Oxalate Excretion Profile in Patients with a Heterozygous Mutation of the AGXT (alanine-glyoxylate Aminotransferase) Gene
- Conditions
- Hyperoxaluria (Disorder)
- Interventions
- Diagnostic Test: Lithiasis assessment
- Registration Number
- NCT06283082
- Lead Sponsor
- Hospices Civils de Lyon
- Brief Summary
Primary hyperoxaluria type I (PH1) is a rare genetic disorder responsible for severe lithiasis leading to progressive deterioration of renal function and end-stage renal failure. PH1 is linked to a deficiency in glyoxylate amino transferase (AGXT), which leads to increased endogenous oxalate synthesis and hyperoxaluria. In the urine, urinary oxalate precipitates with calcium, forming insoluble crystals, leading to lithiasis and the development of nephrocalcinosis.
Non-genetic etiologies of oxalic nephropathy are well known, in particular enteric causes (malabsorptions, bypass, calcium deficiencies, etc.) and sometimes linked to increased oxalate intake in the form of nutritional or vitamin supplements, reinforcing the hypothesis of probably underestimated favouring factors of hyperoxaluria.
Until now, heterozygous patients with a mutation in the AGXT gene were considered asymptomatic. However, there have been several cases of patients with heterozygous AGXT mutations presenting with lithiasis.
Consequently, the characteristics of symptomatic and asymptomatic heterozygous patients will be studied in order to define the elements that would explain the expression of the disease (particularities of the AGXT mutation, presence of another heterozygous mutation or favorable living conditions).
The hypothesis is that there is an increase in hepatic oxalate production in heterozygous patients, which explains why they remain asymptomatic under usual conditions, but could favor stone formation under favorable conditions such as severe calcium deficiency or malabsorption.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 25
- Presenting an heterozygous mutation on AGXT
- Presenting symptoms (presence or history of stones, nephrocalcinosis) or not
- Individuals unable to provide 24-hour urine samples.
- Individuals unable to free up a morning for day hospital appointments
- Individuals deprived of liberty by a judicial or administrative decision.
- Adults under a legal protection measure (guardianship, trusteeship).
- Individuals placed under judicial protection.
- Participants enrolled in another study with an ongoing exclusion period
- Pregnant women.
- Individuals not covered by social security
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Symptomatic subjects with an AGXT heterozygous mutation Lithiasis assessment - Asymptomatic subjects with an AGXT heterozygous mutation Lithiasis assessment -
- Primary Outcome Measures
Name Time Method Urinary oxalate and glycolate excretion At Day 0 Comparison of urinary oxalate and glycolate excretion expressed in mmol/L and mmol/24h of symptomatic versus asymptomatic heterozygous AGXT subjects.
- Secondary Outcome Measures
Name Time Method Predisposing conditions for lithiasis disease At Day 0 Assessing the presence of other gene mutations in lithiasis disease using exome sequencing.
Lithiasis disease severity At Day 0 Assessing the severity of lithiasis by the number and type of crystals.
The prevalence of stones At Day 0 Evaluating the prevalence of stones in asymptomatic heterozygous patients for the AGXT gene using renal ultrasound and through questioning the family history of renal colic or lithiasis and fracture.
Trial Locations
- Locations (1)
CLIMA, pavillon R, Hôpital Edouard Herriot
🇫🇷Lyon, France