Diabetes, Diabetic Kidney Disease, Diabetic Nephropathies, Healthy Volunteer, Hypoxia
Conditions
Brief summary
Diabetes mellitus is a non-transmissible disease whose incidence is growing worldwide . This pathology is defined by a chronic hyperglycaemia linked to a deficiency of either insulin secretion or its action or both. This increased prevalence is linked to the growing of the obese population on one hand, and to the ageing of the population, on the other hand, which is associated with an increased prevalence of metabolic diseases. The number of patients with diabetes, particularly type 2 diabetes (T2D) is regularly increasing. In France, the prevalence of diabetes is 4- 6% of the adult population. Diabetic kidney disease (DKD) is a growing public health problem and therefore constitutes a major factor in progressive kidney disease. DKD has become the leading cause of end stage kidney disease (ESKD), requiring dialysis or transplantation. Current routine screening for DKD is limited to detecting of impaired glomerular filtration rate (GFR) and/or elevated albuminuria, typically manifests in later stages of DKD. Therefore, the current methods to screen for DKD lack the resolution to capture the earliest functional changes associated with DKD. Chronic renal hypoxia plays a crucial role in the development and progression of DKD and may affect Renal hemodynamic. The aim to assess the feasibility of the measure of hypoxa-induced renal hemodynamics parameters.
Interventions
OTHERHypoxia administration study group
Acute 2-hour hypoxia (14.5%FiO2 corresponding to 3000m altitude)
COMBINATION_PRODUCTRenal clairance study
Assessment of renal clearance by measuring Glomerular Filtration Rate (GFR) after two agents infusion: * Aminohippurate Sodium (or or para-aminohippuric acid \[PAH\]) Inj 20% Diagnostic agent used to measure effective renal plasma flow (ERPF) * Iohexol Inj 300 MG/ML Diagnostic agent used to measure glomerular filtration rate (GFR)
Sponsors
Poitiers University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
It is a descriptive, prospective, open label, single centre, pilot study. This research aim to better understand the effect of hypoxia on intrarenal hemodynamic parameters of 3 groups : Group 1: Healthy volunteers Group 2: Patient with Type 2 Diabetes (DT2) without Diabetic Kidney Disease (DKD) Group 3: Patient with T2D and DKD
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
For all participant : 1. No history of respiratory diseases 2. Affiliated person or beneficiary of the French social security scheme. 3. signed informed consent Group 1 ( For healthy volunteers): 1. \[18; 40\] years old 2. No history of diabetes 3. No acute/long term \> 3 months drug use except contraception 4. BMI: \[18,5 - 29,9\]kg/m2 5. eGFR \> 60ml/min/1.73m2 6. Normal to midly increased albuminuria: defined as ACR \< 3 mg/mmol For all the patients with T2D (group 2 and 3): 1. Diagnosed T2D according to ADA criteria 2. \[35; 75\] years old 3. Stable treatment of diabetes and/or antihypertension for at least 2 months prior to inclusion 4. No proliferative diabetic retinopathy Group 2 - For patients with T2D and no DKD: * eGFR \> 60ml/min/1.73m2 and * Normal to midly increased albuminuria: defined as ACR \< 3 mg/mmol Group 3 - For patients with DKD: * eGFR \[45-60 ml/min/1.73m2\] and/or * Moderately to severely increased ACR ≥ 3 mg/mmol
Exclusion criteria
For all participants: 1. Active smoking 2. Contraindication to any of the agent (PAH, or iohexol or gadolinium) used in the study. 3. Contraindication to cardiac MRI, renal MRI, respiratory tests, 4. History acute coronary syndrome or coronary revascularization 5. Recent (\<6 months) history of: Heart failure requiring hospitalisation or Stroke or transient ischemic neurologic disorder 6. Severe unstable hypertension (≥180 mmHg systolic or ≥110 mmHg diastolic blood pressure) 7. Resting oxygen saturation \<95% at baseline 8. Any concomitant disease or condition that may interfere with the safety or the possibility for the patient to comply with or complete the study protocol. 9. History of severe mountain sickness (dizziness, headache, nausea/vomiting and incapaciting fatigue) 10. Consumption of SGLT2 inhibitors 11. Concurrent participation in another clinical research study 12. Pregnant or breastfeeding women, women of childbearing age who do not have effective contraception 13. Persons benefiting from enhanced protection under french national law 14. Persons under psychiatric care who are unable to give their consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glomerular Filtration Rate | 5 hours | Measured by Iohexol Clearance |
| Effective Renal Plasma Flow (ERPF) | 5 hours | Measured by PAH clearance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| blood pressure | 5 hours | mean arterial pressure |
| Lake Louise Questionnaire | 5 hours | The Lake Louise Scoring was developed to assess the symptoms of acute mountain sickness in adults. It consist of 4 questions, each rated on a likert-type scale with 0-3 response options. Lower scores men a better outcome. |
| Oxygen saturation | 5 hours | SpO2 |
| heart rate | 5 hours | heart rate |
| circulating and urinary mitochondrial metabolites | 8 days | To investigate change of blood or urine metabolites : 2-ethyl 3-OH propionate, 3-hydroxy propionate, 3-hydroxy isovalerate, 3-methyl-crotonyl glycine, 3-hydroxy isobutyrate, Tiglyglycine, Aconitic acid, Citric acid, Glycolic acid, Homovanillic acid, Uracil, 3-methyl adipic acid. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Renal Oxygenation Availability | 60 minutes | Blood oxygen level dependent (BOLD) MRI |
| Cardiac Oxygenation Availability | 60 minutes | Blood oxygen level dependent (BOLD) MRI |
Countries
France
Contacts
Primary ContactEmilie RABOIS, MSc
Backup ContactCéline DELETAGE METREAU, PhD
Outcome results
None listed