Primary Hyperoxaluria Type 1

What is PH1?

Primary hyperoxaluria type 1 (PH1) is a rare and serious disease that mainly affects the kidneys. Primary refers to being born with the disease. Hyper means above normal, and oxaluria refers to oxalate in the urine.

PH1 is one of three hyperoxalurias, and type 1 is the most common. Each type is caused by a different gene. PH1 is caused by mutations (changes) in the alanine glyoxylate aminotransferase (AGXT) gene, which leads to excess oxalate in the body.

Oxalate is a substance normally filtered by the kidneys and removed in the urine. But in PH1, oxalate builds up in the kidneys and urinary tract. The excess oxalate then binds with calcium to form calcium oxalate stones. Too much calcium oxalate can also harm other parts of the body.

Early diagnosis is very important so that treatment can be started as soon as possible. This helps to maintain kidney function and overall good health. Without treatment, PH1 can lead to kidney failure, which means the kidneys stop working and a transplant or dialysis is needed to stay alive.

Closely following the healthcare team’s treatment plan, including their advice on currently available drugs and clinical trials, can lead to better outcomes.

What are the symptoms of PH1?

The symptoms of PH1 vary from mild to severe and can begin at any time between infancy and early adulthood. Symptoms are different for each person and may include frequent kidney stones, blood in the urine, and urinary tract infections.

People with very early-onset PH1, called infantile oxalosis, have severe symptoms before six months of age. People with milder forms of PH1 have no symptoms for over 40 or 50 years. The median age that symptoms appear is about 5-6 years.

Infants can have failure to thrive, which means they aren’t growing and developing at a normal rate, and they are weak.

How is PH1 diagnosed?

Finding a diagnosis for a genetic or rare disease is not easy. Healthcare professionals review a person’s medical and family history, symptoms, and they do a physical exam, along with blood and urine tests to make a diagnosis. However, the PH1 diagnosis is confirmed by genetic testing for the AGXT gene mutation. If no mutation is found through genetic testing, then a liver biopsy may be done by using a needle to pull out a tiny piece of the liver. Liver cells have the enzyme needed to prevent the build up of oxalate, so if no enzyme is found, or not enough of it, then this can help make the diagnosis.

How is PH1 treated?

The goal of treatment for PH1 is to decrease calcium oxalate build up and to maintain kidney function.

These recommendations for preventing calcium oxalate kidney stones help people with PH1, but first check with your healthcare team:

• drink a lot of fluid, mainly water
• use oral potassium citrate to prevent calcium oxalate crystals from forming
• use drugs such as thiazides to decrease calcium in the urine
• avoid large amounts of vitamin C or D since they can promote kidney stones
• eat and drink plenty of calcium

Decreasing oxalate production in the body includes treatment with the vitamin pyridoxine (vitamin B6). While not all people with PH1 respond to pyridoxine, it is recommended that everyone receive a minimum 3-month trial after diagnosis.

Dialysis to remove oxalate may be used in some people, but it usually can’t keep up with how fast the body produces oxalate.

Organ transplant is another treatment option, but experts have not yet decided on the best transplant approach. Options include: a liver and kidney transplant at the same time; a liver transplant first and then a kidney transplant; only a kidney transplant, or only a liver transplant.

Lumasiran, made by Alnylam Pharmaceuticals, is approved by the Food and Drug Administration (FDA) for the treatment of PH1 to lower oxalate levels in children and adults.

Coping with PH1

Living with a disease such as primary hyperoxaluria type 1 (PH1) can be physically and emotionally challenging for you and/or a loved one. It is very common to feel sad, scared, frustrated, or angry about living with PH1 and it is not uncommon to find that your emotions and feelings can change throughout the course of your disease. It is important to realize that any illness or disease can affect your mental health.

Living with a chronic disorder like PH1, can create stress. Managing stress is important for your physical and emotional wellbeing. Stress is a part of life, but too much stress can contribute to poor health. For more information on managing stress, click here

Remember, your emotions and physical health are inter-connected. A healthy emotional life may help you to live longer and feel better. Set reasonable goals for yourself. Be flexible. Allow for mistakes. Try to keep a positive attitude and keep doing things you enjoy. Spend time with people who make you laugh. All these things can help you stay healthy.

Finding support

Having people to turn to for support can be a great help while living with kidney disease, such as PH1. Don't be afraid to tell others what you are feeling and to ask for help and support when needed. Even your closest family members cannot read your mind. It is important to tell them how you feel. This is important advice for both patients and caregivers. Different kinds of people can help provide and offer emotional support. Among those who can be a part of your support system include:

• Family and friends
• People also living with the same disease
• A spouse or significant other
• Mentors and co-workers
• Members of your healthcare team
• Social, religious and spiritual groups

You can ask a member of your healthcare team about getting help from a social worker. Nephrology social workers are trained in kidney disease counseling to help patients and their families cope with their disease and changes in the family, home, workplace and community. They can help identify sources of emotional support for patients who are in need. They also identify services within federal, state and community agencies to meet patients' needs and help patients and families access services when necessary.

You can contact organizations like the National Kidney Foundation to help navigate the challenges of kidney diseases such as PH1: 855.NKF.CARES (855.653.2273), or nkfcares@kidney.org) and Online communities are also available for people to share their experiences, ask questions and get answers.