy Lifestyle Changes

No matter what type of C3G you have, your doctor will likely recommend making healthy lifestyle changes. The overall goal is to support your kidney health and prevent further damage. For most people with mild C3GN or DDD, lifestyle changes will be enough to treat the disease.

Hypertension (high blood pressure) negatively affects many aspects of your health. In the kidneys, the extra pressure on your blood vessels causes them to narrow. This narrowing limits blood flow to the kidneys and prevents oxygen and nutrients from reaching the organ tissues. Without enough blood flow, your kidneys can no longer work properly.

Doctors treat high blood pressure by:

  • Prescribing blood pressure drugs, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs)
  • Prescribing diuretics, or “water pills,” to get rid of extra fluid in the body, which lowers blood pressure
  • Encouraging people to eat a low-sodium diet and drink less fluids throughout the day

ACE inhibitors and ARBs also help treat proteinuria — or extra protein in your urine. Proteinuria is a sign of kidney damage seen in people with C3G.

If you have high cholesterol levels, your doctor may prescribe medication to bring them down. Extra fat or lipids in your blood like cholesterol can damage the kidneys. Statins are drugs that help lower your cholesterol levels and also protect against heart disease.

2. Corticosteroids

Some people with C3G make autoantibodies. These immune system proteins mistake your body’s healthy tissues for foreign invaders.

Corticosteroids (steroids) are lab-made medications that help control inflammation from an overactive immune system. They work similarly to the hormone cortisol that’s naturally found in our bodies. Prednisone is a commonly prescribed corticosteroid that treats inflammatory diseases.

Doctors prescribe prednisone along with immunosuppressant medications to treat moderate to severe C3G. Your doctor may have you take these medications every other day to see if your kidney function improves.

Doctors sometimes use immunosuppressants to treat C3G because these drugs can stop autoantibodies from attacking the kidneys.

Prednisone can cause many unwanted side effects, including weight gain, high blood sugar levels, and blurry vision. To avoid these side effects, your doctor will start to lower or taper your dose over time.

3. Immunosuppressants

Immunosuppressants work by suppressing or calming the immune system. Doctors sometimes use them to treat C3G because they can stop autoantibodies from attacking your kidneys. Examples of immunosuppressive medications for C3GN and DDD include:

  • Mycophenolate mofetil (MMF)
  • Cyclophosphamide
  • Azathioprine
  • Sirolimus
  • Tacrolimus
  • Everolimus

Doctors typically prescribe MMF alongside prednisone for C3G. Common side effects of MMF include nausea, vomiting, loss of appetite, and sleep problems.

    4. Monoclonal Antibodies

    Another treatment option for C3G is monoclonal antibodies. Doctors typically prescribe these medications to people who don’t respond to MMF and prednisone. Monoclonal antibodies are protein drugs (immunoglobulins) that block a specific part of the immune system.

    Eculizumab (Soliris) is a monoclonal antibody that attaches (binds) to the complement protein C5. This blocks complement activation and prevents kidney damage. Eculizumab is given as an intravenous (IV) infusion into a vein once a week for up to five weeks. After that, you’ll receive infusions every two weeks. Most people finish treatment after one year.

    Rituximab is another monoclonal antibody sometimes used to treat C3G. It works by blocking B cells — specialized immune cells that make autoantibodies. In theory, rituximab should help treat C3G by lowering autoantibody levels. However, studies so far have found mixed results.

    5. Plasma Infusion

    If you have moderate to severe C3G and MMF and prednisone hasn’t worked for you, your doctor may order a plasma infusion. Plasma is the liquid part of blood that contains proteins. A plasma infusion is given to people with factor H defects to replace the missing protein. Factor H defects are genetic conditions in which the body lacks a protein needed to control the immune system properly, which can lead to kidney problems and a higher risk of infections.

    Doctors may also use plasma exchange to filter autoantibodies out of your blood. The filtered blood is pumped back into your vein by a machine. The National Kidney Foundation notes that plasma infusion and plasma exchange are difficult treatments and they may not work for everyone.

    6. Complement Inhibitors

    Doctors and researchers are always looking for new and better ways to treat glomerular diseases like C3G. In recent years, drugs that block specific parts of the complement system, called complement inhibitors, have been increasingly studied by scientists as a possible way to treat a variety of diseases, including those that affect the kidneys.

    Complement inhibitors have been increasingly studied by scientists as a possible way to treat diseases like C3G.

    Clinical trials are large studies that test how safe and effective a new drug is. Researchers need participants to join clinical trials. If you’re interested, talk to your doctor to see if you’re eligible to join a study.

    Complement inhibitors being studied in clinical trials include:

    • Iptacopan — Blocks complement factor B to stop the complement system from attacking the kidneys
    • Pegcetacoplan — Blocks the activation of C3 proteins to dampen (reduce or decrease) complement system activity

    7. Kidney Transplantation

    Some people with C3G have so much kidney damage that they develop end-stage kidney disease (kidney failure). This means their kidneys no longer work well enough to keep them healthy. During a kidney transplant, the doctor removes the damaged kidney. They then replace it with a healthy kidney from a donor.

    Kidney transplants may not work for everyone. There’s also a chance C3G can damage the newly transplanted kidney. This is because your body will still make complement proteins that attack healthy kidney tissues. It’s important to stick with your C3G treatment plan to stop damage later on.

    Talk With Others Who Understand

    At MyKidneyDiseaseCenter, the site for people with kidney disease and their loved ones, people come together to gain a new understanding of different kidney diseases and share their stories with others who understand life with kidney disease.

    Are you currently living with C3 glomerulopathy? What treatments has your doctor prescribed? How well have they worked for you? Share your experience in the comments below.

      Posted on July 3, 2024
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      Kelsey Stalvey, PharmD received her Doctor of Pharmacy from Pacific University School of Pharmacy in Portland, Oregon, and went on to complete a one-year postgraduate residency at Sarasota Memorial Hospital in Sarasota, Florida. Learn more about her here.
      Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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