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Health condition

Hyperoxaluria, from recurrent stones to modern siRNA therapy.

A rare but treatable metabolic disease. Early diagnosis, hydration, dietary strategy and drugs like lumasiran are changing what this diagnosis means.

Jump to treatment
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Why trust this guide

  • 01

    Editorial team

    Written by our editorial team from the UK sources listed on each page.

  • 02

    Sourced from guidance

    Checked against KDIGO, international primary hyperoxaluria consensus and NICE technology appraisals.

  • 03

    Current for 2026

    Reflects modern practice including lumasiran (Oxlumo) and nedosiran (Rivfloza) siRNA therapy.

Key facts

Hyperoxaluria at a glance.

The essentials, in plain English - what it is, the types, and how it is diagnosed and managed today.

  • What it is

    Elevated urinary oxalate excretion driving recurrent calcium oxalate kidney stones, nephrocalcinosis and, in severe cases, systemic oxalosis.

  • Primary types

    Autosomal recessive PH1 (AGXT), PH2 (GRHPR) and PH3 (HOGA1). PH1 is the commonest and most severe.

  • Secondary causes

    Enteric hyperoxaluria from short bowel, IBD, bariatric surgery, chronic pancreatitis or cystic fibrosis, plus dietary excess.

  • Complications

    Recurrent nephrolithiasis, nephrocalcinosis, progressive CKD to end-stage renal disease and multi-organ systemic oxalosis.

  • Modern therapy

    Lumasiran and nedosiran (RNA interference) have transformed PH1 care and reduced the need for transplantation.

  • Where it is managed

    Specialist nephrology commissioned services, with MDT input from hepatology, gastroenterology and genetics.

Why this guide matters

A rare disease, transformed.

Once a childhood diagnosis that led to combined liver-kidney transplant, primary hyperoxaluria now has effective medical therapy. The three points below shape everything else on this page.

  • Diagnosis has moved to genetics

    Genetic testing for AGXT, GRHPR and HOGA1 has replaced liver biopsy as the confirmatory investigation - available through specialist commissioned services.

  • siRNA has changed outcomes

    Lumasiran and nedosiran silence the genes that drive oxalate overproduction - shifting the disease from irreversible to controllable.

  • Secondary causes matter

    Enteric hyperoxaluria in short bowel, IBD or after bariatric surgery is common and treatable - screening for it is worth the effort.

How the diagnosis is made

From first stone to a metabolic answer.

The path a UK nephrologist normally follows, in order - so you know what to expect and why.

  1. 01

    Assessing

    History and family screen

    Age at first stone, family history of stones or ESRD, bowel disease, bariatric surgery and diet - all point towards primary or secondary hyperoxaluria.

  2. 02

    Assessing

    Stone analysis

    Every retrieved stone should be analysed - calcium oxalate monohydrate (whewellite) predominance is a red flag for hyperoxaluria.

  3. 03

    Assessing

    24-hour urine collection

    Urinary oxalate, citrate, calcium, uric acid, magnesium and creatinine - the cornerstone of metabolic stone assessment.

  4. 04

    Confirming

    Plasma oxalate and glycolate

    Elevated plasma oxalate suggests advanced disease or ESRD. Glycolate and glycerate levels help distinguish PH1, PH2 and PH3.

  5. 05

    Confirming

    Genetic testing

    AGXT, GRHPR and HOGA1 sequencing is now first-line for suspected primary hyperoxaluria - specialist commissioned service.

  6. 06

    Confirming

    Imaging - ultrasound and CT

    Renal ultrasound and low-dose CT identify stones, nephrocalcinosis and hydronephrosis. See our private CT scan page for context.

  7. 07

    Preparing

    MDT specialist review

    Nephrology, hepatology, gastroenterology and genetics coordinate care. Liver biopsy is now rarely needed given modern genetics.

Typical timeline: from suspicion to genetic confirmation in weeks with specialist input.

Symptoms

What hyperoxaluria actually looks like.

Recurrent stones, silent nephrocalcinosis and, when advanced, multi-organ oxalosis. And the features that mean urgent specialist referral.

