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Primary hyperoxaluria: a plain-language guide

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Keith

Primary hyperoxaluria is a rare inherited condition in which the liver makes far too much of a waste substance called oxalate, which the kidneys then have to remove, causing kidney stones, kidney damage and, once kidney function falls, deposits of oxalate throughout the body [1,5].

This page provides general information. It does not replace advice from a doctor or another qualified healthcare professional.

Key facts

  • There are three types, each caused by a change in a different gene: type 1 from the AGXT gene, which is the most common and usually the most severe, type 2 from GRHPR and type 3 from HOGA1 [1].
  • All three types are inherited in an autosomal recessive pattern, which means a child has to inherit a changed copy of the same gene from both parents [1].
  • Type 1 often shows itself in childhood. Around 7 in 10 people with type 1 have their first symptoms between the ages of 1 and 17, and about 1 in 10 in the first year of life [2].
  • Kidney stones and nephrocalcinosis, which means tiny oxalate deposits spread through the kidney tissue, are the usual first signs [1,2].
  • Once kidney function drops below about 30 percent of normal, oxalate builds up in the blood and settles in bones, eyes, heart, blood vessels and other tissues. This is called systemic oxalosis, and it is the main reason early diagnosis is so important [2,5].
  • Two medicines that lower oxalate production, lumasiran and nedosiran, are approved for type 1. Nothing is yet approved for types 2 or 3 [9,10,4].

On this page

What is primary hyperoxaluria?

Oxalate is a natural waste substance the body cannot use, and normally the liver makes only a little. In primary hyperoxaluria the liver makes far too much, and the kidneys have to remove it all [1].

In the urine, oxalate joins with calcium to form calcium oxalate, which barely dissolves. It builds up as kidney stones, and as tiny deposits spread through the kidney tissue itself, called nephrocalcinosis [1,2].

Each type comes from a change in a different gene. Type 1, from the AGXT gene, causes roughly 80 percent of cases and is usually the most severe. Type 2 comes from GRHPR and type 3 from HOGA1, each about 10 percent [1]. The condition is also called oxalosis [1].

Secondary and enteric hyperoxaluria are different problems, often confused with this one. There the liver is normal and the gut absorbs too much oxalate from food [18]. Most people with high urine oxalate have that kind [23].

How common is it?

Primary hyperoxaluria is rare, and nobody knows exactly how rare.

Counts of people actually diagnosed suggest 1 to 3 per million [24], and the United Kingdom figure is about 1 in 500,000 [12]. Estimates based on genes are much higher: a 2025 study put the chance of being born with a form of the condition at about 1 in 59,000 [7]. Such numbers count people carrying two changed copies of a gene, not people with symptoms.

The reasons for the gap are clear. Kidney stones are common, so the condition gets missed. Some people with changed genes never develop problems, especially in type 3. Some babies with the severest form die before anyone works out why [7]. Males and females are equally affected [14].

Rates differ by ancestry: carrier rates for HOGA1 are highest in people of Ashkenazi Jewish ancestry [7]. Disease starting in the first year of life is far more common where marriage between relatives is usual [2].

What causes it?

Genes are the instructions cells use to make proteins. Enzymes are proteins that carry out chemical steps. Here a gene change leaves an enzyme missing or weak, so a substance called glyoxylate is not broken down and turns into oxalate instead [1]. Type 1 affects an enzyme found only in the liver, which is why the liver is the source of the extra oxalate. Type 2 affects another enzyme in the same pathway, and in type 3 the reason oxalate rises is still not fully understood [1,4].

All three types are inherited in an autosomal recessive pattern. Everyone has two copies of each gene, one from each parent. Someone with one changed copy is a carrier and is almost always healthy, because the working copy does the job [1,12]. A child is affected only when both copies are changed, so when both parents are carriers each pregnancy has a 1 in 4 chance. Genetic counseling and testing for siblings are usually offered [4,12].

Nothing a parent did causes this, and severity varies widely even between siblings with the same gene changes [2].

What are the symptoms?

Symptoms come mostly from stones. In type 1, about 1 in 10 people are affected in the first year of life, when the usual findings are nephrocalcinosis on a scan, poor growth, and kidney function already badly reduced. Around 7 in 10 have their first symptoms between ages 1 and 17, most often before age 10, and around 2 in 10 are first diagnosed as adults [2].

