Complement 3 Glomerulopathy

Complement 3 glomerulopathy (C3G) is a disease in which the immune system attacks and damages the kidneys. Specifically, tiny filters inside the kidneys called glomeruli become inflamed and damaged by immune proteins called C3 complement. C3G can be caused by gene mutations (changes) that are present in your DNA from birth. It can also develop over time, like many other autoimmune conditions, where autoantibodies attack our own tissue.

Many of the symptoms of C3G overlap with the general symptoms of chronic kidney disease, since this disorder also leads to worsening kidney function. However, C3G can also cause non-kidney-related symptoms like eye problems. C3G can only be diagnosed for sure by doing a kidney biopsy. To diagnose C3 glomerulopathy, your doctor must check the biopsy for the presence of C3 complement proteins in the glomeruli.

IgA Nephropathy

IgA Nephropathy (IgAN) is an autoimmune disease where antibodies — immune proteins — build up in your kidneys. It’s also called Berger’s disease. When antibodies build up, they can cause inflammation and activate white blood cells to attack.

In IgAN, IgA antibodies build up in your kidneys, clogging the filters and causing kidney damage. IgAN is one of the most common causes of kidney disease affecting the glomeruli, but it often doesn’t cause symptoms for many years. In most people, it’s not clear what causes IgAN. It sometimes runs in families, but most people with IgAN don’t have a family history of the disease.

Some of the early symptoms of IgA nephropathy include:

• Pink or dark-colored urine, especially after a cold or other infection
• Blood in your urine
• Foamy urine, caused by too much protein
• Swelling in your hands and feet

Like other rare kidney diseases, you need a kidney biopsy to be sure of a diagnosis. If the biopsy shows IgA protein buildup, you may have IgAN.

Focal Segmental Glomerulosclerosis

In focal segmental glomerulosclerosis (FSGS), scar tissue forms on the glomeruli, decreasing kidney function. This condition is rare, affecting about seven people per million every year. FSGS can be caused by an inherited gene mutation or other conditions like diabetes and certain infections. However, many people with FSGS have no known cause for their condition. One specific symptom of FSGS is swelling in your legs. Lab tests may also show signs like proteinuria (protein in your urine) and low protein levels in your blood. A kidney biopsy is needed to confirm FSGS.

Fabry Disease

Fabry disease is a disorder in which the body does not make enough of a specific protein. This protein, called alpha-galactosidase A (alpha-GAL), breaks down a fatty substance called globotriaosylceramide (GL-3). When alpha-GAL levels are low, GL-3 builds up in your kidneys and causes damage. Fabry disease is caused by a gene mutation and is passed down in families. Because it’s very rare, it’s often misdiagnosed or just missed altogether.

The signs and symptoms can vary but may include:

• Protein in your urine
• Reduced kidney function (leading to a possible diagnosis of CKD)
• Pain, tingling, or burning in your hands and feet (one of the most common symptoms)
• Red-purple spots on your skin
• Unusual patterns on the cornea (outer layer of your eye), which an eye doctor can diagnose

If you have any of these unusual non-kidney-related symptoms along with kidney issues, consider asking your healthcare team about testing for Fabry disease. A diagnosis can be confirmed with a genetic test for the mutation that causes the condition.

How Are Rare Kidney Diseases Treated?

There are several types of medications that are often prescribed for people with rare kidney diseases, some of which are described above. Although none of these conditions has a cure, treatment focuses on slowing kidney damage and reducing its effects on other organs, like the heart.

Depending on which rare type of CKD someone has, doctors may recommend a combination of:

• Blood pressure medications to reduce blood pressure and the amount of protein lost in urine, such as ACE inhibitors
• Immune-suppressing medications such as glucocorticoids (also called steroids) because many of these conditions cause inflammation in the kidneys or have autoimmune causes
• Diuretics, known as water pills, to reduce swelling

For some conditions, like C3G, specific treatments like complement inhibitors have been developed to block the immune system proteins that cause the disorder. If you receive a confirmed diagnosis, your healthcare team can discuss the best treatment options with you.

How Do You Know if You Have a Rare Kidney Disease?

Many rare kidney disorders require extra testing to diagnose. A kidney biopsy or genetic testing is often needed to be certain which type of CKD you have. If you’re unsure about your CKD diagnosis, reach out to your healthcare team. You can ask them to explain your diagnosis again and review your test results together to get a clearer understanding. You can also ask if they’ve specifically tested for rare kidney conditions that could be causing your symptoms. If a rare kidney disease is suspected, it is better to have a nephrologist (kidney specialist) and probably a rare disease specialist on your healthcare team.

Since diagnosing rare kidney disease is challenging, getting a second opinion from another provider can be very helpful. If your treatment plan isn’t working for you, or you feel like your CKD symptoms are getting worse, a second opinion is especially important. Another provider might have the experience to catch a rare condition that initially went undiagnosed.

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