If you’ve recently been diagnosed with complement 3 glomerulopathy (C3G), you may anxiously await your treatment plan. Doctors usually recommend a combination of lifestyle changes and medications to treat these kidney diseases (also called renal diseases). These treatment options are designed to protect kidney function, improve overall kidney health, and regulate the immune system to minimize further damage to the kidneys.

This article covers the seven treatments doctors use for C3G and how these therapies work. It also discusses clinical trials as an option for treating 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. C3G is a rare kidney condition caused by overactivation of the complement system, an important part of the immune system that helps protect the body by destroying bacteria and viruses. In people with C3G, this system produces excessive amounts of complement protein C3, leading to the activation of other complement proteins.

These complement proteins form clumps, or immune complexes, that accumulate in the glomeruli. This buildup damages the glomeruli, reducing their ability to function effectively. Over time, this damage can result in chronic kidney disease or even kidney failure if left untreated.

Monoclonal Gammopathy and C3G

Some people with C3G have monoclonal gammopathy. In this condition, the immune system makes 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 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.

For most people with mild C3 glomerulonephritis or dense deposit disease, lifestyle changes will be enough to treat their condition.

Hypertension (high blood pressure) negatively affects many aspects of health. In the kidneys, the extra pressure on 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 fluid throughout the day

ACE inhibitors and ARBs also help treat proteinuria (extra protein in 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 like cholesterol in your blood 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 oral (taken by mouth) corticosteroid that treats inflammatory diseases.

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

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

• Azathioprine (Azasan, Imuran)
• Cyclophosphamide (Cytoxan)
• Mycophenolate mofetil (MMF) (CellCept, Myfortic)
• Sirolimus (Rapamune)
• Tacrolimus (Astagraf XL, Envarsus XR, Prograf)

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

Doctors typically prescribe mycophenolate mofetil with 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 mycophenolate mofetil 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 and then every two weeks. Most people finish treatment after one year.

Similar to eculizumab, ravulizumab (Ultomiris) is a monoclonal antibody that also targets C5. However, ravulizumab has a longer half-life, so you can get infusions less often — every eight weeks instead of every two weeks.

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

5. Plasma Infusion

If you have moderate to severe C3G and taking mycophenolate mofetil plus 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 from the blood. A machine then pumps the filtered blood back into the person’s vein. The National Kidney Foundation notes that plasma infusion and plasma exchange are difficult treatments and 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 called complement inhibitors, which block specific parts of the complement system, have been increasingly studied 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 (Fabhalta) — Blocks complement factor B to stop the complement system from attacking the kidneys
• Pegcetacoplan (Empaveli) — Blocks the activation of C3 proteins to dampen (reduce or decrease) complement system activity
• Avacopan (CCX168) — An oral drug that blocks the activation of C5 proteins to decrease complement system activity, reducing proteinuria
• BCX9930 — A complement factor D inhibitor that targets alternative pathways to slow complement system activity

The results of a 2024 phase 3 clinical trial (late-stage research) found that participants receiving both oral iptacopan and supportive care experienced lasting benefits over 12 months. These included a significant reduction in proteinuria, seen as early as 14 days after starting treatment, and an improved glomerular filtration rate (eGFR), a measure of how well the kidneys filter waste from the blood.

Similarly, a phase 3 clinical trial for pegcetacoplan showed a stabilized eGFR and at least a 50 percent reduction in proteinuria in both adolescents and adults.

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 and replaces it with a healthy one from a donor.

Kidney transplants may not work for everyone with C3G. Recurrence (return of disease) happens in 55 percent to 86 percent of people with C3G after kidney transplantation, typically soon after the transplant. Recurrence can harm the transplanted kidney and is the second most common cause of graft loss, following rejection.

C3G can also damage the newly transplanted kidney because the body continues to make complement proteins that attack healthy kidney tissue. It’s important to stick with your C3G treatment plan to prevent further damage.

Talk With Others Who Understand

At MyKidneyDiseaseTeam, the site for people with kidney disease and their loved ones, members 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 living with C3 glomerulopathy? What treatments has your doctor prescribed? How well have they worked for you? Share your experience in the comments below, or start a conversation on your Activities page.