  • Recurrent kidney stones

    Repeated calcium oxalate stones - often from childhood or young adulthood - are the classic presentation.

  • Renal colic and flank pain

    Severe loin-to-groin pain during stone passage - often the first clue to underlying metabolic disease.

  • Haematuria

    Visible or microscopic blood in the urine, often with a passing stone or urinary tract infection.

  • Nephrocalcinosis

    Diffuse calcium oxalate deposition within the renal parenchyma - visible on ultrasound and CT.

  • Progressive CKD

    Falling eGFR, proteinuria and rising creatinine - see our patient guide on kidney failure.

  • Failure to thrive in infants

    Severe PH1 can present in infancy with poor feeding, growth failure and rapidly progressive renal disease.

  • Systemic oxalosis

    When plasma oxalate is very high, crystals deposit in bone, heart, retina, skin and vessels - a late-stage feature.

  • Red flag - childhood ESRD

    Any child or young adult reaching end-stage renal disease from unexplained stones deserves urgent genetic testing.

Treatment

How hyperoxaluria is treated today.

Hydration and diet first, then metabolic therapy - and, for primary disease, gene-silencing drugs that have transformed the outlook.

  • High fluid intake

    More than 3 litres per day in adults - the single most important intervention. Dilutes urinary oxalate and reduces stone risk.

  • Dietary modification

    Reduce high-oxalate foods (spinach, rhubarb, chocolate, nuts, tea). Maintain normal dietary calcium - it binds oxalate in the gut.

  • Potassium citrate

    Alkalinises urine and increases citrate, an inhibitor of calcium oxalate crystallisation. Titrated by a specialist.

  • Pyridoxine (vitamin B6)

    Around 30 percent of PH1 patients - particularly those with specific AGXT mutations - respond to high-dose vitamin B6.

  • Lumasiran (Oxlumo)

    Monthly then quarterly subcutaneous siRNA that silences hepatic glycolate oxidase. NICE-approved for PH1. See our lumasiran page.

  • Nedosiran (Rivfloza)

    Once-monthly subcutaneous siRNA targeting hepatic LDHA. FDA-approved for PH1, PH2 and PH3 in appropriate patients.

  • Dialysis for ESRD

    Intensive haemodialysis is often needed to clear the high oxalate burden - specialist commissioned service.

  • Combined liver-kidney transplant

    Historically the definitive cure for PH1 by replacing the deficient hepatic enzyme. Still relevant where siRNA is unavailable or ineffective.

What this guide is based on

The sources behind every claim on this page.

International guidance, NICE technology appraisals and specialist society consensus, current at the time of last review.

Key references

Guidelines and standards we relied on.

A quiet reminder

This guide is for information, not medical advice.

Your nephrologist knows your case and can tell you which parts apply to you. If in doubt, get seen.

  • KDIGO. Clinical practice guideline on the evaluation and management of primary hyperoxaluria.

  • NICE TA710. Lumasiran for treating primary hyperoxaluria type 1.

  • Oxalosis and Hyperoxaluria Foundation (OHF). Patient information and clinician resources.

  • European Rare Kidney Disease Reference Network (ERKNet). Primary hyperoxaluria consensus.

  • British Association of Paediatric Nephrology. Guidance on paediatric stone disease.

Red flags

When hyperoxaluria needs urgent attention.

Some presentations demand rapid specialist review - the situations below should trigger a nephrology referral without delay.

  • Recurrent childhood stones

    Any child with more than one calcium oxalate stone should be worked up for primary hyperoxaluria without delay.

  • Rapidly progressive CKD

    Unexplained falling eGFR alongside nephrocalcinosis or stones is a strong signal for urgent specialist referral.

  • Systemic oxalosis

    Bone pain, cardiac conduction disease, retinal changes or livedo reticularis in a stone-former is a late-stage emergency.

  • ESRD in a young adult

    End-stage renal disease before 40 - especially with a history of stones - warrants genetic testing.

