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Medical Information | Non-US Health Care Professionals

Identifying and diagnosing primary hyperoxaluria type 1

Symptom presentation and disease progression of primary hyperoxaluria type 1 can be unpredictable, so early diagnosis and management are critical.1

The majority of patients with PH1 remain undiagnosed2

While PH1 affects ~2700 people in the US based on genetic studies,* approximately 800 are diagnosed based on clinical studies.2,3

*Estimated US prevalence from genetic studies.

Many patients with PH experience a delay in diagnosis from initial symptom onset4,5

In a study, 42% of patients with PH experienced a significant delay in diagnosis6
Patients experienced 3.4 ± 5.4 years between first symptom presentation and diagnosis.

A separate study found that ~5% were only diagnosed after kidney transplant
19% diagnosed after transplant were not diagnosed until after first transplant failure.7

One study reported that 27% of patients were diagnosed at ESRD (end-stage renal disease)
with delay of 3.5 years after symptom onset.5

PH=primary hyperoxaluria.

Diagnostic methods

The diagnostic methods for PH typically include: 

24-hour urine collection (normal kidney function)8,9

  • elevated urinary oxalate on at least 2 assessments, >0.7 mmol (64 mg)/24 h

Spot urine collection8,10

  • oxalate: creatinine ratio > normal for age

Plasma collection (eGFR <30 mL/min/1.73 m2)8,11

  • plasma oxalate >20 µmol/L

Kidney stone analysis8,12

  • PH1: characteristic morphology and >95% 
calcium oxalate monohydrate
  • PH2 and PH3: stone burden and speed of recurrence

Genetic testing for known mutations8

  • AGXT mutations: PH1
  • GRHPR mutations: PH2
  • HOGA1 mutations: PH3

Rule out secondary causes8

  • enteric causes (eg, chronic pancreatitis, cystic fibrosis, inflammatory bowel syndrome, bariatric surgery)
  • very high-oxalate, low-calcium diet
  • infant with prematurity

eGFR=estimated glomerular filtration rate.

Genetic testing for PH1

Analyzing specific genes is crucial for an accurate diagnosis in patients with kidney-stone diseases with clinical overlap in symptoms, as it helps identify disease-causing mutations. This allows for patient management that may reduce recurrent symptoms or progression to end-stage kidney disease.8

ICD-10 code for your primary hyperoxaluria patients

Note: One ICD-10 code covers all 3 types of PH.

ICD Indication

ICD-10 Code

Primary hyperoxaluria (PH), all types 

E72.53 

Know the warning signs of PH1 

PH can be challenging to diagnose because it is a rare disease, has wide clinical variability, and has overlapping symptoms with other genetic kidney stone disorders.12 If your patient has one or more of the symptoms described below, screening for primary hyperoxaluria should be performed.

Family history of kidney or bladder stones
Many patients are asymptomatic for years, with 18% of people with PH1 being diagnosed by familial screening before they show any symptoms.11,13

A single pediatric kidney stone
Children should not develop bladder or kidney stones, and the presence of even a single kidney stone in an infant or child should immediately raise suspicion of a genetic condition like primary hyperoxaluria.11,14

Recurring kidney stones in adults
A single kidney stone in an adult is not uncommon, but recurring kidney stones can be indications of an underlying metabolic disorder or genetic disease.11

Chronic kidney disease (CKD) with unknown etiology
Suspect primary hyperoxaluria when a patient presents with reduced renal function combined with nephrocalcinosis or a high occurrence of kidney stones.14

Nephrocalcinosis
Both pediatric and adult patients with early signs of nephrocalcinosis should be screened for primary hyperoxaluria.14

Systemic oxalosis
Kidney failure can be the first clinical indication of primary hyperoxaluria in some patients, even in infancy. When patients are in kidney failure, calcium oxalate can deposit in tissues throughout the body. Systemic oxalosis can impact bone, skin, heart, and eye health.9,15

End-stage renal disease (ESRD)
Studies have shown that many people are not diagnosed with PH until they are in ESRD (35% of all patients with PH1), although these patients often had earlier symptoms that went unrecognized, such as recurring kidney stones. About 59% of people diagnosed with PH1 as adults are in ESRD at the time of diagnosis.5,13,16

Failure to thrive, ESRD, severe retinal abnormalities, or vision loss in infants 
In a study, infantile onset was shown to occur in 18% of patients with PH1. Infants with this severe form present with end-stage kidney disease, failure to thrive, severe retinal abnormalities, and vision loss during their first year.16 18

Elevated urinary oxalate (UOx) levels
Even in the absence of stones, elevated oxalate levels and oxalate buildup can cause progressive kidney damage that can lead to nephrocalcinosis and end-stage kidney disease (ESKD).9

Access diagnosis and management recommendations

View the latest best practice recommendations for primary hyperoxaluria diagnosis and management.

