Insights into PH1: Understanding disease progression and risk factors in children

Children under 5 years old with Primary Hyperoxaluria Type 1 (PH1) have relatively higher urinary oxalate excretion, putting them at greater risk for nephrocalcinosis and kidney failure compared to older patients with PH1, according to a study, which also found that those with homozygous G170R variants may experience a milder disease progression.

The study focused on children with genetically confirmed PH1 with ≥2 measurements of either urine oxalate-to-creatinine ratio (Uox:cr), 24-hour urine oxalate excretion normalized to body surface area (24-h Uox), or plasma oxalate concentration (Pox).

Out of the 403 patients in the registry, 83 met the inclusion criteria for the study. The researchers observed that Uox:cr decreased rapidly during the first 5 years of life in affected children. Notably, patients with non-G170R AGXT variants had the highest Uox:cr, 24-h Uox, and Pox levels both before and after initiating pyridoxine (B6) treatment.

In comparison, patients with heterozygous G170R variants exhibited Uox:cr levels similar to those with homozygous G170R variants before B6 treatment. However, patients with homozygous G170R variants had the lowest 24-h Uox and Uox:cr levels after B6 treatment.

The study found that urinary oxalate excretion and Pox tended to decrease over time during childhood, with no significant differences in estimated glomerular filtration rate (eGFR) among the different groups.

Reference
Sas DJ, Mara K, Mehta RA, et al. Natural history of urine and plasma oxalate in children with primary hyperoxaluria type 1. Pediatr Nephrol. 2023;doi: 10.1007/s00467-023-06074-x. Epub ahead of print. PMID: 37458799.