Understanding Proteinuria in C3G

If you’ve been diagnosed with complement 3 glomerulopathy (C3G), you probably know that urine protein-creatinine ratio (uPCR) testing is key to measuring the impact the disease has on your kidneys. But you may be less clear on what exactly the test is measuring.

We asked nephrologist Corey Cavanaugh, DO, about proteinuria in C3G. Dr. Cavanaugh explains why having high levels of protein in your pee is significant and how uPCR testing helps your healthcare provider track your kidney health over time.

C3G and proteinuria

Healthy kidneys filter fluids and waste out of your bloodstream, while leaving behind the substances your body needs.

But if you’ve been diagnosed with C3G, chronic inflammation is damaging your kidneys. It’s sort of like somebody’s poking holes in your filter, which allows protein — something you don’t want to lose — to spill out into your pee. This is known as proteinuria.

Meanwhile, the fluids and waste products that your kidneys are supposed to filter out can build up in your body and make you sick.

“Proteinuria is the best thing we have to predict outcomes of kidney function down the road,” Dr. Cavanaugh says.

uPCR for C3G

uPCR stands for “urine protein creatinine ratio.” It’s a go-to test for measuring proteinuria. In addition to capturing the protein level in your pee, it measures the creatinine content. Creatinine is a waste product that your kidneys are supposed to filter out.

Why use this ratio? Put simply, the protein levels in your pee can vary a lot. So, to help the test be more precise, your protein score is paired with your creatinine score. Seeing these two numbers together helps your nephrologist get a more accurate picture of your kidney function.

According to Dr. Cavanaugh, decreasing proteinuria is generally associated with better long-term kidney outcomes. So, many C3G treatments are designed with that goal in mind.

Still, your uPCR doesn’t tell the whole story. It’s one of many data points your nephrologist needs to collect and compare over time to know how active the disease is.

What causes your numbers to change?

Your uPCR can fluctuate for lots of reasons, and not all of them are cause for concern.

“Proteinuria test results can be incredibly varied,” Dr. Cavanaugh notes. “They can range 50% one way or the other from test to test.”

An increase in your uPCR may signal that your disease is progressing. Or it could reflect scarring in the filtering units of your kidneys, called glomeruli, from a previous flare. This damage to the filtration barrier, called glomerulonephritis, causes more protein to leak into your pee.

But it can also go up or down because of:

• The time of day
• How hydrated you are
• How concentrated your pee is
• Blood pressure fluctuations
• Your diet
• Your activity levels
• Your stress levels
• An illness or infection

And sometimes, it’s none of the above.

Your uPCR could be higher because the urine sample was contaminated, you have a UTI, you’re a little dehydrated — the list goes on. That’s why it’s important that your test results are interpreted by a specialist in glomerular diseases.

It’s also why you need kidney function tests so often. A single data point isn’t enough — your nephrologist determines how well your kidneys are doing based on trends over time.

If your uPCR is trending upward, your provider needs to figure out why and what, if anything, to do about it. For example, if the increase is due to scarring from a prior flare-up, changing your C3G treatment plan won’t make a difference.

“The challenge is knowing what’s actionable,” Dr. Cavanaugh says. “We have to treat every situation differently.”

When to get help

uPCR testing usually happens in your doctor’s office or at a lab. It’s not something you usually do on your own.

In other words, your provider typically contacts you if there’s cause for concern. And that’s a good thing because changes in your kidney health aren’t always noticeable.

“I sometimes have to convince someone that they have a problem,” Dr. Cavanaugh shares. “They may be feeling well, but I’m telling them, ‘There’s protein in your urine, and we really need to focus on that.’”

But you’re more than your uPCR. And other symptoms can be telling, too. Reach out to your provider if you notice:

• Worsening fatigue
• Increased swelling (or unexplained weight gain)
• Changes to the color or consistency of your urine
• A change in how much (or how often) you pee
• Shortness of breath

These changes aren’t always a sign that something’s wrong. But they are a reason for your nephrologist to investigate further.

Stay engaged in your care

All the testing involved in C3G monitoring can get frustrating, especially if your lab results don’t seem to match the way you feel, or if your numbers fluctuate for no clear reason.

That’s why Dr. Cavanaugh says it’s important to have a good relationship with your provider.

“When your nephrologist tells you that you have more or less protein in your urine than before, you need to be able to trust them enough to follow their lead and take the therapeutic steps they’re suggesting,” he emphasizes.

But if you’ve been living with C3G for a long time, trust may be in short supply.

“Nephrologists used to have to tell people with C3G that there was nothing that could be done for it,” he recounts. “We told them, ‘Stick around. In 10 years, things could change.”

It was a big ask with little reward, he notes, so many people with C3G checked out. But if you fit in that category, Dr. Cavanaugh hopes you’ll re-engage.

“The last two or three years have been huge for C3G research,” he encourages. “There are therapies for you now — therapies that really work. And the last thing we want is for you to miss out on them.”