Genetic of Chronic Kidney Disease and Gout in New Caledonia (CALEDGOUTCKD)

Genetic of Chronic Kidney Disease and Gout : Analysis of Melanesian Families From New Caledonia

The goal of this research is to study the associations of genetic variants of gout and kidney failure, which are very common in the Melanesian population in New Caledonia

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency, Chronic; Gout
• Intervention / Treatment: Other: Epidemiological study

Detailed Description

Gout is a chronic pathology linked to the deposition in the tissues of monosodium urate (MSU) crystals, secondary to hyperuricemia (high blood levels of urate). Gout causes very painful joint attacks that are first acute and then lead to chronic pain, and disabling deforming manifestations called tophus. The disease is strongly associated with cardiovascular comorbidities and chronic renal failure.

In New Caledonia, the prevalence of chronic kidney disease (CKD) (according to the glomerular filtration rate (GFR) < 60 ml/min) was of 7.4% in 2015 (according to the epidemiological study "Barometer Health 2015"). In the Loyalty Islands, which has overall significantly more Melanesian population, a local database showed that in 2018 the prevalence of patients having at least one blood test reporting kidney disease (GFR CKD< 60 ml/min) and seen at least once in the previous two years was as follows:

• 7.7% in Lifou (9,200 inhabitants)
• 8.4% in Maré (5,700 inhabitants)
• 9.1% in Ouvéa (3,400 inhabitants) In summary, inflammatory diseases such as CKD and gout have high prevalence in New Caledonia and the Loyalty Islands, and constitute a major health issue. Although the high prevalence of these diseases is probably due in part to non-genetic factors (environment, diet, etc.), it is likely, given the demographic history of this region, that undetected genetic risk alleles among the Melanesian population contribute to the appearance and progression of diseases. Performing genetic and epidemiological studies in an as yet understudied region is essential to identify these variants, which could lead to improved diagnoses and health outcomes.

• Study Type: Interventional
• Enrollment (Actual): 1858
• Phase: Not Applicable

Contacts and Locations

Study Locations

• New Caledonia
  • Nouméa, New Caledonia
    • Medical Center of Wé (Lifou Island)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Criteria common to the 3 cohorts :

- Consenting to participate in the study and having signed the informed consent

- Claiming to be of Melanesian ethnicity

1. Patients with gout :

   • Age: 18 - 70 years old

   • To be included in the study, a patient with a diagnosis of gout in his medical file or declaring to have gout will have to satisfy to the ACR/EULAR (ref) classification criteria :

     1. have had at least one episode of swelling, pain spontaneous, or triggered by pressure, of a joint peripheral or a bursa AND evidence of sodium urate crystals in a joint or bursitis symptomatic or by puncture of a tophus reported in his medical file.
     2. Or Score > or =8 according to ACR/EULAR clinical criteria

2. Patients with CKD

   • Age: 18 - 70 years old

   • Patients on dialysis or CKD clinically diagnosed on the basis of:

     1. Markers of kidney damage (one or more) : Albuminuria (ACR ≥ 30 mg/g), Urinary sediment abnormalities (e.g., casts urinary), Electrolyte abnormalities and other, abnormalities due to tubular disorders (eg, hyperkalemia), abnormalities detected by histology, structural abnormalities detected by imaging (e.g.,USG), history of kidney transplantation
     2. Decreased kidney function: GFR < 60 ml/min/1.73 m² (calculated according to the Chronic Kidney Disease - EPIdemiology formula: CKD-EPI)

3. Controls cohort

   • Absence of gout or CKD
   • Age: 30 - 80 years old

Exclusion Criteria:

• Pregnant women
• Individuals under guardianship / curatorship / judicially incapacitated

