Rare Disease Day: Rare kidney diseases you may not know about

February 28 (or for Leap Year, February 29) is Rare Disease Day, dedicated to spreading awareness of the 300 million people worldwide and 30 million Americans living with a rare disease, as well as their families and caregivers. This includes all the Americans living with one of the more than 150 rare kidney diseases. 

The top two causes of kidney disease are diabetes and high blood pressure. However, many other things can also cause kidney disease and kidney failure, including rare diseases. According to the National Organization for Rare Diseases (NORD), a disease is considered rare if it affects fewer than 200,000 people in the United States. Approximately 72% of rare diseases are genetic and 70% of rare diseases begin in childhood.  

Unfortunately, many people with rare diseases — including kidney diseases — struggle to get an accurate diagnosis and treatment. For kidney disease, these delays can mean someone doesn't know they have kidney diseases until it has progressed to kidney failure, which requires dialysis or a kidney transplant to live.

AKF is committed to improving our understanding of rare diseases, from providing educational resources to continuing its leading efforts related to our Unknown Causes of Kidney Disease (UCKD) Project launched in 2020. The UCKD project began as a result of hearing from many patients who lived through the struggles of obtaining a diagnosis for rare and genetic kidney diseases.  

In honor of Rare Disease Day, here are some rare kidney diseases you may not know about. You can find more information about each of these diseases on the website pages linked in the name.

Atypical hemolytic uremic syndrome (aHUS)

More commonly called aHUS, atypical hemolytic uremic syndrome is a very rare genetic disease that causes tiny blood clots to form in your blood vessels. The clots block blood flow to important organs, including the kidneys. 

Alport syndrome

Alport syndrome is a genetic disease caused by problems with three genes that control the way certain parts of your body are shaped. When there are problems with these genes, parts of your kidneys, ears and eyes do not grow correctly. Alport syndrome can cause hearing loss and eye problems, but it always causes kidney disease. 

Amyloidosis

Amyloidosis causes proteins called amyloids to build up and form clumps inside your organs and tissues. These clumps can cause damage to those organs, which include the kidneys, heart, brain, liver and intestines. There are two types of amyloidosis that often affect the kidneys: primary amyloidosis and dialysis-related amyloidosis. Primary amyloidosis can cause kidney disease. Dialysis-related amyloidosis can happen by being on dialysis for a long time. Fortunately, both types of amyloidosis can be treated.

APOL1-Mediated Kidney Disease

APOL1-mediated kidney disease (AMKD) is actually a spectrum of kidney diseases associated with variants (mutations) in the apolipoprotein L1 (APOL1) gene. Everyone has two copies of the APOL1 gene, but people with two mutations are at higher risk of developing genetic forms of kidney disease. They are also more likely to have kidney disease that progresses to kidney failure much faster than for people who do not have the APOL1 gene mutations. 

People who have Western and Central African ancestry are at an increased risk of having a mutation in one or both of the APOL1 genes. The discovery of the APOL1 gene variants is very recent — in the last 20 years — so awareness of it is low. To spread awareness of AMKD and help people understand their risk for the condition, AKF is launching the first annual AMKD Awareness Day on April 30, 2024. Find out more about AMKD Awareness Day — including how you can get involved.

Complement 3 glomerulopathy (C3G)

Complement 3 glomerulopathy (C3G) is a type of kidney disease related to improper function of the immune system, which is your body's cells and tissues that fight infection. With C3G, a part of the immune system called the complement system becomes overactive and doesn't work properly, leading to damage and inflammation in the kidneys. Specifically, it damages the glomeruli, which help the kidneys filter toxins out of the blood. This damage prevents the kidneys from filtering toxins out of the blood and can cause kidney failure in about half of adults who are diagnosed with the disease. C3G can be caused by genetic changes in certain proteins or by autoantibodies — which are abnormal proteins that can also change the ability of proteins to control the complement system.

Cystinosis

Cystinosis is a rare, multisystem genetic disease that accounts for nearly 5% of all childhood cases of kidney failure, although some people with cystinosis do not develop kidney disease until they are teens or adults. Caused by mutations in the CTNS gene, cystinosis happens when cystine, a component of protein, builds up in your body's cells. Having too much cystine causes cell death and can damage your organs including your kidneys, eyes, pancreas, liver and brain. 

Fabry disease

Fabry disease is a rare genetic disorder that means your body does not make enough of an enzyme (which are proteins that speed up the chemical reactions in our bodies) called alpha-galactoidase A (alpha-GAL). Alpha-GAL helps break down and remove a fatty substance found in your cells (called globotriaosylceramide or GL-3). Without enough alpha-GAL, the fatty substance builds up in cells throughout the body, which can cause damage to organs like the kidneys, heart and brain. Fabry disease can be difficult to diagnose and is often mistaken for other more well-known diseases. 

