Oxalate Excretion Profile in Patients With a Heterozygous Mutation of the AGXT (Alanine-glyoxylate Aminotransferase) Gene (HETEROX)

Oxalate Excretion Profile in Patients With a Heterozygous Mutation of the AGXT (Alanine-glyoxylate Aminotransferase) Gene - Influence of Hygienic and Dietary Conditions and Identification of Favouring Factors by Comparison of Asymptomatic and Symptomatic Patients (Lithiasis or Oxalic Nephropathy)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hyperoxaluria (Disorder)
• Intervention / Treatment: Diagnostic test: Lithiasis assessment

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laurence DERAIN, MD, PhD; Phone Number: +33 04 72 11 91 17; Email: laurence.derain@chu-lyon.fr
• Study Contact Backup: Name: Sandrine Lemoine, MD, PhD; Phone Number: +33 0 4 72 11 02 52; Email: sandrine.lemoine01@chu-lyon.fr

Study Locations

• France
  • Lyon, France, 69003
    • CLIMA, pavillon R, Hôpital Edouard Herriot
    • Contact: Laurence Derain, MD,PhD; Phone Number: +33 04 72 11 91 17; Email: laurence.derain@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Presenting an heterozygous mutation on AGXT
• Presenting symptoms (presence or history of stones, nephrocalcinosis) or not

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Asymptomatic subjects with an AGXT heterozygous mutation	Diagnostic test: Lithiasis assessment; Measurement of oxaluria and glycolaturia on 24 h urine collection, identification of lithiasis disease (biological and ultrasound) and search for lithiasis risk factors.
Active Comparator: Symptomatic subjects with an AGXT heterozygous mutation	Diagnostic test: Lithiasis assessment; Measurement of oxaluria and glycolaturia on 24 h urine collection, identification of lithiasis disease (biological and ultrasound) and search for lithiasis risk factors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary oxalate and glycolate excretion	Comparison of urinary oxalate and glycolate excretion expressed in mmol/L and mmol/24h of symptomatic versus asymptomatic heterozygous AGXT subjects.	At Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The prevalence of stones	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.	At Day 0
Lithiasis disease severity	Assessing the severity of lithiasis by questioning the frequency of stones and need for urological intervention.	At Day 0
Lithiasis disease severity	Assessing the severity of lithiasis by using renal ultrasound (size and number of visualized stones)	At Day 0
Lithiasis disease severity	Assessing the severity of lithiasis by renal function using creatinine level and estimation of glomerular filtration rate (GFR) and Chronic Kidney Disease Epidemiology (CKD-EPI )	At Day 0
Lithiasis disease severity	Assessing the severity of lithiasis by the number and type of crystals.	At Day 0
Predisposing conditions for lithiasis disease	Assessing the role of dietary habits in lithiasis disease by using food diary and particularly Fardelonne questionaire.	At Day 0
Predisposing conditions for lithiasis disease	Assessing the presence of other gene mutations in lithiasis disease using exome sequencing.	At Day 0

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: February 14, 2024
• First Submitted That Met QC Criteria: February 21, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: nutrition; nephropathy; lithiasis; AGXT heterozygous mutation
• Other Study ID Numbers: 69HCL23_0617; ID-RCB (Other Identifier: 2023-A01937-38)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No