Primary hyperoxaluria and oxalate: Symptoms, causes and treatment

What is primary hyperoxaluria (PH)? 

Primary hyperoxaluria (PH) is a group of rare genetic conditions where the liver makes too much of a substance called oxalate. Oxalate is a natural chemical that your body produces and is also found in some foods. Normally, your liver helps break down substances so they can safely leave your body. But in people with PH, the liver doesn't make enough of a specific enzyme or the enzyme doesn't work properly. As a result, too much oxalate builds up in the body. 

When there's too much oxalate, it can combine with calcium to form crystals. These crystals can lead to kidney stones, and over time, can damage the kidneys. In some cases, this can cause kidney failure also called end-stage renal disease (ESRD) or end-stage kidney disease (ESKD).

What causes PH and who can get it?

PH is a genetic condition, which means it's passed down through families. It happens when there are changes (mutations) in specific genes that affect how the liver processes certain substances. These changes cause the liver to make too much oxalate. If you have a blood-related family member with PH, you are more likely to have PH or carry a mutated gene that causes it. To have PH, a person needs to inherit a copy of the changed gene from each parent. If someone has only one copy of the gene, they won't have PH, but they can pass it on to their children. These people are called carriers.

If both parents are carriers, there is a:

    •    25% chance the child will have PH

    •    50% chance the child will be a carrier

    •    25% chance the child will not have PH and will not be a carrier

PH can affect people of all ages, even babies and young children, although the symptoms and severity can vary from person to person.

How does PH cause kidney disease?

Your kidneys remove oxalate from your body through urine (pee). When oxalate levels are high, the extra oxalate combines with calcium in your kidneys to form kidney stones and calcium oxalate crystals in your urine. Over time, kidney stones and crystals can damage your kidneys, making it harder for them to work properly and potentially leading to kidney failure.

When your kidneys stop working, oxalate can't leave the body in urine. Instead, it builds up and spreads to other parts of the body. This is called oxalosis. It can cause problems with your bones, blood, heart, eyes.

What are the symptoms of PH?

Symptoms can begin at any age — even in babies — but often start in childhood or teenage years. Some people don't notice symptoms until they are adults or until their kidneys are already damaged. Common signs include:

• High levels of oxalate
• Urinary tract infections (UTIs)
• Blood in your urine (your pee may look pink or red)
• Burning or pain when you pee
• Kidney stones which often cause pain in the back or side. Many people with PH begin developing stones in childhood, and most will have had stones by their early 20s. These stones may come back over time.
• Not growing properly as a baby
• Crystals found in kidney tissue (nephrocalcinosis)
• Tiredness or swelling, especially in the legs, ankles, feet, face or hands (signs of kidney failure)

If you have kidney stones, you might also feel:

• Sharp pain in your back, side, lower belly or groin
• Pain when urinating
• Sharp pain in your belly, back, or groin
• Blood in your urine (your pee may look pink or red)
• Feeling like you need to pee more than usual
• Nausea or vomiting
• Chills or fever

Your doctor may also find high levels of oxalate or frequent urinary tract infections during testing, which can be signs of PH.

How will I know if I have PH?

If you've had kidney stones — especially more than once — or have any of the symptoms above, it's important to talk to your doctor and other healthcare professionals. Your doctor may do certain tests to check for PH which include:

• Urine tests: to measure the levels of oxalate and glycolate or look for crystals, may also have blood in your urine
• Blood tests: to check oxalate levels and how well your kidneys are working
• Genetic (DNA) tests: to see if you have changes in the genes that cause PH (AGXT, HOGA1 and GRHPR genes)
• Imaging tests: to look at your kidneys, such as an x-ray, CT scan or ultrasound
• Liver or kidney biopsy: In rare cases, you may have a procedure where your doctors take a small piece of your kidneys and/or liver to look at it closely under a microscope

These tests can help your doctor and healthcare team decide which treatment is best for you. Finding out you have PH early can help you take steps to protect your kidneys and avoid serious complications. With the right care, you can help prevent kidney stones and calcium oxalate crystals in your urine, which is why early diagnosis and treatment are very important. 

Some people may not find out they have PH until their kidneys stop working and they need dialysis.  Getting a diagnosis for a rare kidney disease can be challenging, but you are the most important advocate for your health. This means asking questions, seeking second opinions when necessary and pushing for the care and treatments you need.

What are the types of PH?

There are three types of PH, they include:

• Type 1 (PH1): the most common type of PH, making up 8 out of 10 of diagnosed cases of PH. PH1 is the most severe PH type and people with PH1 are at the highest risk of kidney failure. PH1 is caused by a mutation in the gene called AGXT. This prevents your liver from making enough of the enzyme called alanine-glyoxylate aminotransferase (AGT).
• Type 2 (PH2): this type is less common than PH1. Progression to kidney failure is slower in people with PH2. PH2 is caused by a mutation in the gene called GRHPR. This prevents your liver from making enough of the enzyme glyoxylate/hydroxypyruvate reductase (GR/HPR).
• Type 3 (PH3): this type is less commonly diagnosed than PH1. PH3 is caused by a mutation in the gene called HOGA1. This prevents your liver from making enough of the protein 4-hydroxy-2-oxoglutarate aldolase (HOGA). People with PH3 are at the lowest risk of kidney failure but may experience kidney issues, like recurring kidney stones.

