Primary Hyperoxaluria (PH) is a family of rare genetic disorders of the liver in which enzyme deficiencies cause an accumulation of oxalate in the kidneys and other organs.1
When too much oxalate accumulates, it may become toxic to the kidneys, as it binds with calcium to form calcium oxalate (CaOx) crystals. These crystals aggregate to form stones in the kidneys and the urinary tract. As the disease severity increases over time, progressive kidney damage can lead to end-stage renal disease, as well as to the potential deposition of oxalate throughout the body (including the heart, skin, eyes and bones), which is a life-threatening condition.1,2
There are three main types of PH, which are characterized based on the specific gene and enzyme affected1:
Primary Hyperoxaluria Type 1 (PH1)
- This type is caused by mutations in the AGXT gene and is the most severe and most common of the three types, accounting for an estimated 70%-80% of all people diagnosed with PH.1
Primary Hyperoxaluria Type 2 (PH2)
- This type is caused by mutations in the GRHPR gene and is thought to account for approximately 10% of diagnosed cases.1
Primary Hyperoxaluria Type 3 (PH3)
- This type is caused by mutations in the HOGA1 gene. PH3 is less widely studied than PH1 and PH2 due to very few cases having been reported.1
It is important to note that the estimated prevalence based on genetic studies is higher than the diagnosed prevalence of these conditions, due to misdiagnosis or underdiagnosis. The relative proportion of PH1, PH2, and PH3 from a genetic prevalence perspective is also different from diagnosed prevalence.3
In separate studies...
In many people, kidney stones may be the first sign of PH. However,
as PH is a rare disease, symptoms can often go unrecognized or be
confused with the signs of other disorders, leading to a delay in
diagnosis. Family members diagnosed with PH with the same genetic
mutation may present symptoms and timing of the symptoms differently.
Most patients with PH live with the uncertainity of recurring kidney
stones, progressive kidney damage, or effects on multiple organs,
which may require dialysis or a dual liver-kidney
transplant.1,8
Methods to help diagnose PH
may include1,9:
- Genetic testing
- Investigation of symptoms, including kidney stones and their composition
- Analysis of patient history
- Measurement of urine oxalate levels
- Measurement of plasma oxalate levels in patients with kidney failure
If you are a healthcare professional, we offer a no-charge
genetic and PH-specific metabolite testing program that can help
identify the potential underlying cause of conditions that can cause
kidney stones (RKS), including PH.
Learn
more about the NovoDETECTTM Program here.
PH not only affects those living with it, but also their families and
caregivers.7 For people living with PH, hyperhydration is
often used to help reduce crystal aggregation and stone formation.
Ensuring water intake is high enough to dilute oxalate can be an
overwhelming burden, with some children requiring a gastronomy tube to
maintain this fluid intake.9 Hyperhydration can have a
significant impact on a patient’s quality of life, causing
interruptions at school, work and social events, as well as sleep
loss.7
In addition, surgical procedures are often required to remove kidney stones, which may pose a great burden to individuals.8
Diagnosis is the first step to managing PH. The earlier it is identified, the sooner changes to lifestyle can be made and management strategies can be implemented to help limit damage to the kidneys and other organs.10
Bringing more awareness and education around PH is critical to ensure timely diagnosis and management.
Explore more on our research technologies, like RNA interference
(RNAi), a technology that silences the genes that contribute to
disease.
Explore more on RNA interference (RNAi).
1. Primary Hyperoxaluria - Symptoms, Causes, Treatment. National Organization for Rare Disorders. January 23, 2024. Accessed March 13, 2024. https://rarediseases.org/rare-diseases/primary-hyperoxaluria/
2. Lorenzo V, Torres A, Salido E. Primary hyperoxaluria. Nefrologia. 2014;34(3):398-412. doi:10.3265/Nefrologia.pre2014.Jan.12335
3. Hopp K, Cogal AG, Bergstralh EJ, et al. Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria. Journal of the American Society of Nephrology. 2015;26(10):2559-2570. doi:10.1681/ASN.2014070698
4. Harambat J, Fargue S, Acquaviva C, et al. Genotype–phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome. Kidney International. 2010;77(5):443-449. doi:10.1038/ki.2009.435
5. Karafilidis J, Fazio-Eynullayeva E, Mucha L, Landsman-Blumberg PB, Kuranz SP. Real-World Healthcare Utilization and Clinical Markers Preceding Dialysis in Patients with Primary Hyperoxaluria (PH) in the United States. In: Journal of the American Society of Nephrology. Vol 32. American Society of Nephrology; 2021:PO1317. https://www.asn-online.org/education/kidneyweek/2021/program-abstract.aspx?controlId=3604122
6. Hoppe B, Langman CB. A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria. Pediatric Nephrology. 2003;18(10):986-991. doi:10.1007/s00467-003-1234-x
7. Lawrence JE, Wattenberg DJ. Primary Hyperoxaluria: The Patient and Caregiver Perspective. CJASN. 2020;15(7):909-911. doi:10.2215/CJN.13831119
8. Milliner DS, McGregor TL, Thompson A, et al. End Points for Clinical Trials in Primary Hyperoxaluria. CJASN. 2020;15(7):1056-1065. doi:10.2215/CJN.13821119
9. Groothoff JW, Metry E, Deesker L, et al. Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope. Nat Rev Nephrol. 2023;19(3):194-211. doi:10.1038/s41581-022-00661-1
10. Primary Hyperoxaluria Type 1. National Kidney Foundation. March 29, 2021. Accessed August 10, 2024. https://www.kidney.org/atoz/content/primary-hyperoxaluria-type-1