What is hyperoxaluria?

What is Primary Hyperoxaluria?

Primary Hyperoxaluria (PH) is a group of genetic conditions, this means that the conditions are caused by a change in your DNA and are often passed on in families.

These are rare conditions (around 4 people in a million).

Because it is so rare it can take a while to find the diagnosis.

PH happens because a substance called oxalate builds up in the kidneys.

Oxalate is made from a chemical called glyoxylate, usually this is very controlled so that only a small amount of oxalate is made. In a person with PH, the enzymes from the liver that control how much oxalate is made do not work normally. This means there is too much oxalate in the body and the body cannot get rid of it all. When there is too much oxalate in the body it makes solid crystals together with calcium.

Primary Hyperoxaluria (PH) is associated with genetic conditions. A genetic condition is caused by one or multiple changes in the DNA. These changes can be inherited or can happen during cell division. Having those genetic conditions is rare. Only roughly 4 people in a million show these genetic changes. Because it is so rare, an early diagnosis is difficult.

Primary Hyperoxaluria causes high oxalate levels in the blood.

Endogenous oxalate (aka oxalate in the body) comes from a substance called glyoxylate. Glyoxylate is broken down by an enzyme from the liver. Normally, this enzyme is regulated and only produces small quantities of oxalate. In a patient with primary Hyperoxaluria, this enzyme is malfunctioning, leading to an uncontrolled production of oxalate.

The body is now overloaded with oxalate and struggles to remove it from the body. Excessive amounts of oxalate build up in the kidney. Here they react with calcium and form crystalline structures which are the cause of kidney stones.

How does it affect people?

• Primary Hyperoxaluria (PH) mainly affects the kidneys.
• You might notice severe pain in the back or sides or tummy along with feeling feverish and you might see blood in the urine. These symptoms are because of kidney stones.
• You might also find it painful to wee, or it might feel difficult to pass urine or the urine can be cloudy.
• You can also have kidney stones without feeling anything and they can be picked up a scan which was done for a different reason.
• Children with PH might grow more slowly.
• If PH is diagnosed in babies or young children, it is usually more severe. Children are likely to have growth problems and might have anaemia which will make them tired a lot.
• Most people with PH will develop kidney stones before the age of 20 but there are a lot of differences between what symptoms people with PH get. Some people will have no symptoms and some may get a lot of pain from having kidney stones often. It is even possible for people in the same family to have very different symptoms.
• As well as kidney stones, PH can result in additional damage to the kidneys and eventual bone fractures.

What can be done?

• Everyone is different and it is always important to talk to your own doctor
• Most patients will be advised to drink lots of water (>3L/day)
• Eating a low oxalate diet can help (see our diet page here)
• Pyridoxine (vitamin B6) will be helpful for some patients but not everyone
• There is a new treatment for primary hyperoxaluria called Lumasiran, this medication is an injection which stops the liver producing so much oxalate. This means that there is less oxalate in the body to build up and make crystals which means there is less chance of stones and of the kidneys becoming damaged.

• If the kidneys are already very damaged then it may mean that the job of the kidneys needs to be done by a dialysis machine or that you need a transplant. In the past PH1 patients in this situation usually needed a liver and kidney transplant but with the new treatments it may be that you only need a kidney transplant.
• As the kidneys become more damaged, oxalate can also build up in different organs – usually bone, skin, the retina (part of the eye) and the heart muscle.

What is Secondary Hyperoxaluria

Secondary or enteric hyperoxaluria is when the urine and blood oxalate levels are high because someone is eating a lot of food which is rich in oxalate or if they have another condition or illness which affects the gut.

In enteric hyperoxaluria there are three main ways that the oxalate levels in the body become high:

1. Too much oxalate in your diet (click here for more information about food and oxalate). see dietary advice
2. In some illnesses fat is not absorbed properly in the gut, this means your gut finds it easier to absorb oxalate so more oxalate stays in the body. In these conditions you often have stools which are pale and oily.
   Some of the conditions that can cause fat malabsorption are pancreatic disorders, Roux-en-Y bypass (gastric bypass) surgery, short bowel disease, Crohn´s disease, or if you take a drug called Orlistat. Click here for a full list of conditions which can affect oxalate in the gut.
3. The oxalate in your gut doesn´t get broken down as easily because of changes to the „friendly“ bacteria which live in your gut. This can sometimes happen if you have had multiple courses of antibiotics or gastrointestinal infections.
   
   The cause can also be a combination of these things.

Secondary Hyperoxaluria: What can be done?

• Everyone is different and it is always important to talk to your own doctor
• Most patients will be advised to drink lots of water (>3L/day)
• Eating a low oxalate diet can help (see our diet page)
• Other dietary changes such as low fat and normal/high calcium diets can be helpful
• Mostly treatments will be guided towards treating the underlying illness (affecting the gut)
• Medications to bind oxalate in the gut or reduce the amount of oxalate in the urine can be tried
• If the kidney damage is severe, treatment to take over the job of the kidneys such as dialysis or a transplant might be needed