  • Post-bariatric hyperoxaluria

    New stones years after Roux-en-Y gastric bypass may signal enteric hyperoxaluria and CKD risk.

  • Short bowel and IBD

    Patients with short-bowel syndrome or active inflammatory bowel disease are high risk - screen with 24-hour urines.

  • Failing infant

    Neonatal or infantile PH1 is a paediatric nephrology emergency - dialysis and transplant planning start immediately.

  • Pregnancy considerations

    Pregnancy raises oxalate loading and stone risk - patients on siRNA or transplant lists need pre-pregnancy counselling.

  • Family screening gap

    First-degree relatives of PH patients should be offered genetic testing - unrecognised carriers can present late.

Living with it

A rare disease, with a clear plan.

Four things that make the biggest difference day to day - hydration, dietary balance, structured monitoring and access to modern therapy.

A quiet reminder

Consistency beats intensity, every time.

Small, steady habits - kept up for years - do more than a heroic week that does not last.

  1. 01 Hydration

    Drink more than you think

    Aim for pale, dilute urine throughout the day - carry water, sip regularly and increase in hot weather or exercise.

  2. 02 Diet

    Balance, not elimination

    Keep dietary calcium normal, moderate oxalate-rich foods, and avoid high-dose vitamin C supplements which convert to oxalate.

  3. 03 Monitoring

    Annual reviews matter

    24-hour urines, renal function, imaging and plasma oxalate on a set schedule catch deterioration early.

  4. 04 Treatment

    Modern options are changing outcomes

    Lumasiran and nedosiran have transformed the outlook for PH1 - a specialist opinion is worth pursuing.

Frequently asked

Everything we get asked about hyperoxaluria.

Quick answers on primary types, diagnosis, siRNA therapy and when transplant is still needed.

  • What is hyperoxaluria?

    Hyperoxaluria is an excess of oxalate in the urine, which drives the formation of calcium oxalate kidney stones, nephrocalcinosis and, in severe cases, systemic deposition of oxalate crystals in bone, heart, skin and eyes. It can be primary (a rare genetic disease of hepatic oxalate metabolism) or secondary to gut disease or diet.

  • What is the difference between PH1, PH2 and PH3?

    Primary hyperoxaluria type 1 (PH1) is caused by AGXT mutations affecting alanine-glyoxylate aminotransferase in the liver - the commonest and most severe form. PH2 involves GRHPR (glyoxylate reductase) and PH3 involves HOGA1 (4-hydroxy-2-oxoglutarate aldolase). All three lead to oxalate overproduction, but severity and treatment responses differ.

  • How is hyperoxaluria diagnosed?

    Assessment begins with a careful history, stone analysis and a 24-hour urine collection measuring oxalate, citrate, calcium and creatinine. Plasma oxalate and glycolate levels help distinguish primary from secondary disease, and genetic testing (AGXT, GRHPR and HOGA1) now confirms the diagnosis in almost all suspected primary cases without the need for liver biopsy.

  • What is lumasiran and how does it work?

    Lumasiran (Oxlumo) is a small interfering RNA therapy given as a subcutaneous injection - initially monthly then quarterly. It silences hepatic glycolate oxidase (HAO1), reducing the upstream substrate for oxalate production. It is NICE-approved for PH1 and has revolutionised outcomes, often removing the need for combined liver-kidney transplantation.

  • Can diet cause hyperoxaluria on its own?

    Very high dietary oxalate combined with low calcium intake, dehydration, high-dose vitamin C or gut disorders that increase oxalate absorption can produce clinically significant hyperoxaluria - especially in patients with short-bowel syndrome, inflammatory bowel disease, bariatric surgery, chronic pancreatitis or cystic fibrosis. Pure dietary hyperoxaluria in an otherwise healthy adult is uncommon.

  • When is a transplant needed?

    Historically, combined liver-kidney transplantation was the definitive treatment for PH1 - the liver replaces the deficient enzyme and the kidney restores function. With lumasiran and nedosiran, many patients now avoid transplant. Transplantation still has a role where siRNA is unavailable, ineffective, or in advanced disease with systemic oxalosis.

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