acute effects of sglt2 inhibitor on kidney allograft oxygen tension

Conditions: Kidney Transplantation Recipients; Magnetic Resonance Imaging (MRI); Sodium-Glucose Transporter 2 Inhibitors; Non-Diabetic Patients; Randomized Controlled Trial; Placebo Control Design

Summary: the goal of this clinical trial is to investigate if a single dose of oral sglt2i, (50 mg jardiance) will change oxygen tension in the kidney transplant. the main questions it aims to answer are: * does a single dose of oral sglt2i (50 mg jardiance) change oxygen tension in the kidney transplant cortex and medulla, estimated by magnetic resonance imaging? * does a single dose of oral sglt2i (50 mg jardiance) change kidney transplant cortical and medullary perfusion? * does a single dose of oral sglt2i (50 mg jardiance) change kidney transplant artery blood flow? * does a single dose of oral sglt2i (50 mg jardiance) change blood glucoses, blood pressure and heart rate? researchers will compare a single dose of oral sglt2i (50 mg jardiance) to a placebo (a look-alike substance that contains no drug) to see if a single dose of oral sglt2i (50 mg jardiance) changes oxygen tension in the kidney transplant. kidney transplant recipients with out diabetes will: * meet for two intervention days. * a single dose of oral sglt2i (50 mg jardiance) or placebo will be given in random order, separated by at least 2 week washout period, the experiment will be repeated with the opposite treatment. * kidney cortex oxygenation, and blood flow in different compartments of the kidney transplant, is estimated by blood-oxygen-dependent level magnetic resonance imaging (bold-mri). patients are evaluated by routine clinical examination and routine biochemical measures for kidney transplant patients.

background: kidney transplantation is the best treatment of end-stage renal disease (esrd), although median allograft survival is only 15 years. in non-transplant diabetic and non-diabetic patient's sodium-glucose co-transporter type 2 inhibitors (sglt2i) protect kidney function, possibly by reducing the proximal tubule transport workload with subsequent improvement of renal oxygenation and relieve hypoxia. hypothesis: sglt2i in kidney transplant recipients (ktr) will improve kidney allograft cortex oxygenation. research objective: we aim to test the acute effect of sglt2i on kidney allograft oxygen tension. design: a randomized, double-blind, placebo-controlled, crossover intervention study. designed according to the consort statement methods: a single dose of oral sglt2i (50 mg jardiance) and placebo in random order, separated by at least 2 week washout period, the experiment will be repeated with the opposite treatment. kidney cortex oxygenation and blood flow in different compartments of the kidney allograft will be estimated by blood-oxygen-dependent level magnetic resonance imaging (bold-mri). patients will be evaluated by routine clinical examination and routine biochemical measures for transplant patients. primary endpoint: - kidney allograft cortical and medullary oxygen tension, estimated by bold-mri based renal t2\* relaxation rate. secondary endpoint: * renal cortical and medullary perfusion ml/100 g/min * renal artery blood flow ml/min * blood glucose mmol/l * systolic blood pressure (sysbp) and diastolic blood pressure (diabp) mmhg * heart rate (hr), beats min-1 study population: 8 non-diabetic kidney transplant recipients \> 6 months post-transplant and stable egfr \>20 ml/min will be recruited from odense university hospital (ouh) kidney transplant outpatient clinic.

Eligibility criteria:
inclusion criteria: * male or female patients, age ≥ 18 years. * non-diabetic kidney transplant recipients * \> 6 months post-transplant * stable egfr\> 20 ml/min (defined as egfr 20 ml/min ± 5 ml/min variation in the last 3 months) * immunosuppressive: tacrolimus (adport) and mycophenolatmofetil (myfenax/cellcept/mycophenolatmofetil) * capable of lying in a mr-scanner * capable of providing a signed informed consent and comply with study requirements. * negativ pregnancy test exclusion criteria: * diabetic kidney disease type 1 or 2 (world health organization (who) criteria) * hemoglobin a1c ≥ 48 mmol/mol * fasting venous plasma glucose ≥ 7,0 mmol/l or * 2-hours venous plasma glucose ≥ 11,1 mmol/l after oral glucose tolerance test (ogtt). * renal allograft failure (egfr\< 20 ml/min) * alanine aminotransferase (alat) \> 3 x upper normal limit * bilirubin \> 2 x upper normal limit * prednisone treatment * pregnancy * breastfeeding * exclusion criteria for mri o claustrophobia/physical not able to lie in mr-s

Keywords: sglt2i kidney transplant kidney transplant recipients mri magnetic resonance imaging bold-mri blood oxygen level dependent mri non-diabetic patients sodium-glucose transporter 2 inhibitors rct