Shall we talk about a rare disease called C3G (Complement 3 Glomerulopathy), which affects the kidneys?

Do you sometimes experience blood in your urine, or swelling in your legs? Or do you feel tired all the time? These can sometimes be due to a problem with your kidneys. Today we are going to talk about a rare but very important condition that affects the kidneys. That is C3G (C Three G) or ``Complement 3 Glomerulopathy``.

What is C3G (Complement 3 Glomerulopathy)?

Simply put, C3G is a group of diseases that affect how well your kidneys work. You know, the kidneys are like the two filters in our bodies. Their main job is to filter the blood, remove unnecessary waste products and excess water, and make urine.

"Complement 3" is a special protein in our blood. It is very important for the immune system that fights against diseases in our body. "Glomerulopathy" is damage to the glomeruli, which are tiny blood vessels inside the kidneys, which are like little meshes. These glomeruli are the ones that filter the blood.

Then C3G is a disease that involves the `complement 3` protein, damaging the `glomeruli` and impairing the functioning of the kidneys. In the past, that is, before 2013, doctors called this ``Membranoproliferative glomerulonephritis (MPGN) type I, II or III`` or ``Mesangioproliferative glomerulonephritis``. But now this group of diseases is called C3G.

Are there types of C3G?

Yes, there are two main types of C3G. Doctors determine these two types by taking a small piece of the kidney (we call it a `kidney biopsy` ) and looking at it under a microscope, based on the damage and inflammation to the `glomeruli`.

• Dense deposit disease (DDD): Previously known as MPGN type II, this condition is characterized by the formation of dense, ribbon-like deposits in the glomerular basement membrane (GBM), the lining of the glomeruli. It most commonly affects children and young adults in their early 20s.

• `C3 glomerulonephritis` (C3GN): Previously called `MPGN type I` or `III`. In this, the dense deposits like those seen in DDD are not visible. This mostly affects people over 30 years of age.

Is C3G a chronic disease?

Yes, C3G is a chronic disease. This means that it is not something that will suddenly develop and get better, and the damage to the kidneys can increase over time. Therefore, it is very important to be careful about this.

How common is this C3G?

This is actually a very rare disease.Doctors estimate that this occurs in about two to three people per hundred thousand. So you may not have heard much about it. But even though it's rare, it's important to be aware of it.

What are the symptoms of C3G disease?

Now let's see what the symptoms of this C3G disease are. Both types have several common features, which are important to recognize:

• Blood in the urine ( hematuria ): Sometimes the urine may appear red, or it may be a small amount that can only be seen under a microscope.
• Excess protein in the urine (proteinuria): This can cause the urine to appear foamy.
• Passing less urine than normal (oliguria).
• Decreased protein levels in the blood (hypoalbuminemia).
• Swelling (edema): Especially in the hands, ankles, and feet. Imagine, if you wake up in the morning and your feet feel swollen, it could be something like this.
• High blood pressure (hypertension).
• Recurrent infections.
• Feeling very tired (`Fatigue`): Not just tiredness, but a feeling of being exhausted no matter how much sleep you get.
• Some people may develop conditions like gout .

Both of these symptoms can lead to kidney failure . Kidney failure can also cause symptoms such as:

• Always tired.
• Nausea, vomiting.
• Difficulty in making up one's mind, desperation.
• Body swelling.
• Passing more urine than usual (this can sometimes be seen in the early stages of kidney failure).

In addition to the kidneys, C3G can also cause other symptoms. These include:

• Vision problems: Vision can be impaired due to the accumulation of protein and calcium deposits (drusen), especially in the macula.
• Lipodystrophy: This is a condition in which fat is lost in certain areas of the body (especially the face and limbs).

Why is this C3G formed?

Okay, now let's see why this C3G is formed. This is a little complicated, but I'll explain it simply. This happens when the ``complement system`` in our body is not working properly. This ``complement system`` is a collection of proteins in our blood. This is part of our immune system. This helps fight things like bacteria and viruses that come from outside.

What happens to someone with C3G is that this `complement system` is activated too much, or out of control. Then the `complement 3 (C3)` protein gets damaged. These damaged C3 protein fragments get stuck in the `glomeruli`. Then it becomes difficult for the `glomeruli` to filter blood and make urine. If left untreated, this damage can continue and lead to kidney failure.

Often, it's hard to pinpoint the exact reason why this ``compliment system'' goes haywire. But sometimes:

• C3G can develop due to changes in our genes (mutations in genes related to the complement system, such as ``C3`` and ``CFH``).
• A blood disease called ``Monoclonal gammopathy`` can also indirectly damage the kidneys, disrupt the functioning of the ``complement`` system, and lead to the formation of C3G. This ``monoclonal gammopathy`` is a condition that affects the plasma cells in our bone marrow.
• Medical researchers suspect that something called ``autoantibodies'' may also play a role. ``Autoantibodies'' are proteins produced by our own immune system that mistakenly attack our own healthy tissues. However, there is not enough research to say for sure that these ``autoantibodies'' are the cause of C3G.

Who is most affected by this C3G disease?

This C3G disease can develop in anyone. It affects both men and women equally. The average age of diagnosis is around 23 years. However, the `DDD` type we mentioned earlier can appear at a younger age than the `C3GN` type.

What are the possible complications of C3G?

The main and most dangerous complication is that approximately 50% of people with C3G, or one in two, will develop kidney failure within 10 years of diagnosis. This is what we should all fear the most.

How is C3G disease diagnosed?

