6 Types of Treatment for Complement 3 Glomerulopathy

Complement 3 glomerulopathy (C3G) is a rare kidney disease that is also considered an autoimmune disorder. There is no single cure for C3G, but several treatments may slow disease progression, protect kidney function, and reduce symptoms. Treatment is often based on the severity of the disease and its rate of progression.

1. Supportive Kidney Care

Supportive care is the starting point for almost all people with C3G. Supportive care includes treatments that don’t directly address the root cause of the condition, but rather target certain downstream effects. These treatments help protect other parts of the body, such as the heart and blood vessels.

Blood Pressure Drugs (ACE Inhibitors and ARBs)

Medications like angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) help lower blood pressure and reduce protein leaking into the urine. Examples of ACE Inhibitors include:

• Zestril (lisinopril)
• Vasotec (enalapril)
• Lotensin (benazepril)

ARB examples include Cozaar (losartan) and Diovan (valsartan).

A lower level of protein in the urine helps protect the kidneys from further damage. These drugs do not cure the complement problem, but they slow the progression of kidney decline.

Diet and Lifestyle Changes

Your healthcare provider may also recommend:

• Lower salt intake, as high amounts of salt can lead to fluid build-up, swelling, and high blood pressure, which causes further harm to the kidneys and heart
• Managing cholesterol, as high levels can damage kidney blood vessels and impair them further
• Maintaining a healthy weight to control blood pressure and inflammation and prevent other kidney-damaging conditions, such as diabetes

Following these steps can help reduce stress on the kidneys and lower the risk of heart disease.

2. Corticosteroids

Corticosteroids, such as prednisone or dexamethasone, are sometimes used to reduce kidney inflammation and temper the immune system to reduce harm to the kidneys.

Healthcare providers often consider corticosteroids when there is clear evidence of kidney inflammation, as shown by tests such as a biopsy. Treatment is usually started at a low or moderate dose and adjusted based on individual response.

While steroids may help with active inflammation, they do not correct the underlying complement system problem. Long-term use can cause side effects like weight gain, infections, and bone loss.

If kidney function does not improve or side effects become severe, steroids may be reduced or stopped.

3. Other Immunosuppressive Medications

In addition to corticosteroids, other drugs may be used that calm the immune system, known as immunosuppressants. Some examples include:

• Mycophenolate mofetil (MMF), also known as an antimetabolite, limits the activity of immune cells
• Cyclophosphamide, used at lower doses to treat multiple autoimmune diseases, and at higher doses to treat some types of cancer
• Rituximab, a monoclonal antibody also used for many autoimmune diseases and some cancers

These medicines aim to reduce immune-related kidney injury. However, studies show inconsistent results, and many people do not respond well. Because of this, immunosuppressive drugs are no longer considered the best option for many people with C3G.

4. Plasma Exchange Therapy

Plasma exchange is a process where the liquid part of the blood, called plasma, is removed and replaced with donor plasma or a protein solution. Plasma may contain harmful proteins that trigger overactivity of the complement system.

This treatment may be helpful for those with certain autoantibodies that interfere with normal complement control. However, plasma exchange does not fix the underlying cause of C3G, and any benefit is often temporary. Additionally, evidence is limited to small studies and case reports.

Because of this, it is usually used only in selected cases or severe flare-ups. Plasma therapy may be reserved for special situations and is not routine treatment.

5. Complement-Targeted Therapy

As C3G is caused by the overactivation of the complement system, a crucial part of the immune system, newer treatments aim to block this process more directly.

C5 Inhibitors

Eculizumab (brand names Soliris, Bkemv) blocks C5, a protein within the complement system. Some people show reduced protein in the urine and more stable kidney function with the use of eculizumab.

The drug works better in people with strong activation of the final complement pathway, meaning that the C5 protein is a primary driver of their C3G disease. This may be determined using a combination of blood tests, genetic testing, and biopsy findings.

C3 and Alternative Pathway Inhibitors (Newer Therapies)

Newer drugs target the complement system earlier in the pathway, closer to the cause of C3G:

• Fabhalta (iptacopan): Iptacopan was approved by the Food and Drug Administration
  (FDA) in March 2025 to help reduce proteinuria in adults with C3G.
• Zaltenibart and danicopan: Two treatment options still in clinical trial stages, seeking FDA approval. Both of these are being investigated for their benefits in the early stages of the complement system.
• Empaveli (pegcetacoplan): Pegcetacoplan is FDA-approved for use in adults and teens (12 years and older) to reduce protein levels in the urine (proteinuria).
• PiaSkey (crovalimab): Crovalimab is a monoclonal antibody approved for use in a disease called paroxysmal nocturnal hemoglobinuria (PNH), another autoimmune disease associated with complement system overactivation. Due to this shared disease pathway, studies are exploring its potential for treating C3G in addition to PNH.

These therapies represent a major shift toward treating the root cause of C3G rather than just symptoms.

6. Kidney Transplant

Some people with C3G progress to kidney failure and need a transplant.

C3G often comes back in the transplanted kidney, within months to years, because the problem with the complement system remains in the body despite having a new kidney.

Recurrence can damage the new kidney, with early signs including rising protein in the urine or worsening kidney function. Complement-targeted drugs after a kidney transplant may help manage recurrence in some cases.

Because of this risk, transplant patients with C3G require close monitoring and specialized care.

How C3G Treatment Has Changed

Treatment for complement 3 glomerulopathy has changed over time. While older treatments focused mainly on controlling symptoms like inflammation and protein in the urine, or on controlling other effects of the disease such as blood pressure and blood vessel damage, newer therapies target the complement system itself.

Supportive care remains essential, but complement-blocking drugs offer new hope for slowing disease progression. Recently, the use of steroids and immunosuppressants has become less common due to long-term side effects and inconsistent results.

Because C3G is rare and complex, treatment is usually personalized and managed by kidney specialists.