Complement 3 (C3) glomerulopathy is a set of rare kidney (renal) diseases that can cause a variety of symptoms. Glomerulopathy refers to the damage done to the tiny filtering units in the kidneys known as glomeruli. Your kidneys are responsible for filtering out waste and fluid. When these organs become damaged, you may start to notice changes in your urine or swelling due to fluid buildup.
Knowing the symptoms of C3 glomerulopathy can help you identify the disease sooner rather than later. Your doctor or nephrologist — kidney specialist — will develop a tailored treatment plan to help control your symptoms and reduce the chances of C3 glomerulopathy progressing to kidney failure.
C3 glomerulopathy is an umbrella term used to describe two forms of kidney disease — C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). It’s important to note that these names were introduced in 2013, so people who were diagnosed before that may know their condition as membranoproliferative glomerulonephritis (MPGN) or mesangioproliferative glomerulonephritis. These conditions are caused by abnormal activation of the complement system. The complement system is an important part of your immune system that helps protect your body against bacteria and viruses.
The complement system is made of nearly 50 proteins, including C3. When your body has an infection, this important protein is broken down to help produce inflammation and trigger other complement proteins to kill bacteria and viruses. However, activation of the complement system due to causes other than infections can be damaging. Some people have mutations in genes that help regulate this system, like brakes in a car. When these genes don’t work properly, inflammation can become uncontrollable. Another way the complement system can be overactivated is by autoantibodies, which are abnormal antibodies that can attack and affect the function of our own complement proteins.
The kidneys are especially sensitive to this inflammation. Broken-down C3 proteins can get stuck in the glomeruli, damaging them and causing scarring. This affects your kidney function by preventing the proper filtration of your blood to remove waste and fluid. Your doctor may order a blood test to measure your glomerular filtration rate, or how much blood is filtered through your kidneys every minute.
Toxins and extra fluid also begin building up, which can damage your kidneys even more. If it’s not treated in time, C3 glomerulopathy can eventually progress to end-stage renal disease and kidney failure. The only treatment options for kidney failure are dialysis or a kidney transplant.
Your kidneys are your body’s cleaning crew — they filter out toxins from your blood so these unwanted substances can be excreted in your urine. But did you know the kidneys have several other functions? These organs also maintain your body’s fluid balance, release hormones that help regulate your blood pressure, and even support your bone health.
Your kidney health has a direct impact on your overall health, so if your kidneys become damaged from C3 glomerulopathy, you may develop symptoms or notice signs that they’re not working as well as they should. Symptoms are different in everyone, and they can be mild or severe depending on the amount of damage.
For many people, symptoms aren’t noticeable until their C3 glomerulopathy has progressed to a more advanced stage. C3 glomerulopathy symptoms tend to start around the age of 30, but signs of DDD tend to show up earlier — usually in children and young adults.
It’s important to note that if you don’t have a diagnosis and you experience the issues discussed below, you’re more likely to have another kidney-related condition, not C3 glomerulopathy. This is because C3 glomerulopathy is very rare — it’s only estimated to occur in two to three people out of 1 million. However, understanding these signs and symptoms may motivate you to get an evaluation by your doctor, which could lead to a diagnosis. Whether or not that diagnosis is C3 glomerulopathy, understanding the following kidney-related issues can be an important first step.
Your urine can tell you a lot about your kidney health. If your urine appears red, pink, or brown, it may be a sign of C3 glomerulopathy. These color changes are all caused by blood in your urine, also known as hematuria. You may also notice spots of blood floating in the toilet after you urinate. It’s also possible to have a very small amount of blood in your urine that can be detected only through urinalysis (a urine test), in which a sample is looked at under a microscope or tested for different components.
Hematuria is a sign that your kidney’s filtering units are damaged. Normally, the glomeruli filter out fluid, waste, and other substances from your blood over a thin membrane. This barrier keeps proteins and blood cells from leaving your body in your urine. However, in C3G, the glomeruli are damaged, allowing blood to leak out and be excreted from your body.
Dark, foamy, or cloudy urine may be a sign that protein is leaking into your urine as well. When your kidneys filter your blood, the proteins are too big to be excreted and are returned to your bloodstream. Proteins are essential building blocks for your muscles, and they also help your body reabsorb fluid to maintain balance.
In C3 glomerulopathy, proteins can leak out of your kidneys and into your urine. This condition is known as proteinuria or albuminuria, referring to the protein albumin that can leak into urine as a result of kidney disease.
If your urine protein levels are extremely high, you may have a condition known as nephrotic syndrome. Other symptoms associated with this glomerular disease include loss of appetite, swelling, and weight gain from excess fluid buildup in your body.
Damaged kidneys can’t properly filter out wastes and toxins from your blood, causing these substances to build up. This condition is known as uremia or urea in the blood. It causes higher levels of creatinine, a waste product made by muscle cells. It also increases urea, which is made by the liver when it breaks down proteins.
Uremia may be a sign of C3 glomerulopathy. The buildup of creatinine and urea in your blood can interfere with the way your brain works, making it difficult to remember things or concentrate. Fatigue, muscle cramps, itching, and shortness of breath are also common symptoms of uremia.
As C3 glomerulopathy progresses, you may start to notice symptoms of more severe disease, including swelling. Your kidneys can’t clear out excess fluid as well as before, so the fluid begins collecting in your body.
You may notice swollen or tight-feeling skin around your hands, feet, and ankles. The skin around your eyes can also become puffy, making your lids and the area underneath your eyes look swollen.
Excess fluid buildup can put extra pressure on your blood vessels, causing high blood pressure. Also known as hypertension, high blood pressure is a common symptom of C3 glomerulopathy and other kidney diseases. It’s important to address and treat it before it damages your kidneys further.
You probably won’t notice any symptoms of high blood pressure, so it’s important to get regular checkups and screenings at your doctor’s office. Some people experience headaches, nosebleeds, or shortness of breath with high blood pressure, but only in severe cases.
Uric acid, a product made from breaking down purines (substances produced in the body and also found in certain foods and alcohol), is typically filtered out by your kidneys and excreted in your urine. In C3 glomerulopathy, your kidneys can’t remove enough uric acid, so it begins collecting in your joints and crystallizing. This is known as gout — a type of inflammatory arthritis that causes painful, swollen, hot joints.
Gout typically affects one joint at a time, most often the big toe. Gout is a condition with periods of worsening symptoms (flares) and periods of relief (remission). Flares can last several days to weeks, depending on how severe your case is.
If you’ve noticed new symptoms of C3 glomerulopathy or if they’ve become worse recently, talk to your healthcare provider or nephrologist. It’s important to keep your provider updated on your symptoms not only at your first appointment but also at every visit.
Worsening symptoms may be a sign that your current treatment plan isn’t as effective as it should be. Your doctor or nephrologist may change one or more of your medications to better manage your symptoms and prevent C3 glomerulopathy from progressing into more severe kidney disease.
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