About Primary Hyperoxaluria Type 1 (PH1)

AN OVERVIEW OF PRIMARY HYPEROXALURIA TYPE 1

Primary hyperoxaluria type 1 (PH1) is a rare, progressive, inherited metabolic stone disease that is potentially life-threatening, and often presents with kidney stones.^1–3

PH1 IS A RARE, PROGRESSIVE, INHERITED METABOLIC STONE DISEASE^1–3

Primary hyperoxaluria (PH) is a group of autosomal recessive metabolic stone diseases resulting from defects in different enzymes involved in glyoxylate metabolism that lead to an overproduction of oxalate in the liver.^2,3There are 3 types of PH: PH1, PH2, and PH3, each of which is caused by a defect in a different enzyme.³

PH1 often presents with kidney stones and is caused by autosomal recessive mutations in the AGXT gene, which impairs the function of the liver-specific enzyme alanine:glyoxylate aminotransferase (AGT).^1,3 Normally, AGT processes glyoxylate, which is generated by another liver enzyme, glycolate oxidase (GO).^2,3

EARLIER DIAGNOSIS OF PH1 MAY HELP MITIGATE KIDNEY DAMAGE^2–6

PH1 is the most common—and most severe—type of PH^1,3,7

70%–80% of PH cases are PH1. Even so, PH1 is a rare disease, affecting an estimated 1 to 3 cases per million population, an incidence rate of 1 case per 120,000 live births per year in Europe, with higher prevalence in the Middle East and North Africa region.^1,3,7

PH1 can result in irreparable kidney damage^1,3

One of the most devastating aspects of PH1 is that it causes a progressive decline in kidney function, culminating in end-stage kidney disease (ESKD).^1,3,6 Moreover, there is the potential risk of systemic oxalosis.^3,8

Early diagnosis and intervention are key to mitigating damage^2–6

Management approaches may lessen damage by reducing stone formation and kidney deposition of calcium oxalate crystals; this underscores the importance of early diagnosis and intervention.^3,7,8

PH1 IS PROGRESSIVE AND SYSTEMIC^2,9

See how PH1 can be life-threatening²

PH1 leads to progressive decline in kidney function.²

EXCESS OXALATE CAN DAMAGE THE KIDNEYS⁹

Liver oxalate overproduction may lead to inflammation and progressive kidney function decline following calcium oxalate crystal formation.^8,9 Continuous oxalate overproduction may lead to irreversible damage in the kidneys and other organs.^8,9

PH1 advances at variable rates, progressing to ESKD.² When the kidneys are unable to excrete oxalate effectively due to toxicity from calcium oxalate crystal deposition, systemic oxalosis—the widespread tissue deposition of calcium oxalate—can occur.⁹ Complications from systemic oxalosis can be fatal.²

In some instances, kidney function can decline after a single incident of dehydration due to acute illness or intense physical activity.^10–13 This can occur even in patients with previously stable disease.^9,11

WHAT CAUSES OXALATE OVERPRODUCTION IN PH1?

Inability of AGT to process glyoxylate made by GO²

PH1 is a genetic disease caused by mutations in the AGXT gene that renders the liver enzyme AGT dysfunctional.³

Normally, AGT processes glyoxylate, which is generated by another liver enzyme, GO.^2,3 In PH1, a defect in AGT means glyoxylate is instead converted to oxalate.² Oxalate cannot be metabolised and is typically excreted by the kidneys at normal levels.³ When overproduced as it is in PH1, oxalate can wreak progressive, irreversible damage.² Oxalate combines with calcium, creating calcium oxalate crystals.² These crystals attach to kidney tissues, where they can aggregate to form kidney stones or lead to nephrocalcinosis.^2,9 As calcium oxalate accumulates, kidney excretion is impaired, and crystals deposit throughout the body.⁹

Download an overview of PH1

Given the nature of this disease, PH1 can go undiagnosed for many years. Early symptoms in adults, such as kidney stones, are often attributed to other, much more common conditions. We need to help physicians recognise symptoms faster, to stop progression before a patient reaches end-stage renal failure.

Kim Hollander

Executive Director, Oxalosis and Hyperoxaluria Foundation

Testing patients for PH1

See how genetic testing plays an important role in a PH1 diagnosis.^2,4

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References: 1. Hoppe B. Nat Rev Nephrol. 2012;8(8):467–475. 2. Milliner DS, Harris PC, Sas DJ, et al. Primary hyperoxaluria type 1. GeneReviews^® [Internet]. Updated 15 August 2024. Accessed January 2025. https://www.ncbi.nlm.nih.gov/books/NBK1283/ 3. Cochat P, Rumsby G. N Engl J Med. 2013;369(7):649–658. 4. Cochat P, Hulton SA, Acquaviva C, et al. Nephrol Dial Transplant. 2012;27(5):1729–1736. 5. Ben-Shalom E, Frishberg Y. Pediatr Nephrol. 2015;30(10):1781–1791. 6. Raju DL, Cantarovich M, Brisson ML, et al. Am J Kidney Dis. 2008;51(1):e1–e5. 7. Bhasin B, Ürekli HM, Atta MG. World J Nephrol. 2015;4(2):235–244. 8. Hoppe B, Beck BB, Milliner DS. Kidney Int. 2009;75(12):1264–1271. 9. Leumann E, Hoppe B. J Am Soc Nephrol. 2001;12(9):1986–1993. 10. El-Reshaid K, Al-Bader D, Madda JP. Saudi J Kidney Dis Transpl. 2016;27(3):606–609. 11. Cochat P. Kidney Int. 1999;55(6):2533–2547. 12. Harambat J, Fargue S, Bacchetta J, et al. Int J Nephrol. 2011;2011:864580. 13. Tintillier M, Pochet JM, Cosyns JP, et al. Clin Nephrol. 2004;62(2):155–157.

PH1-INTR-00020 | January 2025

AN OVERVIEW OF PRIMARY HYPEROXALURIA TYPE 1

PH1 IS A RARE, PROGRESSIVE, INHERITED METABOLIC STONE DISEASE1–3

EARLIER DIAGNOSIS OF PH1 MAY HELP MITIGATE KIDNEY DAMAGE2–6

PH1 is the most common—and most severe—type of PH1,3,7

PH1 can result in irreparable kidney damage1,3

Early diagnosis and intervention are key to mitigating damage2–6

PH1 IS PROGRESSIVE AND SYSTEMIC2,9

See how PH1 can be life-threatening2

EXCESS OXALATE CAN DAMAGE THE KIDNEYS9