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Natural history of urine and plasma oxalate in children with primary hyperoxaluria type 1
David J Sas1,2,3, Kristin Mara4, Ramila A Mehta4
1Division of Pediatric Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. sas.david@mayo.edu.
Insights
Primary hyperoxaluria type 1 (PH1) in children shows higher oxalate levels under age 5, increasing kidney disease risk. Homozygous G170R variants may indicate milder PH1 disease progression.
Area of Science:
- Nephrology
- Genetics
- Pediatric Rare Diseases
Background:
- Primary hyperoxaluria type 1 (PH1) is a severe genetic disorder characterized by excessive hepatic oxalate production.
- This leads to kidney stones, nephrocalcinosis, and progressive chronic kidney disease, particularly in children.
- The natural history of oxalate levels in pediatric PH1 patients remains poorly understood.
Purpose of the Study:
- To investigate the longitudinal changes in urine and plasma oxalate levels in children with PH1.
- To compare oxalate excretion patterns based on different AGXT gene variants (homozygous G170R, heterozygous G170R, non-G170R).
- To assess the impact of pyridoxine (B6) treatment on oxalate levels in these patient groups.
Main Methods:
- Retrospective analysis of data from 83 genetically confirmed PH1 patients under 18 years old.
- Inclusion criteria required at least two pre-18 measurements of urine oxalate-to-creatinine ratio (Uox:cr), 24-h urine oxalate excretion (24-h Uox), or plasma oxalate (Pox).
- Comparison of oxalate values before and after pyridoxine initiation across different AGXT variant groups.
Main Results:
- Urinary oxalate excretion (Uox:cr) decreased significantly in the first five years of life.
- Patients with non-G170R variants consistently showed the highest Uox:cr, 24-h Uox, and Pox.
- Pyridoxine treatment showed a notable effect, with homozygous G170R patients exhibiting the lowest Uox:cr and 24-h Uox post-treatment.
Conclusions:
- Young children (under 5) with PH1 exhibit higher urinary oxalate, posing a greater risk for nephrocalcinosis and kidney failure.
- The homozygous G170R AGXT variant may be associated with a milder form of PH1.
- Oxalate levels generally decrease with age in children with PH1, with variations observed based on genotype and pyridoxine treatment.
Background:
Primary hyperoxaluria type 1 (PH1) is a rare, severe genetic disease causing increased hepatic oxalate production resulting in urinary stone disease, nephrocalcinosis, and often progressive chronic kidney disease. Little is known about the natural history of urine and plasma oxalate values over time in children with PH1.
Methods:
For this retrospective observational study, we analyzed data from genetically confirmed PH1 patients enrolled in the Rare Kidney Stone Consortium PH Registry between 2003 and 2018 who had at least 2 measurements before age 18 years of urine oxalate-to-creatinine ratio (Uox:cr), 24-h urine oxalate excretion normalized to body surface area (24-h Uox), or plasma oxalate concentration (Pox). We compared values among 3 groups: homozygous G170R, heterozygous G170R, and non-G170R AGXT variants both before and after initiating pyridoxine (B6).
Results:
Of 403 patients with PH1 in the registry, 83 met the inclusion criteria. Uox:cr decreased rapidly over the first 5 years of life. Both before and after B6 initiation, patients with non-G170R had the highest Uox:cr, 24-h Uox, and Pox. Patients with heterozygous G170R had similar Uox:cr to homozygous G170R prior to B6. Patients with homozygous G170R had the lowest 24-h Uox and Uox:cr after B6. Urinary oxalate excretion and Pox tend to decrease over time during childhood. eGFR over time was not different among groups.
Conclusions:
Children with PH1 under 5 years old have relatively higher urinary oxalate excretion which may put them at greater risk for nephrocalcinosis and kidney failure than older PH1 patients. Those with homozygous G170R variants may have milder disease. A higher resolution version of the Graphical abstract is available as Supplementary information.
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