Complement 3 Glomerulopathy (C3G) is a rare but serious kidney disorder caused by abnormal activity in the body’s immune system. Learn more about C3G’s causes, symptoms, and current treatment options.*

What Causes C3G? The Role of the Complement System

C3G results from dysfunction in the complement system—a network of proteins that normally protects the body by fighting against infections. In C3G, due to either genetic mutations or acquired abnormalities, the system loses its natural checks and balances. This leads to:

• Uncontrolled breakdown of the C3 protein,
• Build-up of protein fragments that get stuck in the kidneys, and
• Damage to the kidneys’ tiny blood-filtering units called glomeruli.
  

C3G includes two main forms: 

• Dense Deposit Disease (DDD), and 
• C3 Glomerulonephritis (C3GN). 

Both types involve damage and inflammation in the glomeruli and gradual loss of kidney function, but they have different tissue patterns when viewed under a microscope.

Symptoms, Diagnosis, and Treatment 

C3G can look different from person to person, especially in the early stages. Some people have no symptoms at first and only find out they have the disease through routine lab tests. 

Symptoms

Over time, the following signs may appear:

• Blood in urine (hematuria). This may be visible (turning the urine pink or dark) or only seen under a microscope.
• Protein in urine (proteinuria).  Too much protein in your urine is a sign that your kidneys aren’t filtering properly. It can also cause your urine to appear foamy.
• Swelling (edema). When your kidneys can’t remove enough fluid, swelling can happen in your feet, ankles, hands, or around your eyes.
• Fatigue. Tiredness is common when waste builds up in your blood.
• High blood pressure. Damaged kidneys can raise your blood pressure, which adds to kidney stress.

Testing: How Doctors Diagnose C3G

Diagnosing C3G takes several steps, because its symptoms are similar to those of other kidney diseases:

• Blood and urine tests look for proteins like creatinine and other waste products.
• Glomerular filtration rate (GFR) is calculated from your blood tests to estimate what percentage of your kidneys are properly filtering wastes and excess fluids.
• Kidney biopsy is the most important test, as it will show where and how C3 is being deposited.

Treatment: What Can Be Done

There is no FDA-approved cure for C3G yet, but treatments focus on protecting your kidneys and slowing the disease.

• Corticosteroids and immunosuppressants. These medicines calm the immune system to stop further damage.
  
• ACE inhibitors and ARBs. These drugs control blood pressure and reduce protein leakage in urine.
  
• Diet changes. A kidney-friendly diet may include less sodium (salt), less protein, and more fruits and vegetables to reduce kidney strain. Consult a renal dietitian.
  
• Complement inhibitors. These are new drugs being studied in clinical trials. They aim to block the overactive complement system directly.
  

Since C3G can progress slowly or quickly depending on the person, it’s important to work closely with a kidney specialist (nephrologist). If the disease worsens, you might need dialysis or a kidney transplant, but with early care, some people live well for many years with careful monitoring and treatment.

*National Kidney Foundation. (n.d.). Complement 3 Glomerulopathy (C3G). https://www.kidney.org/kidney-topics/complement-3-glomerulopathy-c3g 

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