How do doctors treat PH?

The goal of treatment is to lower the level of oxalate in your body, slow the damage to your kidneys and delay progression to kidney failure. It is important to work with your healthcare team to follow a management plan and make healthy life changes which may be able to help prevent further damage to your kidneys or slow your disease progression. Your doctors will work with you to make a treatment plan depending on the severity of your disease. If you have PH, your doctor may prescribe you these medicines to help your liver make less oxalate:

• Lumasiran (approved for PH1)
• Nedosiran(approved for PH1)
• Vitamin B6 (pyridoxine): May be helpful for some people with PH1, depending on their genes. 

Your doctor may also recommend:

• Medicines that may help lower calcium oxalate crystal buildup, such as potassium citrate or neutral phosphorus.
• Drinking plenty of fluids (usually 8–12 cups a day) to help prevent kidney stones and oxalate buildup. Note: If you have kidney disease and need to limit fluids, ask your doctor how much you should drink each day.
• Reducing sodium (salt) in your diet to help lower calcium excretion in your urine and prevent kidney stones.
• Limiting the amount of animal protein you eat, like chicken, fish and beef, which can increase oxalate levels.
• Adding foods high in calcium, such as milk, yogurt and cheese to help oxalate from being absorbed.
• Limiting foods high in oxalate (like spinach, rhubarb and nuts)

Make sure to work with your doctor or dietitian before making any changes to what you eat. 

In serious cases, a liver and kidney transplant may be needed. This is currently the only cure for PH1. The liver transplant corrects the problem that causes extra oxalate, and the kidney transplant replaces the damaged kidney. If your kidneys have failed due to PH1, you may need to start dialysis or talk to your doctor about a combined liver and kidney transplant.  Learn more about preparing for a kidney transplant.  

Talk with your doctor and healthcare team about what treatment options are the best for you. Ongoing research and clinical trials are being conducted to test new treatments for all types of PH. These treatments may be FDA approved and available for prescription in the future. It's important to stay on top of your treatment plan, including medicines and appointments. Work with your doctor on how you can best manage your care. 

What is Enteric Hyperoxaluria (EH)?

Enteric Hyperoxaluria (EH), also known as Secondary Hyperoxaluria is a condition where too much oxalate is absorbed from food in the digestive system (gut). It happens because of problems in the intestines, like inflammatory bowel diseases (IBD), such as Crohn's disease, or conditions like celiac disease, cystic fibrosis, or chronic pancreatitis. Some types of weight-loss surgeries, like gastric bypass, can also increase the risk of developing EH. This type of hyperoxaluria is more common than primary hyperoxaluria.

Symptoms of EH may include:

• Digestive problems (gastrointestinal symptoms)
• Frequent kidney stones
• Chronic kidney disease or kidney failure
• Poor absorption of nutrients from food or unintended weight loss

To help manage EH, your doctor may recommend drinking plenty of water, eating a balanced diet with lower oxalate foods, and taking certain supplements like calcium to help reduce oxalate levels. Medicines with citrate and probiotics may also be used to help manage oxalate buildup and protect the kidneys. 

If you have a kidney stone or kidney failure, your doctor will talk with you about ways to treat them.

What kind of doctors treat PH?

If you or your child has PH, you'll likely work with a team of doctors who understand this rare condition and can help manage it. Here are some of the specialists who may be part of your care:

• Nephrologists – kidney doctors that take care of your kidneys, monitors kidney function, and manages things like kidney stones or kidney failure
• Urologists – doctors who treats problems with the urinary system and can help with kidney stones
• Geneticist or Genetic Counselors – since PH is a genetic condition, they can confirm the diagnosis and help you understand what it means for your family
• Dietitians – nutrition experts that help with food and fluid choices to support kidney health.
• Pediatric team – child-focused doctors that help guide care for kids with PH
• Transplant team - group of medical professionals who evaluate you to decide if you qualify for a transplant and medical care before and after the transplant

Where can I learn more about PH?

Taking charge of your health starts with having the right information. Learning more about your rare disease can help you feel empowered to make informed decisions and advocate for the best care.

There are trusted resources about PH available, including patient organizations, medical experts, and support groups where you can connect with others who have a rare disease and understand your journey.

Remember you are not alone – by staying informed and working with your doctor, you can take proactive steps to manage PH and protect your health.

This content was developed in partnership with the Oxalosis & Hyperoxaluria Foundation.