From the Research
In patients with Primary Hyperoxaluria Type 1 (PH1), average urinary oxalate levels in 24-hour collections typically exceed 1 mmol/1.73m²/day (approximately 90 mg/1.73m²/day). This is significantly higher than the normal range of less than 0.5 mmol/1.73m²/day (approximately 45 mg/1.73m²/day) 1. Patients with severe PH1 often excrete between 1-3 mmol/1.73m²/day (90-270 mg/1.73m²/day), with some cases reaching even higher levels. These elevated levels result from a genetic defect in the AGXT gene, causing dysfunction of the liver enzyme alanine-glyoxylate aminotransferase (AGT) 2. This enzyme deficiency leads to excessive conversion of glyoxylate to oxalate, which cannot be metabolized further and is excreted in urine. The high urinary oxalate concentration promotes calcium oxalate crystal formation and deposition in the kidneys and urinary tract, leading to recurrent kidney stones, nephrocalcinosis, and progressive kidney damage. Accurate measurement of 24-hour urinary oxalate is essential for diagnosis, monitoring disease severity, and assessing treatment effectiveness in PH1 patients.
Key Points
- Average urinary oxalate levels in PH1 patients exceed 1 mmol/1.73m²/day (approximately 90 mg/1.73m²/day) 1
- Severe PH1 patients often excrete between 1-3 mmol/1.73m²/day (90-270 mg/1.73m²/day) 2
- Elevated urinary oxalate levels result from a genetic defect in the AGXT gene, causing dysfunction of the liver enzyme alanine-glyoxylate aminotransferase (AGT) 1, 2
- Accurate measurement of 24-hour urinary oxalate is essential for diagnosis, monitoring disease severity, and assessing treatment effectiveness in PH1 patients 1, 2
Treatment and Management
Treatment approaches for PH1 have been similar to those for PH2, consisting of intensive hyperhydration, use of crystallization inhibitors, and pharmacologic doses of vitamin B6 (pyridoxine) in responsive patients 2. However, novel therapies based on RNA interference (RNAi) have recently emerged to modulate these pathways, designed to deplete substrate for enzymes upstream and decrease/avoid oxalate production 2. Lumasiran, an RNAi therapy, was approved for the treatment of PH1 in 2020 and has demonstrated a significant reduction of urinary oxalate excretion in PH1 patients 2.
Monitoring and Follow-up
Regular monitoring of urinary oxalate levels is crucial to assess treatment effectiveness and disease severity in PH1 patients 1, 2. Additionally, patients with PH1 should be closely monitored for signs of kidney damage, nephrocalcinosis, and systemic oxalosis, and aggressive treatment should be initiated promptly to prevent long-term complications 1, 2.