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with gout; Patients aged 18-70 with gout diagnosis in their medical record or claiming to have gout according to ACR/EULAR (American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria.	Other: Epidemiological study; Sociodemographic data collection, treatments collection, physical assessment, clinical examination and physical and biological measurements, biological evaluation (blood and urine samples), CKD-specific clinical features collection, gout-specific clinical features collection, clinical characteristics specific to chronic diseases, questionnaires (Health Assessment Questionnaire (HAQ-II), EuroQol (EQ)-5D-5L, joint pain, state of health, diet and physical activity, access to care, addictions, pain scale (EVA), personal and family history)
Experimental: Patients with CKD; Patients aged 18-70, in dialysis or with CKD clinically diagnosed on the basis of markers of kidney damage or decreased kidney function. Patients will be recruited in dialysis centers of Wé and Maré and during the monthly nephrology consultations in medical centers.	Other: Epidemiological study; Sociodemographic data collection, treatments collection, physical assessment, clinical examination and physical and biological measurements, biological evaluation (blood and urine samples), CKD-specific clinical features collection, gout-specific clinical features collection, clinical characteristics specific to chronic diseases, questionnaires (Health Assessment Questionnaire (HAQ-II), EuroQol (EQ)-5D-5L, joint pain, state of health, diet and physical activity, access to care, addictions, pain scale (EVA), personal and family history)
Placebo Comparator: Control group; Persons aged 30-80 without gout or CKD. The recruitment will be done among people visiting the medical centers of Lifou and Maré for administrative or vaccination reasons.	Other: Epidemiological study; Sociodemographic data collection, treatments collection, physical assessment, clinical examination and physical and biological measurements, biological evaluation (blood and urine samples), CKD-specific clinical features collection, gout-specific clinical features collection, clinical characteristics specific to chronic diseases, questionnaires (Health Assessment Questionnaire (HAQ-II), EuroQol (EQ)-5D-5L, joint pain, state of health, diet and physical activity, access to care, addictions, pain scale (EVA), personal and family history)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genome-wide association study (GWAS) in gout	GWAS is a research approach used to identify genomic variants that are statistically associated with a risk for a disease or a particular trait. The method involves surveying the genomes of many people, looking for genomic variants that occur more frequently in those with a specific disease or trait compared to those without the disease or trait. Once such genomic variants are identified, they are typically used to search for nearby variants that contribute directly to the disease or trait.	8 months
Phenome-wide association studies (PheWAS) in gout	PheWAS will be used to analyze many phenotypes compared to a single genetic variant (or other attribute).	8 months
GWAS in CKD	Genome-wide association study (GWAS) and Phenome-wide association studies (PheWAS) will be used. GWAS is a research approach used to identify genomic variants that are statistically associated with a risk for a disease or a particular trait. The method involves surveying the genomes of many people, looking for genomic variants that occur more frequently in those with a specific disease or trait compared to those without the disease or trait. Once such genomic variants are identified, they are typically used to search for nearby variants that contribute directly to the disease or trait. PheWAS will be used to analyze many phenotypes compared to a single genetic variant (or other attribute).	8 months
PheWAS in CKD	PheWAS will be used to analyze many phenotypes compared to a single genetic variant (or other attribute).	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomic profile in gout	Metabolomics profiling will be conducted using ultrahigh-performance liquid chromatography-tandem mass-spectrometry by the metabolomics provider Metabolon Inc. (USA) on fasting serum samples from participants. The metabolomic dataset measured by Metabolon includes known metabolites containing the following broad categories - amino-acids, peptides, carbohydrates, energy intermediates, lipids, nucleotides, cofactors and vitamins, and xenobiotics.	8 months
