Diagnosed With C3G? Here’s Why You Should Consider Genetic Testing

If you’ve recently been diagnosed with complement 3 glomerulopathy (C3G), you may be wondering what caused it, what the best treatment options are and whether other members of your biological family are at risk.

Genetic testing can help you get the answers you need. Nephrologist Ali Mehdi, MD, explains how C3G genetic testing works and why it might be helpful.

Genetic testing for C3G

Genetic testing can confirm your C3G diagnosis and help you better understand:

• Why you have the rare glomerular disease
• How serious your condition is
• What treatments are most likely to keep your kidneys healthy
• Whether it runs in your family

How fast C3G develops depends on the type you have and whether or not you have a genetic predisposition. So, knowing whether your C3G is acquired or inherited can help your nephrologist determine the best treatments and roughly how long you’ll need them.

“It’s important to know whether or not you have a genetic predisposition because we have new therapeutic options now — and many more in the pipeline,” explains Dr. Mehdi. “If you’re genetically predisposed to C3G, you might require lifelong treatment.”

Because C3G affects everyone differently, it’s important to monitor your symptoms and any changes you experience along the way. There currently isn’t a cure for C3G, but there are two U.S. Food and Drug Administration (FDA)-approved treatments.

How does genetic testing work?

C3G is complicated, but the genetic testing process is pretty straightforward.

To start, your nephrologist refers you to a geneticist. Depending on the available services in your area, the actual test could happen at home or in person. All you have to do is swab the inside of your mouth with a sterile swab or spatula according to the instructions you’re provided. The swab is then sent to a lab for analysis.

When your test results come back, your nephrologist will schedule an appointment to review the results. The geneticist’s report helps them figure out whether you inherited C3G.

“In this case, we’re looking for specific genes that affect your complement system,” explains Dr. Mehdi.

Your complement system is a collection of proteins that are responsible for triggering inflammation, which is an immune response. When it’s working well, your complement system enhances (or complements) your immune system. This makes it better at fighting off bacteria and viruses.

But C3G is, essentially, too much of a good thing.

“If some of the genes that affect your complement system are mutated, it can make your complement system overactive, causing chronic inflammation and kidney damage,” he continues.

About 10% to 20% of people with C3G end up having these specific genetic mutations. If you fall into that category, your provider will use your test results to recommend targeted therapies. They may even recommend that you join a clinical trial.

They’ll also connect you with a genetic counselor. This provider can help determine who else in your family may be at risk of developing C3G. They can also assist you with family planning.

Final thoughts

The term “complement 3 glomerulopathy” only came into being in 2013, although doctors have known for decades about the pattern of kidney damage it causes. These days, research into the condition and clinical trials of targeted therapies are ongoing.

“C3G is rare. And for the longest time, we didn’t have a lot of information or guidance about treating it because of the gravity of the disease,” Dr. Mehdi notes. “As we understand more about these diseases at the molecular and genetic level, we’re seeing promising developments that enable us to better help our patients.”

Researchers are learning more about C3G every day. And getting a genetic test allows you to take advantage of the latest science and get answers that might not otherwise be available.

The result? Better, more personalized treatment.

“Ten years ago, if you came to see me, I could maybe control your blood pressure or perhaps take care of certain risk factors. I might put you on a high dose of prednisone, which was all we had to control the inflammation happening in your kidneys,” recounts Dr. Mehdi.

“Now, we have more advanced targeted therapies that can hopefully help control the disease with minimal side effects.”