Common signs at any age include [2,22]:

  • sharp pain in the back, side, lower abdomen or groin, coming and going in waves
  • blood in the urine, sometimes visible, sometimes found only on a test
  • urinary infections, and in children frequent bedwetting

Type 2 is usually milder, and type 3 often causes stones earliest, before age 3, yet rarely leads to kidney failure [4].

Once kidney function falls below about a third of normal, oxalate builds up in the blood and settles in other tissues. This is systemic oxalosis, and it can affect bones, the retina, the heart, blood vessels and nerves [2,5]. It has not been reported in type 3 [4].

When to seek urgent help. Contact the kidney team, or emergency care if the team is not quickly reachable, if there is [6,21]:

  • much less urine than usual, or none
  • severe pain in the back or side, especially with vomiting
  • fever or shivering with stone pain, which can mean an infected blockage
  • vomiting or diarrhea that stops normal drinking, since even mild dehydration harms the kidneys
  • feeling unwell in the days after a stone procedure

Children often need fluids through a drip during such illnesses. Most people never face a sudden emergency, and a written plan agreed with the team in advance helps [6].

How is it diagnosed?

Care is usually shared between a kidney specialist, or nephrologist, a stone surgeon and a genetics service [4].

A first kidney stone in a young child should prompt investigation rather than watchful waiting. Stones are unusual at that age, a cause is often found, and children who form stones carry higher long-term kidney risk [19]. Primary hyperoxaluria should also be considered in anyone with repeated calcium stones, nephrocalcinosis, or unexplained loss of kidney function [2].

Testing starts with the amount of oxalate in the urine, collected over 24 hours, or measured against creatinine on a single sample in babies. Two collections are used, since one can mislead. Once kidney function is well down, a blood oxalate level is more useful. A passed stone can be analyzed, and an ultrasound scan looks for stones and nephrocalcinosis [2,12]. Genetic testing of the three genes then confirms the diagnosis and the type [2,5]. Secondary and enteric causes are ruled out first, since oxalate levels can overlap [5].

Diagnosis is often late, and many adults are identified only once kidney function is low [2].

How is it treated?

There is no cure, apart from a liver transplant in type 1, which replaces the missing enzyme [5]. Treatment aims to make less oxalate, keep it dissolved in the urine, and protect the kidneys.

Fluid and citrate. Fluid is the foundation: around 3.5 to 4 liters a day for adults, and an amount scaled to body size in children, spread over 24 hours. Babies often cannot manage this by mouth, so a feeding tube is sometimes used, including overnight [5,19]. Potassium citrate is also taken daily, to stop calcium oxalate crystals forming [5,6].

Diet. A strict low-oxalate diet is not recommended, since the oxalate is made in the liver and food adds little. Guidelines suggest a normal balanced diet that avoids only extremely high-oxalate foods, with normal calcium intake [5,6].

Vitamin B6. Pyridoxine, or vitamin B6, helps only in type 1 and only in some people, since it props up the faulty enzyme and so depends on which AGXT variant a person has. Between 30 and 50 percent of people with type 1 respond [2], and there is no supporting evidence for it in type 2 [3].

RNA interference medicines. These injections under the skin turn down a liver enzyme so less oxalate is made. Both are approved for type 1 only, not for type 2 or type 3 [2,4]. Lumasiran has been approved since late 2020 by the United States Food and Drug Administration and the European Medicines Agency, for type 1 at any age [2,9], and NICE recommends it in England [11]. Nedosiran is approved only in the United States, for children aged 2 and over and adults with type 1 and relatively preserved kidney function [10,8].

Stones and dialysis. Blockages need relieving promptly. Where a stone must be removed, ureteroscopy or a percutaneous approach is preferred over shock wave lithotripsy, since these stones resist sound waves and shock waves risk kidney injury [5,21]. Ordinary dialysis cannot keep pace with the oxalate produced, so hemodialysis six or seven times a week is often needed [12].

Transplantation. In type 1 a kidney on its own is usually not enough, since the liver carries on overproducing oxalate and damages the new kidney in turn. Combined liver and kidney transplantation gives much better long-term kidney survival, together or one after the other. A kidney alone can be considered where the disease responds well to vitamin B6 [5]. In type 2 the approach is decided case by case, and in type 3 kidney failure is rare [3,6].

Availability differs sharply: one survey found lumasiran available in about half of 57 countries, mostly high-income, and in no low-income ones [8].

