kidney disease Kidney hypoxia
Conditions
Interventions
None listed
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Group 1: Patients with obesity and hyperfiltration • ; man or women aged >=18 years and =35 • eGFR>90 ml/min calculated as by CKD-EPI • Provision of signed and dated, written informed consent prior to any study specific procedures • Hypertension should be controlled, i.e., =18 years and =18,5 and =18 years and =45mmol/ mol and =25 • eGFR 60-90 ml/min calculated as by CKD-EPI • Hypertension should be controlled, i.e., =18 years and =25
Exclusion criteria
Exclusion criteria: Group 1 • Diagnosis of type 1 diabetes mellitus • Cardiovascular disease event in the last 6 months prior to enrollment as assessed by the investigator, including: myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, heart failure, transient ischemic attack (TIA) or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia. • Chronic use of sodium-glucose transporter-2 inhibitors, oral glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs), diuretics, or monoamine oxidase inhibitors. • Current urinary tract infection or active nephritis • History of allergy/hypersensitivity to any of the test agents • Contra-indication for MRI • Any other condition that prevents participation as judged by investigator. Group 2: Non-diabetic lean controls Exclusion criteria: • Macro-albuminuria (defined as UACR>30 mg/mmol) • . • Cardiovascular disease event in the last 6 months prior to enrollment as assessed by the investigator, including: myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, heart failure, transient ischemic attack (TIA) or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia. • Chronic use of renin-angiotensin-system blockers, sodium-glucose transporter-2 inhibitors, DPP-4 inhibitors, oral glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs), diuretics ormonoamine oxidase inhibitors. • Current urinary tract infection or active nephritis • History of allergy/hypersensitivity to any of the test agents • Contra-indication for MRI Group 3: T2DM controls with overweight and eGFR 60-90 ml/min Exclusion criteria: • Diagnosis of type 1 diabetes mellitus • Post-menopausal females (defined as no menses >1 year and follicle stimulating hormone (FSH) >31 U/L) • Cardiovascular disease event in the last 6 months prior to enrollment as assessed by the investigator, including: myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, heart failure, transient ischemic attack (TIA) or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia. • Chronic use of sodium-glucose transporter-2 inhibitors, oral glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs), diuretics, or monoamine oxidase inhibitors. • Current urinary tract infection or active nephritis • History of allergy/hypersensitivity to any of the test agents • Contra-indication for MRI • Any other condition that prevents participation as judged by investigator. Group 4: Non-diabetic controls with overweight and eGFR 60-90 ml/min • Post-menopausal females (defined as no menses >1 year and follicle stimulating hormone (FSH) >31 U/L) • Cardiovascular disease event in the last 6 months prior to enrollment as assessed by the investigator, including: myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, heart failure, transient ischemic attack (TIA) or significant cerebrovascular disease, unstable or previously u
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in kidney oxygenation in obese, hyperfiltering adults with T2D after bariatric surgery for men and women separately using BOLD-MRI | — |
Secondary
| Measure | Time frame |
|---|---|
| Main study parameters and endpoints: Kidney oxygenation: Oxygenation will be assessed by BOLD-MRI. Cortical and Medullary oxygenation will be assessed. Renal blood flow: Blood flow will be assessed by phase-contrast MRI. Kidney fat percentage: Fat percentage will be assessed by a 3-point Dixon MRI. Renal perfusion: Perfusion will be assessed by Arterial spin labeling (ASL). Kidney Renal hemodynamics, (i.e., GFR, ERPF) will be measured by the gold standard Iohexol and PAH clearance method based on timed urine sampling. In addition, renal perfusion will be assessed by use of phase-contrast MRI. Insulin sensitivity: will be measured by inducing a hyperinsulinemic-euglycemic clamp. Metabolic parameters: plasma concentrations of glucose, FFAs and lipids will be determined. Renal tubular function will be measured by 24-hour urine electrolyte excretions; markers of renal damage will include 24-hour urinary albumin excretion, albumin/creatinine ratio (UACR) and markers such as NGAL and KIM-1; Blood pressure and heart rate will be measured by using an automatic oscillometric device (Dinamap®); body anthropometrics; height, weight, BMI, waist/hip circumference, body water and fat percentage (by bioimpedance analysis); Additional urine and blood will be collected and appropriately stored for conditional determination of metabolic, biochemical and exploratory variables related to this project. VAT gene expression will be analyzed by RNA sequencing. | — |
Countries
Netherlands
Outcome results
None listed