A doctor will do several tests to check the health of your kidneys and how well they are working. These may include:

• Blood tests: A small blood sample is taken from a vein in your arm and the lab checks to see if your complement proteins are normal or if there are excess waste products (e.g. creatinine) in your blood.
• `Estimated Glomerular Filtration Rate (eGFR): This is a test that measures how well your kidneys are filtering your blood, based on the amount of `serum creatinine` or `cystatin C` in a blood sample. This can give you a good idea of ​​how well your kidneys are working.
• Urinalysis: You will need to urinate into a special cup and give the sample to your doctor. The lab will check for protein or blood in the urine, which can only be seen under a microscope.
• Kidney biopsy: This is whatThe best way to definitively diagnose C3G disease is through a biopsy. In this, a doctor takes a small piece of tissue from your kidney using a fine needle or small incision and tests it in a lab. If this sample contains pieces of the damaged C3 protein in your glomeruli, it could be C3G disease. This biopsy can also tell you which type of C3G you have (DDD or C3GN), based on whether or not you have those solid deposits.

Can C3G be completely cured?

Unfortunately, there is currently no cure for C3G disease. But don't worry, doctors and researchers are continuing to study this disease and are working to find new treatments. We hope that a better treatment will come in the future.

What are the treatments for C3G?

There are currently no specific treatments approved by the U.S. Food and Drug Administration (FDA) for C3G. However, doctors can prescribe a variety of treatments and supportive care to slow the progression of C3G, control symptoms, and reduce kidney damage. These include:

• Blood pressure medications: Medications like angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) reduce the pressure inside the glomeruli. This reduces the amount of protein in the urine and reduces the strain on the kidneys.
• Cholesterol-lowering drugs: Your doctor may prescribe medications like statins to lower cholesterol and reduce damage to your kidneys.
• Dietary changes: A renal dietitian will help you develop a diet plan that is right for you and helps you maintain a healthy weight. Reducing your intake of salt (sodium), saturated fat, and cholesterol can help reduce kidney damage.
• Corticosteroids: Also known as "steroids," these are anti-inflammatory drugs that work by stopping the immune system from attacking your glomeruli.
• Eculizumab: This is a monoclonal antibody drug used to treat rare blood disorders. It may help improve kidney function by reducing protein in the urine and increasing glomerular filtration rate in some C3G patients.
• Dialysis: About 50% of people with C3G are said to have kidney failure. Dialysis is when the kidneys fail, and the work that the kidneys should do (clean the blood, remove waste products, and excess fluid) is done with the help of a machine.
• Kidney transplant: This is another treatment for kidney failure. A surgeon removes your failing kidney and replaces it with a healthy kidney from a donor.

If you have either `DDD` or `C3GN` and also have `monoclonal gammopathy`, your doctor will recommend further tests to check for other underlying conditions.

What is the outlook for C3G disease?

About half of patients with C3G develop kidney failure within 10 years of diagnosis. There is currently no cure for kidney failure. However, with an accurate diagnosis and prompt treatment, you can live a long, healthy life without major changes. Therefore, it is important to stay calm and follow your doctor's advice.

Can C3G disease be prevented?

Unfortunately, there is currently no way to prevent C3G disease, as it is often caused by factors beyond our control.

How do I take care of myself?

If you have C3G, your doctor will develop the best treatment plan for you. This may include medication, supportive care, and lifestyle changes. Your treatment plan may include the following, and it is important to follow these steps:

• Take your medicine exactly as prescribed by your doctor. Don't miss a single day.
• Changing your diet, especially reducing salt, oil, and sugar, and eating more fruits and vegetables.
• Avoid using non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., painkillers like ibuprofen and diclofenac) without medical advice, as they can damage the kidneys and accelerate kidney failure.
• Taking care of your mental health. Having such a rare disease can make you feel lonely and scared. Also, knowing that C3G can cause kidney failure increases your risk of developing depression. Talk to your doctor about your mental health and seek counseling and treatment if necessary. Ask your doctor about support groups for people with C3G. Meeting other people with C3G can help reduce loneliness and share experiences.

When should I see a doctor?

If you have symptoms of C3G, especially changes in your urine (bloody, foamy, less), swelling, or extreme fatigue, see a doctor right away. These could be signs that your kidneys are not working properly.

If you are diagnosed with C3G, your doctor will refer you to a specialist in kidney disease (a nephrologist). He/she will be the one who will give you the best treatment plan.

What questions should I ask my doctor?

When you see the doctor, don't hesitate to ask questions like these:

• How do I know for sure if I have C3G?
• If I don't have C3G, what other disease could I have?
• What type of C3G do I have (DDD or C3GN)?
• What treatments do you recommend for me? Are there any side effects?
• What changes should I make to my diet?
• Do you think my kidneys will fail? What can I do to prevent that from happening?
• Can I see a nephrologist?

Finally, I have to say...

C3G is a rare, complex disease that affects the tiny filtering units in the kidneys. If you have C3G, you may experience changes in your urine, swelling, joint pain, vision problems, and fatigue.

You may experience a variety of emotions as you accept this diagnosis and adjust to how C3G will affect your life. Don’t worry, you are not alone. Give yourself time and space to learn about C3G and your treatment options. Learning about your options and what to expect can help you deal with your feelings in a healthy and productive way. Doctors are there to provide information and guidance. If you have any questions, need advice or support, talk to them. Remember, with early diagnosis and proper treatment, you can control this disease and live a good life.

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