CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients

CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients

CREST-KT is a single-center, double-blinded, randomized trial of empagliflozin therapy in 72 kidney transplant recipients with (n=36) and without type 2 diabetes (n=36). After evenly dividing patients by type 2 diabetes diagnosis, patients will be randomized 2:1 to empagliflozin 10mg versus placebo.

A screening visit will occur at which time an informed consent will be obtained, and eligibility determined. Women of childbearing potential will have a serum pregnancy test performed. This will be followed by a baseline visit. A renal biopsy and a 3D echocardiogram will be performed. At the next visit randomization will be performed and the subjects will receive their study medication, either empagliflozin or a placebo. Following the randomization visit the subject will return every 3 months (visits 2-7) for a total of 6 visits spanning 18 months. At each visit vital signs and weight will be taken. Other procedures include labs drawn for hematology, basic chemistry, coagulation, Glycated hemoglobin and serum insulin. A 3 D echocardiogram is repeated on Visits 4 and 6. A renal biopsy is repeated on Visit 3.

Inclusion Criteria:

1. Equal to or greater than 12 months and up tp 60 months post kidney transplant
2. Estimated glomerular filtration rate (eGFR) equal to or greater than 30ml/min/1.73m squared at screening
3. Standard immunosuppression, including calcineurin inhibitor, Mycophenolate Mofetil or Sodium and a glucocorticoid
4. Able to provide written consent -

Exclusion Criteria:

1. Type I diabetes
2. Any other solid organ transplant
3. Hemoglobin A1c greater than 12 %
4. SGLT2i use at the time of enrollment
5. Prior SGLT2i allergy or intolerance
6. Pregnant or nursing at the time of enrollment
7. History of antibody medicated rejection (AMR) or a Banff score greater than 2B for acute cellular rejection (ACR)
8. Active anticoagulant use other than aspirin 81 mg for primary prevention of cardiovascular disease
9. Known positive donor-specific antibodies prior to enrollment
10. Uncircumcised men
11. Greater than 2 urinary tract infections (UTI) over the 12 months prior to enrollment
12. Any genital infections over the 12 months prior to enrollment -