Living with primary hyperoxaluria

Most people are followed long term by a specialist center and are never discharged [5].

Daily life is shaped by fluid, spread through the day and often the night, which affects sleep, school and work. Children do better with a school plan so they can carry water and use the bathroom freely. An illness plan helps too, since vomiting or diarrhea can quickly become a kidney problem [6].

Monitoring is routine rather than dramatic: urine and blood oxalate, kidney function, and a scan at least yearly, with eye and heart checks when kidney function is low [5,6]. Carrying a note of the diagnosis is sensible, since it changes decisions around surgery and about medicines affecting the kidneys.

Siblings are usually offered testing, and carrier testing can be offered to partners [4]. Published information on pregnancy is very limited: one report of four pregnancies in women with type 1 found all four babies born healthy at term [20].

For parents of a baby diagnosed in the first months, patient organizations are often the fastest route to people who have lived it [25].

Thinking about a clinical trial?

Clinical trials test whether a treatment works and is safe. Primary hyperoxaluria is rare, so studies are fewer and many run at a few specialist centers. Deciding whether to look into one is personal, and it helps to take it in steps.

1. Understand what the study is asking

It is worth being clear on what a study involves:

  • what the researchers are trying to learn
  • what is being studied, and what it is compared with
  • how long the study lasts, since kidney studies often run a year or more
  • what visits and tests are involved and how often, including timed urine collections
  • the possible benefits, and the known and unknown risks
  • what happens when the study ends, including whether treatment continues

2. Consider possible medical suitability

Every trial has rules about who can take part, called eligibility criteria. Some describe who can join, others who cannot. For a primary hyperoxaluria study they might include a diagnosis confirmed by genetic testing, a specific type, a set amount of oxalate in the urine, kidney function within a set range, a minimum age or weight, and not already taking another medicine that lowers oxalate.

trialport’s medifit helps people consider information related to possible medical suitability. It does not diagnose a condition, confirm eligibility or replace formal screening by the study team.

Explore primary hyperoxaluria clinical trials through trialport

3. Consider whether participation fits your life

Medical suitability is only part of the picture. A study can look right on paper and still be hard in practice. Worth thinking through:

  • how much time each visit takes, and how many there are
  • travel and distance, since specialist centers are often far away, and who would come along
  • work, school or caring responsibilities, and how much time off is realistic
  • for a parent deciding for a young child, how the child copes with needles, scans and hospital days
  • whether you understand the study well enough to decide, and whether it feels right now

trialport’s readifit helps people reflect on their understanding, motivation, time, routines, support, emotions and practical arrangements.

4. Ask questions before deciding

Useful questions to put to a research team:

  • Why is this study being carried out, and what is already known?
  • Which type of primary hyperoxaluria is this study for?
  • What exactly would we need to do, and for how long?
  • What are the known risks, and what is still unknown?
  • Could I receive a placebo? A placebo is a dummy treatment with no active medicine, used so researchers can compare results fairly. Would usual treatment continue alongside it?
  • Can we leave the study after joining, and what happens if we do?
  • Who provides usual kidney care during the study, and who do we contact out of hours?
  • Could the treatment continue after the study ends?

Taking part is voluntary. A person can ask questions, speak with people they trust and choose not to participate.

Search for clinical trials at app.trialport.com.

Current research

  • Longer-term results for the approved medicines. Researchers are following people treated with lumasiran and nedosiran to see whether lower oxalate means fewer stones and steadier kidney function over years [2].
  • Types 2 and 3. No medicine is approved for either. Work on blocking a liver enzyme called LDH is relevant to all three types, and studies in type 3 have been under way [4].
  • Small molecules and gene editing. An epilepsy medicine, stiripentol, blocks the same enzyme and has been looked at in small reports, and gene editing aimed at the liver is at an earlier stage [4,21]. Neither is an approved treatment.

Study status checked: 3 August 2026. Research moves and what is studied changes, so this list will date. For current information, search at app.trialport.com.

Support and further information

In the United States, the Oxalosis and Hyperoxaluria Foundation is the main condition-specific organization, covering all forms of hyperoxaluria, with plain-language education, specialist care centers and a patient community [15].

In Europe, PH Europe is an independent patient network with country contacts and family-focused material [25]. OxalEurope is a group of clinicians and scientists rather than a patient organization, useful for finding expert centers [16]. ERKNet, the European Reference Network for rare kidney diseases, publishes the main clinical guideline with a plain-language summary for families [17].

