Supported Research

Lay Abstract

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors were introduced in medical practice for the treatment of type 2 diabetes. Subsequently, they were found to protect against adverse cardiac events and progression of chronic kidney disease (CKD) to more advanced stages. Moreover, they were found to be effective and safe in patients without diabetes or in patients with moderate CKD. However, their efficacy is uncertain in patients with advanced kidney disease. In addition, these agents have not been studied in patients on hemodialysis (HD). This project includes two sub-studies that will explore the efficacy and safety of canagliflozin, an SGLT-2 inhibitor, among participants with advanced CKD, including those receiving HD. The first substudy will include 54 adult patients with advanced CKD. They will receive canagliflozin (one pill of 100 mg daily) for a total of 12 weeks (phase 1). Participants who have well tolerated this medication will then receive the higher dose of canagliflozin (one pill of 300 mg daily) for another 12 weeks (phase 2). At baseline and at the end of each study phase, excretion of proteins in the urine (a marker of kidney disease), concentration of the drug in the blood, and blood pressure will be measured. The second substudy will include 14 adult patients who are treated with chronic hemodialysis. They will also receive canagliflozin at the 100 and 300 mg dose for 12 weeks, respectively. The same endpoints will be assessed with the exception of protein excretion in the urine. Adverse events will be collected with both studies. This project will allow to assess the efficacy and safety of the lower and higher dose of this medication in patients with advanced CKD and HD. The study will provide important information with respect to use of these medications in patients with CKD who are at high risk of cardiac complications and have been excluded from research studies or who are not receiving optimal medical therapy.