References:

  1. Fargue S, Harambat J, Gagnadoux MF, et al. Effect of conservative treatment on the renal outcome of children with primary hyperoxaluria type 1. Kidney Int. 2009;76(7):767-773. doi:10.1038/ki.2009.237
  2. Hopp K, Cogal AG, Bergstralh EJ, et al. Phenotype-genotype correlations and estimated carrier frequencies of primary hyperoxaluria. J Am Soc Nephrol. 2015;26(10):2559-2570. doi:10.1681/ASN.2014070698
  3. U.S. and World Population Clock. United States Census Bureau. Accessed January 10, 2025. https://www.census.gov/popclock/
  4. Hoppe B, Beck BB, Milliner DS. The primary hyperoxalurias. Kidney Int. 2009;75(12):1264-1271. doi:10.1038/ki.2009.32
  5. Zhao F, Bergstralh EJ, Mehta RA, et al. Predictors of incident ESRD among patients with primary hyperoxaluria presenting prior to kidney failure. Clin J Am Soc Nephrol. 2016;11(1):119-126. doi:10.2215/CJN.02810315
  6. Hoppe B, Langman CB. A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria. Pediatr Nephrol. 2003;18(10):986-991. doi:10.1007/s00467-003-1234-x
  7. Bergstralh EJ, Monico CG, Lieske JC, et al. Transplantation outcomes in primary hyperoxaluria. Am J Transplant. 2010;10(11):2493-2501. doi:10.1111/j.1600-6143.2010.03271.x
  8. 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
  9. Milliner DS, Harris PC, Sas DJ, Cogal AG, Lieske JC. Primary hyperoxaluria type 1. 2002 Jun 19. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025.
  10. Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med. 2013;369(7):649-58. doi:10.1056/NEJMra1301564
  11. Edvardsson VO, Goldfarb DS, Lieske JC, et al. Hereditary causes of kidney stones and chronic kidney disease. Pediatr Nephrol. 2013;28(10):1923-42. doi:10.1007/s00467-012-2329-z
  12. Cochat P, Hulton SA, Acquaviva C, et al. Primary hyperoxaluria type 1: indications for screening and guidance for diagnosis and treatment. Nephrol Dial Transplant. 2012;27(5):1729-36. doi:10.1093/ndt/gfs078
  13. Mandrile G, van Woerden CS, Berchialla P, et al. Data from a large European study indicate that the outcome of primary hyperoxaluria type 1 correlates with the AGXT mutation type. Kidney Int. 2014;86(6):1197-204. doi:10.1038/ki.2014.222
  14. Bhasin B, Ürekli HM, Atta MG. Primary and secondary hyperoxaluria: understanding the enigma. World J Nephrol. 2015;4(2):235-44. doi:10.5527/wjn.v4.i2.235
  15. 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 Int. 2010;77(5):443-9. doi:10.1038/ki.2009.435
  16. van Woerden CS, Groothoff JW, Wanders RJ, Davin JC, Wijburg FA. Primary hyperoxaluria type 1 in The Netherlands: prevalence and outcome. Nephrol Dial Transplant. 2003;18(2):273-9. doi:10.1093/ndt/18.2.273
  17. Birtel J, Herrmann P, Garrelfs SF, et al. The ocular phenotype in primary hyperoxaluria type 1. Am J Ophthalmol. 2019;206:184-191. doi:10.1016/j.ajo.2019.04.036
  18. Frishberg Y, Rinat C, Shalata A, et al. Intra-familial clinical heterogeneity: absence of genotype-phenotype correlation in primary hyperoxaluria type 1 in Israel. Am J Nephrol. 2005;25(3):269-75. doi:10.1159/000086357