In the United Kingdom, Kidney Care UK has quality-marked information and a free support line [12], and the UK Kidney Association lists the specialist adult and children’s centers in its hyperoxaluria network [13].

Coverage elsewhere is thin, and no condition-specific organization could be verified for Australia and New Zealand, Asia, the Middle East, Africa or South America. Elsewhere, a national kidney association or the treating kidney unit is the best start [15].

Questions people often ask

How is this different from ordinary kidney stones?
Most stones form for common reasons in people with healthy kidneys. Here the liver makes far too much oxalate constantly, so stones keep returning and the kidney is damaged [1,23].

My child has had one kidney stone. Should they be tested?
Yes. A first stone in a young child should be investigated rather than watched, since stones are unusual then and a cause is often found [19].

Will cutting out spinach and chocolate fix it?
No. A strict low-oxalate diet is not recommended, since the oxalate is made in the liver rather than coming from food [5,6].

Does vitamin B6 work for everyone?
No. It helps only in type 1, and only in people with certain gene variants, so between 30 and 50 percent respond [2]. There is no evidence supporting it in type 2 [3].

Why might a kidney transplant on its own not be enough?
In type 1 the problem sits in the liver, so a new kidney does not stop oxalate being made. A combined liver and kidney transplant is usually recommended, and replacing the liver is the only cure [5].

Are the parents ill too?
Almost never. Parents are usually carriers, with one changed copy of the gene and one working copy, and carriers are typically healthy [12].

