Molecular Mechanisms of SGLT2 Inhibition in Diabetic Kidney Disease
The goal of this open-label, non-randomized clinical trial is to determine what effects, if any, an FDA-approved drug class known as SGLT2 inhibitors (Canagliflozin or INVOKANA) has any protective effects on kidney function in Type 2 diabetes. We are looking for participants 18-80 years of age, who have had a clinical diagnosis of Type 2 diabetes for ≥ 3 years. Participants will be asked to sign a consent and complete a screening visit prior to study entry including the following procedures for this study: Consent and Screening: * Laboratory tests to determine baseline health * Ultrasound to measure kidney size and ensure presence of 2 functioning kidneys Month 0: * Study entry kidney MRI (day 0) * Study entry kidney biopsy (within 30 days of MRI) * Study entry visit for dispensing 100 mg/daily Canagliflozin medication 3 month supply Month 3: * Study visit to dispense remaining 3 months of 100 mg/daily Canagliflozin medication * Review of systems Month 6: * Follow-up kidney MRI * Follow-up kidney biopsy Study participants will also be requested to provide blood and urine samples for biobanking purposes. They will also be provided the opportunity to provide a stool sample at two time points, as well as the option to participate in a related study collecting samples to create induced Pluripotent Stem Cells (iPSCs). Participants will be compensated for their time and loss of work time, additionally, a nominal additional compensation for optional stool and iPSC samples.
• Aged 18-80 years.
⁃ The lower age limit was set so renal function test results would not reflect changes associated with growth.
• Diagnosis of type 2 diabetes for ≥ 3 years.
• Estimated GFR \>45 and \< 90 ml/min/1.73m2 as determined from the CKD-EPI equation using serum creatinine (Levey et al., 2009)
• A screening urinary albumin-to-creatinine ratio \<3000 mg/g.
• Willingness to participate after receiving a thorough explanation of the study.
• Participants receiving a RAAS inhibitor must have been receiving the drug at maximum tolerable dose for at least 3 months prior to the study baseline examination.
• Participants receiving a GLP-1 receptor agonist must have been receiving the drug for at least 3 months prior to the study baseline examination.
• Participants must meet the current clinical guidelines for prescribing SGLT2 inhibitors, to maintain FDA-approved standards