Focal segmental glomerulosclerosis (FSGS)

Focal segmental glomerulosclerosis (FSGS) is a rare type of glomerular disease that causes scarring (sclerosis) in your kidneys. Scarring in FSGS occurs on the tiny filters in your kidneys (glomeruli) that help remove toxins from your blood. Only some parts of some filters are scarred when you have FSGS, but the damage can still lead to kidney disease or even kidney failure. The cause of FSGS is unknown, but there are some health problems that are thought to cause FSGS including (but not limited to) diabetes, sickle cell disease and lupus. 

Granulomatosis with polyangiitis (GPA)

Granulomatosis with polyangiitis (GPA) is a rare disease of the blood vessels that used to be called Wegener's granulomatosis. It causes inflammation or irritation in the vessels which makes it harder for blood to flow through the vessels. This lowers the amount of blood reaching your organs like your lungs and kidneys and when organs do not get enough blood, it can damage them. GPA can get worse quickly and it is important to treat it early to prevent permanent organ damage, such as kidney failure. 

Hemolytic uremic syndrome (HUS)

Hemolytic uremic syndrome (HUS) occurs when your red blood cells are destroyed and block your kidneys' filters. HUS is most often caused by infection with the E. coli bacteria, but it can also be caused by other bacteria and viruses and some medicines, or from an inherited gene mutation. This disease usually happens suddenly in children, and the first symptoms can seem like those of a stomach virus. As the infection continues, HUS can become more serious and can cause acute kidney injury, leading to kidney disease or kidney failure.

Henoch-Schönlein purpura (HSP)

Henoch-Schönlein purpura (HSP), also known as anaphylactoid purpura, causes small blood vessels in your body, including those in the skin, stomach and kidneys, to become swollen and leak. HSP happens more in children than in adults and can become active in flare-ups throughout the course of your life.

IgA nephropathy (IgAN)

IgA nephropathy (IgAN), also known as Berger's disease, is an autoimmune disorder. In other words, it is a type of kidney disease related to improper function of your immune system, which is your body's cells and tissues that fight infection. IgAN causes your immune system to produce abnormal antibodies in your kidneys, which triggers inflammation and reduces the kidneys' ability to filter waste and fluid from the bloodstream. This causes damage to the kidneys and can eventually lead to kidney failure. 

Lupus nephritis

Lupus is an autoimmune disease. An autoimmune disease means your immune system does not function properly, impacting your body's ability to fight infection. It can also cause your immune system to attack your healthy cells. When your immune system attacks your kidneys, it is called lupus nephritis. The most severe kind of lupus nephritis is proliferative nephritis, which can cause permanent damage to your kidneys. Many experts believe the cause of lupus is a combination of genetic and environmental factors. Only people who have lupus can develop lupus nephritis. The two main risk factors are sex and race/ethnicity with men and people of color (including Black, Hispanic/Latino and Asian American people) at a higher risk of developing the disease. Get Looped In on Lupus Nephritis and find out more. 

Minimal change disease

Minimal change disease (MCD) is a condition that damages the tiny filters in your kidneys (glomeruli) that clean your blood. This can lead to kidney disease or kidney failure. MCD is called "minimal change" disease because the damage to the blood vessels is too small for doctors to see even with a regular microscope — so they must use a powerful device called an electron microscope. MCD can happen in people of all ages, but it is more common in children than in adults.

Primary hyperoxaluria

Primary hyperoxaluria (PH) is a genetic liver disease that can cause kidney stones and kidney damage. The liver is an organ that converts everything you eat or drink into nutrients and gets rid of toxins. If you have PH, your liver does not make enough of a certain protein to prevent a natural chemical found in plants and your body called oxalate from building up in your body. When too much oxalate builds up, your kidneys cannot remove it all and that can create kidney stone and calcium oxalate crystals. Over time, those can damage your kidneys and cause kidney disease.

Polycystic kidney disease (PKD)

Polycystic kidney disease (PKD) is the result of a change in your genes (a genetic mutation) that causes cysts (fluid-filled growths) to grow inside your kidneys. There are two forms of PKD: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). The former is more prevalent with about 9 out of 10 cases of PKD being ADPKD. ARPKD primarily affects infants and children, with approximately 1 in 25,000 children living with ARPKD, according to the PKD Foundation. Find out additional facts about PKD in this blog post. 

Again, there are over 150 rare kidney diseases, so this list is not a full one. In addition to rare diseases, AKF is also interested in raising awareness about kidney disease and kidney failure that has no known cause, another reason why we created the Unknown Causes of Kidney Disease Project. According to the U.S. Renal Data System, about 5% of kidney failure cases are due to unknown causes and in a AKF survey, health care providers said they estimated 15% of their patients have kidney disease with no known cause. 

Find out more about the types of kidney diseases and other kidney problems or find out how you can participate in Rare Diseases Day.