Metabolomic profile in CKD	Metabolomics profiling will be conducted using ultrahigh-performance liquid chromatography-tandem mass-spectrometry by the metabolomics provider Metabolon Inc. ( USA) on fasting serum samples from participants. The metabolomic dataset measured by Metabolon includes known metabolites containing the following broad categories - amino-acids, peptides, carbohydrates, energy intermediates, lipids, nucleotides, cofactors and vitamins, and xenobiotics.	8 months
GWAS and severity of CKD according to glomerular filtration rate (GFR)	GWAS will be used to identify genomic variants that are statistically associated with severity. Stage of severity according to GFR (mL/min/1.73m2): Mild renal impairment with normal or increased filtration : Over 90; Mild decrease in renal function : 60-89; Moderate decrease in renal function : 30-59; Severe decrease in renal function : 15-29; Renal failure: Less than 15 (or dialysis)	8 months
GWAS and severity of gout	GWAS will be used to identify genomic variants that are statistically associated with severity. Severity will be defined using four binary variables: number of attacks (cutoff six attacks per year), presence of clinical tophus (yes or no), uric acid level (>80 mg/L or 480 micromol/L) and age of onset (<30 years) .	8 months
Relation between CKD and sex	Relation between CKD and sex (Male/ Female)	8 months
Relation between gout and sex	Relation between gout and sex (Male/ Female)	8 months
Relation between CKD and age	Relation between CKD and age	8 months
Relation between gout and age	Relation between gout and age	8 months
Relation between CKD and Body Mass Index (BMI)	Relation between CKD and Body Mass Index (BMI) in kg/m^2	8 months
Link between gout and Body Mass Index (BMI)	Link between gout and Body Mass Index (BMI) in kg/m^2	8 months
Relation between CKD and the Body Fat Percentage	Relation between CKD and the Body Fat Percentage in Percentage (%)	8 months
Relation between gout and the Body Fat Percentage	Relation between gout and the Body Fat Percentage in Percentage (%)	8 months
Relation between CKD and Muscle Mass Percentage	Relation between CKD and Muscle Mass Percentage in Percentage (%)	8 months
Relation between gout and Muscle Mass Percentage	Relation between gout and Muscle Mass Percentage in Percentage (%)	8 months
Relation between CKD and Basal Metabolism	Relation between CKD and Basal Metabolism in Joules	8 months
Relation between gout and Basal Metabolism	Relation between gout and Basal Metabolism in Joules	8 months
Relation between CKD and Visceral Fat Percentage	Relation between CKD and Visceral Fat Percentage in Percentage	8 months
Relation between gout and Visceral Fat Percentage	Relation between gout and Visceral Fat Percentage in Percentage	8 months
Relation between CKD and height	Relation between CKD and height in meters	8 months
Relation between gout and height	Relation between gout and height in centimeters	8 months
Relation between CKD and waist size	Relation between CKD and waist size in centimeters	8 months
Relation between gout and waist size	Relationbetween gout and waist size in centimeters	8 months
Relation between CKD and hip circumference	Relation between CKD and hip circumference in centimeters	8 months
Relation between gout and hip circumference	Relation between gout and hip circumference in centimeters	8 months
Relation between CKD and waist/hip ratio	Relation between CKD and waist/hip ratio	8 months
Relation between gout and waist/hip ratio	Relation between gout and waist/hip ratio	8 months
Mendelian randomization	Mendelian randomization uses measured variation in genes to interrogate the causal effect of an exposure on comorbidities development	8 months

Collaborators and Investigators

• Sponsor: Lille Catholic University
• Collaborators: Variant Bio, Inc.
• Investigators: Principal Investigator: Thomas BARDIN, Hopital Lariboisiere

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): April 30, 2024

Study Registration Dates

• First Submitted: October 18, 2022
• First Submitted That Met QC Criteria: November 2, 2022
• First Posted (Actual): November 7, 2022

Study Record Updates

• Last Update Posted (Estimated): November 27, 2024
• Last Update Submitted That Met QC Criteria: November 25, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Gout; New Caledonia; Renal Insufficiency Chronic
• Additional Relevant MeSH Terms: Crystal Arthropathies; Urogenital Diseases; Musculoskeletal Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Arthritis; Joint Diseases; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Gout; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: RC-P00116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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