Kidney Stone and Doctor With Family - Primary Hyperoxaluria Type 1 (PH1) Testing
Kidney Stone and Doctor With Family - Primary Hyperoxaluria Type 1 (PH1) Testing

TESTING FOR PRIMARY HYPEROXALURIA TYPE 1 (PH1)

Diagnosing and managing PH1 as early as possible may mitigate damage.1-5 Oxalate level evaluation and genetic testing are current approaches used to help inform a PH1 diagnosis.1,2

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GIVEN THE PROGRESSIVE, UNPREDICTABLE NATURE OF PH1, EARLY DIAGNOSIS IS CRITICAL5,6

If PH1 is suspected, some common methods seen in clinical practice to help test for the disease are listed below.

This testing information is provided for educational purposes only and is not intended to replace the independent medical judgment of any healthcare professional.

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Diagnosing PH1 Diagram

Adapted from Groothoff JW, et al. Nat Rev Nephrol. 2023.

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MEASURING OXALATE LEVELS

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In patients with preserved kidney function:

24-HOUR URINE TEST1,2,7,*

  • Normal UOx level (all ages):
    <45 mg (<0.50 mmol) /1.73 m2/24 hours8
  • Spot testing can be used when 24-hour urine test is not possible6

In PH1, UOx levels are often >2 times higher than the upper limit normal.9

In patients with impaired kidney function:

PLASMA OXALATE MEASUREMENT2,3,6

  • Normal plasma oxalate level: ≤2.0mcmol/L†,10

Substantially elevated levels are typical when eGFR <30 mL/min/1.73 m2. Levels >50 μmol/L are suggestive of PH1.5

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In patients with elevated UOx or plasma oxalate levels:

GENETIC TESTING

Identifying AGXT gene mutations with genetic testing can help confirm a PH1 diagnosis with high sensitivity and specificity.2,11

It is recommended to screen family members of a patient with PH1, especially siblings.2,6

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ERKNet and OxalEurope guidelines 2023 recommend that all patients with suspected PH1 undergo genetic testing7

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  • Genetic assessment remains the gold standard of diagnosing PH1 in patients, as patients with certain PH1 genotypes respond strongly to pyridoxine, which can be difficult to measure7
  • ERKNet and OxalEurope 2023 guidelines also express the importance of genetic counselling for couples in which both partners are carriers of mutations that predispose to PH1, to enable early diagnosis and management of affected children7
  • Where genetic testing is unavailable, the guidelines recommend biochemical assessment of urinary oxalate in a 24-hour sample7

eGFR, estimated glomerular filtration rate.

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WHERE TO TEST FOR PH1

France:

Centres de Référence des maladies rénales rares (Filiére ORKiD):

MARHEA – Paris
01 44 49 43 82
https://www.filiereorkid.com/crmr_marhea/
Néphrogones - Lyon
04 27 85 61 28
https://www.chu-lyon.fr/service-de-nephrologie-rhumatologie-dermatologie-pediatriques
SoRare – Toulouse
05 34 55 86 64 (enfants) - 05 61 32 32 93 (adultes)
https://maladiesrares-necker.aphp.fr/marhea/

Italy:

Genilam

Genilam Italy

Genetic testing can detect certain genetic mutations in patients, and help doctors provide a more accurate diagnosis.
Access the Genilam service for Primary Hyperoxaluria Type 1

SPAIN:

Diagnostic tests can be requested free of charge by a healthcare professional. In case of suspicion of hyperoxaluria, the health professional can request the test by writing an email to this address proyecto.exhplora@vallhebron.cat

UK:

Commissioned and paid for by the National Health Service (NHS) via Trust mapped Genomic Laboratory Hub.

Primary Hyperoxaluria Genetics

  • Whole gene sequencing for mutations in the AGXT (PH1), GRHPR (PH2) and HOGA1 (PH3) genes
  • Typical Turnaround Time Step one test (screening for commonest mutations) 10 days; Whole gene sequencing 28 days
  • Contact Hyperoxaluria Rare Disease Collaborative Network for advice

R257 Unexplained young onset end-stage renal disease8

  • Testing Criteria
    • End-stage renal disease developing under the age of 36, with no identifiable cause detectable by renal biopsy, biochemistry, imaging or clinical assessment
    • Use of this test in young adults over the age of 36 may be appropriate after expert clinical review, if there is strong clinical suspicion of a monogenic disorder

  • Testing Criteria for Semi-Rapid Testing

    • Acutely unwell children or adults where monogenic young onset end-stage renal disease is considered highly likely to be the primary cause of the phenotype in the patient.
    • Where testing will provide an immediate change to treatment or clinical management for the patient eg. To inform a decision about renal transplant, therapeutic intervention or prenatal testing for an ongoing at-risk pregnancy.
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Early Diagnosis can mitigate damage1-5

https://vimeo.com/358271441
Primary Hyperoxaluria Type 1 (PH1) in Children - Parents' Caregiving Perspectives - Video Thumbnail

Natalie and Jared share the hope they have for their children with PH1.

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