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If you would like to discuss your kidney diagnosis with our trained members of staff, ring our free-to-call number. The NKF Helpline is available Monday to Thursday 08:30 am - 5:00 pm Friday 8.30 am – 12.30 pm on 0800 169 09 36 or email [email protected]

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Alnylam Pharmaceuticals funded the National Kidney Federation to develop this content.

Job number: PH1-UK-00045 | Date of preparation: January 2025

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What is PH1?

Primary hyperoxaluria (PH) is a group of rare genetic diseases with three types: type 1 (PH1), type 2 (PH2) and type 3 (PH3). It is estimated that between 1 and 3 in every million people in Europe have PH1 (or about 200 people in the UK). However as with many rare diseases, it is likely many people remain undiagnosed or with an incorrect diagnosis.

Approximately three quarters of people with PH are diagnosed as type 1. PH type 1 (PH1) is a rare genetic condition that is caused by a problem in the liver and usually affects the kidneys. 

Causes of PH1

PH1 is a genetic condition. A genetic condition, also referred to as an inherited disease, occurs when genes that are not working correctly are passed from a parent to a child. There are over 60 known inherited kidney diseases, which range from common conditions to very rare diseases. 

PH1 is caused by a fault in a gene called AGXT which makes an enzyme in your liver called alanine-glyoxylate aminotransferase (AGT) not work properly. When AGT works properly it helps process waste products in your body. When the gene has fault, such as in people living with PH1, there is an unusual buildup of a substance called oxalate, typically found in various foods and also naturally in our bodies.

Your kidneys usually filter oxalate out of the blood and into the urine. However, people living with PH1 have build ups of oxalate in their body and high levels of oxalate in their urine. This increases the risk of calcium oxalate stones (a type of kidney stone) in the kidney and/or bladder.  The build-up happens in the kidneys at first and can cause kidney damage or even failure, but it also builds up in other organs causing harm to other parts of the body.

Symptoms of PH1

The symptoms of PH1 can be varied, and PH1 can affect members of a family in different ways.

The signs of PH1 may not always be noticeable; they can go unrecognised or be confused with the signs of other disorders. Adults with PH1 can wait several years or longer after experiencing their first symptom before they receive a PH1 diagnosis.

Symptoms of PH1 include:

• kidney stones
• not growing sufficiently as a baby
• Deterioration in kidney function
• kidney failure
• nephrocalcinosis (finding crystals in kidney tissue during a kidney scan).

The earliest and most common sign of PH1 is often kidney stones.

In children and teenagers,  one episode of kidney stones alone should raise the level of suspicion for PH1. In adults, having multiple kidney stone episodes may indicate PH1. Not all people with PH1 will have kidney stones, though your kidneys are still at risk for damage even if you are not passing kidney stones.  

Symptoms of kidney stones include:

• pain in the lower back on one or both sides
• painful urination
• blood in the urine
• fever
• urinary tract infections (UTIs)

People of South Asian origin may be at higher risk of genetic kidney diseases for more information about this, please watch the following video or download the leaflet below on genetic kidney disease in South Asian communities.

Diagnosis

Around 50% of people living with PH1 may be undiagnosed, although data on how many people have PH1 is limited.

Because of PH1’s ultra-rare nature, it can be mistaken for other conditions. Therefore, early diagnosis is crucial to catch the disease before it causes widespread damage and to allow for appropriate management of symptoms.

If your doctor suspects you might have PH1, you may undergo one or more of the following tests :

• Metabolic testing
• 24 hour or spot urine collection
• Blood plasma oxalate test
• Genetic testing for damaged AGXT gene

Disease management

The goal of management is to slow disease progression. Current management options help decrease the amount of crystals formed due to oxalate overproduction, to slow down kidney damage and lower stone formation.

If you have PH1, your management may change over time, depending on how your disease and symptoms progress. It is important to monitor the condition closely with your doctor and healthcare team.

There are a number of ways to manage the condition, your doctor may consider options such as:

• Hyperhydration (drinking lots of water): Helps dilute oxalate in your urine
• Alkali citrate (potassium citrate or sodium citrate): May help reduce crystal formation
• Pyridoxine (vitamin B6): May help the broken enzyme in your liver try to work normally.
• RNA interference (RNAi): This treatment “silences” or turns off the production of specific genes involved in oxalate production.
• Emerging therapies: Potential therapies currently being researched target and prevent oxalate development in the liver. Your doctor may consider these experimental treatments or clinical trials where available.

If PH1 has affected your kidneys' ability to work properly, you may need to undergo dialysis and/or a transplant. Dialysis is a process that uses a machine to help remove waste products (such as oxalate) and excess fluid from the blood when your kidneys are no longer able to work properly. For transplantation, a combined liver and kidney transplant may be recommended to fix the way your body is handling oxalate.

What should I do next?

If you think you have a history of kidney problems in your family, discuss this with your GP first. They might refer you onto a specialist, who will know more about kidney health and treatment and give you the right course of action.

Knowing you have a kidney disease as early as possible can help you take steps to manage the condition and help improve your outcomes.  A diagnosis can help you and your family members.

For more information on kidney disease, visit our ‘What is kidney disease’ page, or our ‘Rare Renal Conditions’ page.

Download our PDF on genetic kidney disease in South Asian communities

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The National Kidney Federation cannot accept responsibility for information provided. The above is for guidance only. Patients are advised to seek further information from their own doctor.