Understanding complement 3 glomerulopathy (C3G)

Complement 3 glomerulopathy (C3G), is a rare kidney disease that affects how the kidneys remove waste, excess fluid and minerals from the blood. When kidneys lose their filtering abilities, dangerous levels of fluid and toxins build up in the body.

C3G is classified as a glomerular disease — conditions that affect a specific part of the kidney called glomeruli. Glomeruli are the tiny network of blood vessels in the kidneys that filter waste and remove extra fluids from blood. When glomeruli are damaged and don't function properly, it's classified as a glomerular disease.

To better understand C3G, it's helpful to know what each part of its name stands for.

Complement: The "C" stands for the body's complement system. This system is a group of proteins in the blood that complement, or help, the immune system fight pathogens such as bacteria and viruses.

C3: C3 is a specific protein that's part of the complement system.

Glomerulopathy: A set of diseases affecting the glomeruli in the kidneys.

C3G is considered a disease of a poorly regulated complement system. In C3G, the complement system becomes overactive. When this happens, too much C3 is broken down into smaller components that get trapped in the kidneys and damage the glomeruli. This causes inflammation and scarring that affects how the kidneys remove toxins from the blood.

The longer this activity continues, the more kidney damage occurs. Eventually, this can lead to kidney failure that requires dialysis, a process where the blood is filtered with a machine, or a kidney transplant.

In general, C3G can affect people of all ages, including children and young adults — although the signs and symptoms may not begin until adulthood. In some cases, the disease develops after an upper respiratory tract infection, including streptococcal infections such as strep throat.

C3G causes many of the signs and symptoms of other glomerular diseases, including:

• Cola- or tea-colored urine — caused by red blood cells in the urine.
• Visible blood in the urine or red blood cells detected in a urine test that can only be seen with a microscope.
• Urine that looks foamy or bubbly — from protein leaking into the urine.
• Swelling in the hands, feet and ankles.
• High blood pressure.
• Fatigue.
• Gradual or rapid loss of kidney function — measured with a blood test and other tests that determine how well the kidneys are removing waste and excess fluid from the blood.

In addition, C3G can cause symptoms that may not be related to kidney function, including:

• Vision problems caused by a buildup of protein in the retina, the light-sensitive part at the back of the eye.
• Uneven distribution of fat under the skin. Some areas on the body will appear thin — where there is a lack of fatty tissue. Other areas might appear larger — where extra fat is located.

C3G affects everyone differently. For some, the disease slowly develops over many years. Sometimes, the disease progresses much more quickly, causing end stage kidney disease, also called kidney failure.

There isn't a cure for C3G. Your doctor will create a treatment plan that is best for you and your individual circumstance. Treatment aims to slow down the pace at which the disease develops and to reduce symptoms.

Treatments to slow the process of kidney damage include:

• High blood pressure medications. Taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) can lower blood pressure and reduce protein loss.
• Immunosuppressants and corticosteroids. These medications calm the immune system and stop it from attacking the glomeruli. Other potential treatment options include mycophenolate mofetil, cyclophosphamide or eculizumab.
• Statin therapy. If you have high cholesterol, cholesterol-lowering medications can help control it and slow the progression of kidney damage.
• Diuretics. These remove extra fluid from the blood. Removing extra fluid can help improve blood pressure control.
• Novel therapies. There is current research and heightened interest in using medicines that inhibit the complement system to effectively treat C3G.

Your health care team may recommend diet changes, such as reducing salt (sodium) and protein to decrease the burden on the kidneys. The goal of treatment is to avoid the need for kidney dialysis or a kidney transplant. But in some cases, dialysis or transplantation is necessary.