C3 Glomerulopathy

Rica Pitogo
May 1
4 min read

Updated: May 8

Authors:

Tejwinder Sandhu, Touro University - California, US

Last Updated: April 30, 2025

What is C3 Glomerulopathy?

C3 Glomerulopathy is a disease that affects the kidneys, especially the glomeruli due to abnormalities in a certain portion of the immune system known as the complement pathway. The complement pathway is made up of proteins that help fight infections. There are many proteins in the complement pathway, and one of the proteins in the complement pathway is named C3. In C3 Glomerulopathy, the complement pathway becomes overactivated and leads to deposition of C3 in the kidney with associated inflammation and damage to the kidneys. Uncontrolled activation of the complement pathway C3 can be caused by either an underlying genetic mutation, infection or autoimmune disease.

There are two main types of C3 Glomerulopathy: C3 Glomerulonephritis and Dense Deposit Disease. Both types result from the same underlying problem of complement pathway overactivation with excessive deposits in the kidney which leads to inflammation. However, they have different appearances under the microscope.

Who is at risk for C3G?

C3G can occur at any age. It especially affects young adults in teens or early 20s but can happen at any age The trigger for the C3G is usually certain types of infections or autoimmune diseases because these conditions can activate the complement pathway.

What are the signs and symptoms of C3G?

Signs and symptoms of C3G are non-specific and may include:

- Blood in the urine (hematuria) – May appear as pink, red, or cola-colored urine

- Foamy urine (proteinuria) – Due to protein in the urine

- Swelling (edema) – Found throughout the body, including legs and face

- Weight gain – Due to excess fluid in the body

- High blood pressure (hypertension)

- Blood clots (mainly associated with severe protein loss and very low levels of blood protein)

- Asymptomatic and abnormalities are only found on blood and urine testing

How is C3G diagnosed?

C3G is usually suspected based on the medical history, clinical examination, and blood and urine tests measuring protein levels in urine. Blood tests that measure the amount of complement proteins are crucial for helping diagnose C3G. A kidney biopsy is required for diagnosis of C3G. A kidney biopsy is a procedure where a doctor takes a small sample of kidney tissue using a needle and studies the sample under a microscope. Specialized complement pathway testing can help in understanding the cause of C3G. Medical genetic testing might be required to evaluate for genetic mutations associated with C3G.

How is C3G treated?

C3G treatment guidelines focus on controlling blood pressure, reducing swelling, and decreasing protein loss in urine (proteinuria). Lifestyle changes are key and include limiting salt in your diet, quitting smoking, reducing alcohol intake, and maintaining a healthy weight with regular exercise and physical activity. Keeping your blood pressure in a good range with medications like ACE inhibitors (such as Lisinopril) or ARBs (such as Losartan) is very important, as these also have protective benefits for your kidneys. Your doctor might prescribe a “water pill” like Furosemide (Lasix) to reduce excessive swelling. Another important goal in treatment is to lower the amount of protein leaking into your urine. Medications called SGLT2 inhibitors (such as empagliflozin, dapagliflozin) have been found to help lower protein loss in your urine and protect your kidney function.

As C3G progresses, different treatments may be needed. Some medications, like ACE inhibitors (such as lisinopril) or ARBs (such as losartan), are commonly used at all stages to help protect your kidneys. Treatments such as steroids (like glucocorticoids) and other medications that weaken the immune system (such as cyclophosphamide), are usually saved for when the disease progresses and unresponsive to earlier treatment. These immune suppression treatments are helpful because C3G is caused by problems with the immune system. However, medicines that weaken your immune system can make it easier for you to get infections, so it’s important to be closely monitored by your doctor. Regular checkups and following your treatment plan are key to protecting your kidneys and keeping them working well.

As of date, Iptacopan (brand name Fabhalta) is the first and only FDA-approved treatment for adults with C3G. This medication works by blocking the complement system which means this medication targets the underlying cause of C3G rather than just managing symptoms. Iptacopan leads to significantly reduced proteinuria which is a key marker of kidney damage. Common side effects include headache, nasal congestion, stomach pain, diarrhea and increased risk of serious infections as this medication targets part of your immune system. The approval of this medication marks a crucial advancement for individuals with C3G, as this is the only targeted therapy available that addresses the disease at the source.

Clinical trials for C3G:

New treatments and therapies are being developed for kidney diseases. Ask your doctor if you want to participate in a clinical trial for C3G. More information is available at: www.enrollmypatient.org