If your nephrologist thinks a kidney problem has led to chronic kidney disease (CKD), they may have mentioned conditions like complement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN). These rare kidney diseases share similarities, as well as key differences.

Your nephrologist is likely working to figure out which one of these you’re living with, or whether another condition is affecting your kidneys, because an accurate diagnosis can help you get the right treatment. Here’s what you need to know about how they compare so you can make informed decisions about your health.

C3G and IC-MPGN Share Some Symptoms

Many of the symptoms of C3G and IC-MPGN are the same. Both can cause:

• Hematuria (blood in the urine) that makes blood look red, pink, or brown
• Proteinuria (protein in the urine) that makes blood look foamy or cloudy
• Your body to make less urine than usual
• Significant fatigue
• Reduced alertness
• Swelling throughout the body, especially in the hands, feet, and around the eyes
• High blood pressure

These symptoms can show up in different combinations, and they may be mild for some people and more severe for others. Even if you’ve never had symptoms before, it’s important to know what’s possible with the kidney condition you or your loved one has been diagnosed with. That way, you can monitor yourself or your family member and talk to a doctor if something changes.

C3G can also cause repeated infections, eye problems from a buildup at the back of your eye, trouble with how your body handles fat, and gout — a type of joint pain caused by uric acid.

If you’re having any of these alongside kidney symptoms, you may be more likely to be diagnosed with C3G than IC-MPGN.

Both C3G and IC-MPGN Affect Your Kidneys’ Filters

The reason that so many of the symptoms of these two conditions overlap is that they both affect the filtration system in your kidneys. These are called the glomeruli, and they’re mini filtration units that remove waste from your blood into your urine, so the waste doesn’t build up in your body.

The two conditions damage the glomeruli in slightly different ways, but both make it harder for your kidneys to filter waste from your blood. That’s why many of the symptoms overlap — they relate specifically to problems with the kidneys’ filtering system and what can happen in the body when that system isn’t working well. Some C3G symptoms, however, happen because C3G can also affect other parts of the body, not just the kidneys.

C3G and IC-MPGN Have Overlapping Complications

In addition to having some overlap in symptoms, C3G and IC-MPGN can both have the same complications. Both can lead to hypertension (high blood pressure), kidney failure, and high cholesterol levels. While these complications may not happen to everyone, they’re common enough that it’s important to watch for them. Your healthcare professional can tell you what to look for so you can catch these complications quickly.

C3G has some additional symptoms that don’t come with IC-MPGN.

C3G can also cause additional complications. As noted earlier, it can also lead to gout and certain eye problems. These can be both symptoms and complications: They can be signs that something is wrong (a symptom), and they can also happen later as a result of the disease (a complication).

C3G and IC-MPGN Have Different Causes

C3G and IC-MPGN are both related to the issues in the immune system, particularly the complement pathway that normally fights against invaders like viruses, bacteria, and more.

However, the way this pathway is overactivated in these two conditions is different.

In C3G, the complement system becomes too active, and C3 breakdown products can build up in the glomeruli and damage them over time. This can lead to waste building up in your blood and affecting different parts of your body. Doctors don’t fully understand what causes these changes in the complement system. They may be linked to genetics or triggered by certain infections.

In IC-MPGN, the immune system harms your kidneys in a different way. To fight germs, your body makes proteins called antibodies (also called immunoglobulins) that attach to invaders (called antigens). When an antibody sticks to an antigen, they form an immune complex, which helps your body clear the invader.

In IC-MPGN, too many immune complexes form and overactivate a part of the immune system called the complement pathway, including a protein called C3. These immune complexes and C3 can build up in the glomeruli and damage them.

It can be hard even for skilled nephrologists to figure out if you should be diagnosed with C3G or IC-MPGN.

Your nephrology team may not be able to figure out what caused IC-MPGN. Other times, it may be caused by a long-term infection, certain types of cancer, or an autoimmune disease.

Treatment Similarities and Differences

Many of the treatments for C3G and IC-MPGN are the same. Overlapping treatments include:

• Blood pressure medications
• Corticosteroids
• Drugs that suppress your immune system (or parts of it)
• Cholesterol medications
• Medications that target the complement system (though some are approved for only one of these conditions, and research is ongoing)

Some doctors may also suggest plasmapheresis (plasma exchange) for people living with C3G or, in some cases, IC-MPGN. During this treatment, your blood is run through a machine that removes certain proteins, such as antibodies, and then returns the blood to your body. Plasma exchange doesn’t work for everyone, and researchers are still learning who is most likely to benefit. But some people choose to try it as part of their care. Your doctor will choose treatments based on what’s likely causing the problem and how your kidneys are doing.

Distinguishing Between C3G and IC-MPGN

It can be hard even for skilled nephrologists to figure out if you should be diagnosed with C3G or IC-MPGN. To confirm the diagnosis, doctors usually need to do a kidney biopsy. During this procedure, they take a small sample of kidney tissue and examine it in a lab under a microscope.

If you’re already having kidney surgery, doctors may be able to take a small tissue sample during that procedure. If you aren’t scheduled for surgery, they can usually take the sample using a needle inserted through your skin and into your kidney. Either way, your care team will take steps to keep you as comfortable as possible. If the biopsy is done with a needle, you may feel pressure, and you might notice a brief snapping or popping sensation when the sample is taken.

Even with a biopsy, determining whether you’re living with C3G or IC-MPGN can be challenging. Sometimes, the changes look very similar. Sometimes, test results can look more like C3G at one point and more like IC-MPGN at another. Much of the research in this area is relatively new and ongoing, so nephrologists may learn better ways to distinguish these conditions as new data becomes available.

Talk to Your Doctor

If you think that you or someone you love may have C3G or IC-MPGN, talk to your doctor right away. They may order some tests and refer you to a nephrology team that can handle your diagnosis, treatment, and care from there.

If you’re already living with either C3G or IC-MPGN, you should follow up with your kidney team regularly. They’ll continue to keep track of your kidney function, any new or changing symptoms, and new treatment options. They can also help you adapt your treatment plan as the situation with your kidneys changes over time.

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