Miriam Chung, MD, is an associate professor in the Division of Nephrology at Icahn School of Medicine at Mount Sinai in New York, New York. She is also the clinical director of the Glomerular Diseases Program at Mount Sinai.
Complement 3 glomerulopathy (C3G) is an extremely rare kidney disease that affects a specific part of the immune system called the complement system. It strikes 1 or 2 out of every 1 million people in the U.S.
Proteins in the complement system help fight infection and remove injured cells from the body. But in people who have C3G, the complement system becomes overreactive and damages the kidney’s filters. As a result, the kidney can’t do its main jobs: filtering blood and removing waste products from the body.
The kidneys then start spilling protein and blood into the urine. Over time, kidney function gets worse. Many people will progress to kidney failure within 10 years, and kidney failure requires a kidney transplant or dialysis to stay alive.
WebMD sat down with Miriam Chung, MD, the clinical director of Mount Sinai’s Glomerular Diseases Program, to discuss how C3G is diagnosed and treated and what people can do to protect their kidneys.
Are there any symptoms of C3G when it’s in its early stages?
If it’s early in the disease process, you may not have any physical symptoms, but as the disease progresses, you may have protein or blood in your urine, foamy or bubbling urine, or swelling in your legs. You may also develop high blood pressure, fatigue, or anemia (low levels of healthy red blood cells).
If there are no symptoms, how can you catch this disease early?
C3G is often caught when you undergo testing for other reasons. Your doctor may see blood in your urine, and that will prompt a full work-up with a focus on your kidneys. Your doctor will test your kidney function and run other blood tests to get an idea of what may be happening. Other tests may include a biopsy of your kidney to look for breakdown products of C3 in the glomeruli (the filtering units of your kidney). We also run a specialized lab test for complement proteins and do genetic testing.
Are there ways to protect the kidneys and stave off kidney failure?
Having high levels of protein in your urine can cause kidney filter scarring over the long term. We will take steps to help protect your kidneys. This can include prescribing blood pressure-lowering medications that protect kidneys by lowering protein in urine. These include angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Other medications, such as sodium-glucose cotransporter (SGLT) inhibitors, can protect the kidneys' filters. These are considered supportive measures only. They are not specific for people with C3G.
How do you monitor people with C3G to see if the disease is progressing?
We monitor patients every few months to stay on top of their care. Tests include estimated glomerular filtration rate (eGFR). That’s a blood test that shows how well your kidneys are working by measuring the waste and toxins in your blood. Another test —
albumin-to-creatinine ratio or uACR — is a urine test that measures how much protein (albumin) and waste product from muscles (creatinine) are in your urine. A higher uACR means there is more damage to your kidneys.
How do you know when it’s time to do more?
If your kidney function starts to decline or the amount of protein in your urine is increasing, specific treatments for C3G are available. There are two types of C3G: dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). Both are treated the same way. Two complement inhibitor drugs were approved for C3G in 2025. Iptacopan helps regulate C3 breakdown and pegcetacoplan blocks C3 to reduce kidney damage. Iptacopan is an oral medication and was shown to lower protein in urine by 35% compared to a placebo or dummy pills. Pegcetacoplan, which is injected or infused twice a week, reduced protein by 68% compared to a placebo in a study. It’s approved for people aged 12 and up. Prior to the approval of these two drugs, we were using broad-acting immunosuppressant drugs, such as corticosteroids and mycophenolate mofetil, to treat people with C3G. These drugs did not have direct effects on the complement system.
Are there any risks associated with these new complement blockers?
These drugs lower your immune system’s ability to fight off infections. You need to get a vaccination for meningitis and Streptococcus pneumoniae (pneumococcus) before starting. We may also prescribe antibiotics to people receiving complement inhibitors to help prevent meningococcal disease. Some patients don’t want to get the vaccines and can’t take these drugs. Others may be worried about the immune suppression and opt not to take them. The cost can be prohibitive if patients’ insurance doesn’t cover the medications.
Are there any lifestyle changes that you recommend for your C3G patients?
Complement inhibitors and the underlying condition lower your immune system’s function, so you have to be careful about avoiding infection. Practice good hand-washing hygiene and wear masks when appropriate. It’s also important to keep your blood pressure in the normal range. This can be done by following a heart-healthy, low-salt diet. The recommended diet for patients with C3G is similar to patients with other chronic kidney diseases. We recommend food rich in vegetables, grains, whole foods, and more plant-based food. Your doctor may also recommend limiting potassium, phosphorus, and protein in your diet to reduce strain on the kidneys. Exercise and weight management are also important for all chronic disease patients, including those with C3G. Some patients may benefit from a cholesterol-lowering medication to help protect their heart.
Is pregnancy risky for women with C3G?
If you are planning to get pregnant and have C3G, you will need to discuss this with your nephrologist beforehand. Some of your medications will need to be changed. ACE inhibitors and ARBs cannot be taken during pregnancy, so you’ll need to come off those medications before becoming pregnant. Also, newly approved C3G treatments have not been studied in pregnant women.
Are there clinical trials looking for other treatments?
Yes, there are ongoing clinical trials looking at new treatments for C3G. You can find information on these trials at clinicaltrials.gov or NephCure. C3G is a rare disease that falls under the umbrella of glomerular disease. If you’ve been diagnosed with C3G, find a specialist in glomerular disease to lead your care team. You can locate a doctor near you through NephCure’s Find a Specialist service.
Is there anything in the C3G pipeline you are excited about?
ADX-038 is a small interfering RNA (siRNA) therapy that also targets a part of the complement pathway, specifically complement factor B, and is being studied in C3G. This drug may require one injection. Studies are ongoing.