Sources

  1. MedlinePlus Genetics (US National Library of Medicine). Primary hyperoxaluria. Last updated 1 December 2015. https://medlineplus.gov/genetics/condition/primary-hyperoxaluria/ Accessed 3 August 2026.
  2. Milliner DS, Harris PC, Sas DJ, Cogal AG, Lieske JC. Primary Hyperoxaluria Type 1. In: GeneReviews. Seattle: University of Washington. Initial posting 19 June 2002, updated 11 December 2025. https://www.ncbi.nlm.nih.gov/books/NBK1283/ Accessed 3 August 2026.
  3. Rumsby G, Hulton SA. Primary Hyperoxaluria Type 2. In: GeneReviews. Seattle: University of Washington. Initial posting 2 December 2008, updated 21 December 2017. https://www.ncbi.nlm.nih.gov/books/NBK2692/ Accessed 3 August 2026.
  4. Milliner DS, Harris PC, Sas DJ, Lieske JC. Primary Hyperoxaluria Type 3. In: GeneReviews. Seattle: University of Washington. Initial posting 24 September 2015, updated 9 February 2023. https://www.ncbi.nlm.nih.gov/books/NBK316514/ Accessed 3 August 2026.
  5. Groothoff JW, Metry E, Deesker L, et al. Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope. Nature Reviews Nephrology. 2023;19(3):194-211. doi:10.1038/s41581-022-00661-1. https://www.erknet.org/fileadmin/files/pdf/Clinical_practice_recommendations_for_primary_hyperoxaluria_an_expert_consensus_statement_from_ERKNet_and_OxalEurope.pdf Accessed 3 August 2026.
  6. Michael M, Harvey E, Milliner DS, et al. Diagnosis and management of primary hyperoxalurias: best practices. Pediatric Nephrology. 2024;39:3143-3155. doi:10.1007/s00467-024-06328-2. https://doi.org/10.1007/s00467-024-06328-2 Accessed 3 August 2026.
  7. Mandrile G, Rumsby G, Sciannameo V, Cogal AG, Glover M, Lieske JC, Harris PC. Global genetic prevalence estimates of primary hyperoxaluria are greater than previously reported. Clinical Kidney Journal. 2025;18(7):sfaf194. doi:10.1093/ckj/sfaf194. https://academic.oup.com/ckj/article/18/7/sfaf194/8168204 Accessed 3 August 2026.
  8. Deesker LJ, et al. Global access to management of primary hyperoxaluria: a survey on behalf of OxalEurope, G&K Working Group of the ERA and ESPN. Nephrology Dialysis Transplantation. 2025;40(9):1688-1697. doi:10.1093/ndt/gfaf035. https://academic.oup.com/ndt/article/40/9/1688/8029907 Accessed 3 August 2026.
  9. European Medicines Agency. Oxlumo (lumasiran): overview. Marketing authorization issued 19 November 2020, page last updated 13 October 2025. https://www.ema.europa.eu/en/medicines/human/EPAR/oxlumo Accessed 3 August 2026.
  10. DailyMed (US National Library of Medicine). RIVFLOZA (nedosiran) injection, solution: prescribing information. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ace9d4bc-4d20-4beb-9e9d-888690424833 Accessed 3 August 2026.
  11. National Institute for Health and Care Excellence. Lumasiran for treating primary hyperoxaluria type 1. Highly specialised technologies guidance HST25, published 19 April 2023. https://www.nice.org.uk/guidance/hst25 Accessed 3 August 2026.
  12. Kidney Care UK. Hyperoxaluria. Publication date November 2023, review date November 2026. https://kidneycareuk.org/kidney-disease-information/kidney-conditions/hyperoxaluria/ Accessed 3 August 2026.
  13. UK Kidney Association. Hyperoxaluria: Rare Disease Group and Rare Disease Collaborative Network. https://www.ukkidney.org/rare-renal/rare-disease-groups/hyperoxaluria Accessed 3 August 2026.
  14. National Organization for Rare Disorders. Primary Hyperoxaluria. Last updated 23 January 2024. https://rarediseases.org/rare-diseases/primary-hyperoxaluria/ Accessed 3 August 2026.
  15. Oxalosis and Hyperoxaluria Foundation. https://ohf.org/ Accessed 3 August 2026.
  16. OxalEurope, European Consortium of Hyperoxaluria. https://oxal-europe.org/ Accessed 3 August 2026.
  17. European Reference Network for Rare Kidney Diseases (ERKNet). Hyperoxaluria: guidelines and pathways. https://www.erknet.org/guidelines-pathways/metabolic-stone-disorders/hyperoxaluria Accessed 3 August 2026.
  18. Cellini B, Baum MA, Frishberg Y, Groothoff JW, Sas DJ, et al. Opportunities in Primary and Enteric Hyperoxaluria at the Cross-Roads Between the Clinic and Laboratory. Kidney International Reports. 2024;9(11):3083-3096. https://pmc.ncbi.nlm.nih.gov/articles/PMC11551133/ Accessed 3 August 2026.
  19. Injeyan M, Bidault V, Bacchetta J, Bertholet-Thomas A. Hydration and Nephrolithiasis in Pediatric Populations. Nutrients. 2023;15(3):728. https://pmc.ncbi.nlm.nih.gov/articles/PMC9920266/ Accessed 3 August 2026.
  20. Miao J, Mehta RA, Kattah A, Norby SM, Lieske JC, Milliner DS. Urinary Oxalate Excretion During Pregnancy in Primary Hyperoxaluria Type 1: A Report of 4 Cases. Kidney Medicine. 2024;6(6):100824. https://pmc.ncbi.nlm.nih.gov/articles/PMC11141431/ Accessed 3 August 2026.
  21. Martinez-Galindo R, Campuzano-Perez M, Konstantouli A, et al. Clinical Approaches and Emerging Therapeutic Horizons in Primary Hyperoxaluria. Journal of Clinical Medicine. 2026;15(3):940. https://www.mdpi.com/2077-0383/15/3/940 Accessed 3 August 2026.
  22. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney Stones in Children. Last reviewed May 2017. https://www.niddk.nih.gov/health-information/urologic-diseases/kidney-stones-children Accessed 3 August 2026.
  23. Shah A, Leslie SW, Ramakrishnan S. Hyperoxaluria. In: StatPearls. Treasure Island: StatPearls Publishing. Last updated 4 March 2024. https://www.ncbi.nlm.nih.gov/books/NBK558987/ Accessed 3 August 2026.
  24. Orphanet. Primary hyperoxaluria (ORPHA:416). Last update January 2020, expert reviewers J.W. Groothoff and B. Hoppe. https://www.orpha.net/en/disease/detail/416 Accessed 3 August 2026.
  25. PH Europe, Primary Hyperoxaluria Support Network. https://www.ph-europe.net/ Accessed 3 August 2026.

Review information

Written by: trialport editorial team
Reviewed by: Keith Berelowitz, Founder and CEO, trialport
Reviewed on: 3 August 2026
Next review due: 3 August 2027
References last checked: 3 August 2026