Acute Effects of GLP-1 on Renal Hemodynamics

Study Overview
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Brief Summary
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This study investigates the hypothesis, that GLP-1's suppression of ANG II and natriuretic action increase medullary perfusion and decrease oxygen consumption, leading to higher tissue oxygenation.

Detailed Description
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Human studies have recently demonstrated a significant natriuretic effect of GLP-1 when the extracellular fluid volume (ECFV) is expanded by intravenous sodium-loading; in these studies, there was a suppression of ANG II with no change in net renal hemodynamics, pointing to a tubular mechanism for reduced NaCl reabsorption secondary to the ANG II suppression. In the current randomized and controlled study, investigators aim to test the hypothesis that GLP-1's suppression of ANG II and natriuretic action increase medullary perfusion and decrease oxygen consumption, leading to higher tissue oxygenation. Thus, contributing to the renoprotective action of GLP-1. Under fixed sodium intake for 4 days before each study day, 10 healthy male participants will be investigated during a 1-hour infusion of GLP-1 (1.5 pmol/kg/min) or vehicle together with an intravenous infusion of 0.9% NaCl. Interleaved measurements of RAF, oxygenation (T2*) and perfusion by arterial spin labeling in the renal cortex and medulla at fixed time points will be conducted, using Magnetic Resonance Imaging (MRI).

Official Title
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Acute Effects of GLP-1 on Renal Hemodynamics: Simultaneous Perfusion and Oxygenation Measurements in Cortex and Medulla Using Magnetic Resonance Imaging

Conditions
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The GLP-1-mediated Gut-kidney Axis

Intervention / Treatment
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* Drug: Glucagon-Like Peptide 1
* Drug: saline 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal health demonstrated by medical examination. Normal values for fasting plasma glucose, total cholesterol, triglyceride, HDL, LDL, creatinine, AST, ALT and electrolyte concentrations. Exclusion Criteria: Immunosuppressive treatment for the previous 12 months. Alcohol abuse. Medical treatment with oral glucocorticoids, dipeptidyl peptidase-4 (DPP-4) inhibitors, or GLP-1 receptor agonists that, in the opinion of the investigator, may interfere with glucose metabolism. Use of lithium. Medical treatment that affects insulin secretion or cardiovascular efficacy goals. Liver disease (ALT> 2 x normal value). Renal impairment (creatinine> 130 µM and / or albuminuria). Severe claustrophobia. MRI incompatible foreign bodies.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: human glucagon-like peptide-1<br>Intervention: Drug: human glucagon-like peptide-1 Other names: GLP-1 | Drug: Glucagon-Like Peptide 1<br>* Intravenous infusion (1.5 pmol/kg/min) for 60 min.<br>* Other names: GLP-1;|
| Placebo Comparator: Placebo<br>Intervention: Drug: Placebo (saline) Other names: Placebo for human glucagon-like peptide-1 | Drug: saline 0.9%<br>* Intravenous infusion for 60 min.<br>* Other names: Placebo for GLP-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T2* signal | Changes in T2* signal in renal cortex and medulla | 1 hour | 
| Arterial Spin Labeled (ASL) | Changes in Arterial Spin Labeled (ASL) MRI Perfusion Imaging in renal cortex and medulla | 1 hour | 
| Renal Artery Flow Phase (RAF) | Changes in Renal Artery Flow Phase (RAF)-Contrast Magnetic Resonance | 1 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney, glucagon-like peptide-1, renal hemodynamics, renal blood flow