Empagliflozin and salt restriction in people with type 2 diabetes and chronic kidney disease

INTERVENTION: Empagliflozin 10 mg once daily oral tablet for 4 weeks combined with sodium restriction for 4 weeks. Participants will be randomised to start with empagliflozin combined with sodium restriction for 4 weeks or empagliflozin combined with their usual sodium intake for 4 weeks. Participants will then undergo a 2‐week washout period and crossover to the alternative sodium intervention (usual sodium intake or sodium restriction) combined with empagliflozin for 4 weeks. Adherence to taking empagliflozin will be monitored with the use of a participant study diary to record the administration of each empagliflozin tablet. A Dietician with minimum 3 years experience will provide education to participants individually regarding sodium restriction over the internet or via telephone call. Participants can receive this virtual education at their homes. The Dietician will provide an initial education session (approximately 1‐2 hours) at the time of randomisation to sodium restriction (in the week prior to starting empagliflozin treatment) and then have a follow‐up session (approximately 30 minutes ‐ 1 hour) 1‐2 weeks after the initial individual education and after starting empagliflozin treatment. Information provided to participants at the initial education session will include discussion of foods high in sodium and how to substitute high sodium foods for foods lower in sodium during the sodium restriction period. At the follow‐up session the Dietician will discuss the participant s progress with a sodium‐restricted diet. The participant will be asked to follow a sodium‐restricted diet for 4 weeks. Changes to sodium intake will be monitored with a participant food diary. CONDITION: Metabolic and Endocrine ‐ Diabetes Renal and Urogenital ‐ Kidney disease Type 2 diabetes;Chronic kidney disease; ; Type 2 diabetes ; Chronic kidney disease PRIMARY OUTCOME: Change in 24‐hour ambulatory blood pressure using a 24‐hour ambulatory blood pressure device[Baseline, 4 weeks after intervention commencement] INCLUSION CRITERIA: ‐ Age range: 18 ‐ 75 years ‐ Diagnosis of type 2 diabetes and HbA1c up to 10% ‐ Stage 2, 3 or 4 CKD (eGFR 60‐89 mL/min/1.73 m2 and urine albumin‐to‐creatinine ratio >30 mg/g, eGFR 30‐59 mL/min/1.73m2 or 15 – 29 mL/min/1.73m2, respectively) at the time of screening, and stable renal function defined as a difference of <30% between two consecutive eGFR in the 3 months before the screening visit ‐ On stable anti‐hypertensive dose of an angiotensin‐converting‐enzyme (ACE) inhibitor or angiotensin‐receptor blocker (ARB) in the one month before the screening visit ‐ Willing to give written informed consent and willingness to participate to and comply with the study SECONDARY OUTCOME: Change in estimated glomerular filtration rate (eGFR) measured using a peripheral blood sample[Baseline, 2 and 4 weeks after intervention commencement, 2 weeks after intervention cessation] Change in extracellular fluid volume estimated by bioimpedance spectroscopy (measured using ImpediMed SFB7 device)[Baseline, 4 weeks after intervention commencement] Change in fractitional endogenous lithium excretion ‐ measured using a peripheral blood and urine sample[Baseline, 4 weeks after intervention commencement] Change in haematocrit measured using a peripheral blood sample[Baseline, 2 weeks and 4 weeks after intervention commencement, 2 weeks after intervention cessation] Change in intracellular fluid volume estimated by bioimpedance spectroscopy (measured using ImpediMed SFB7 device)[Baseline, 4 weeks after intervention commencement] Change in serum creatinine [Baseline, 2 and 4 weeks after intervention commencement, 2 weeks after intervention cessation] Change in serum fasting beta‐hydroxybutyrate measured using a peripheral blood sample[Baseline, 2 and 4 weeks after intervention commencement, 2 weeks after intervention cessation] Change in serum fructosamine[Baseline, 4 weeks after intervention commencement] Change in serum phosphate[Baseline, 4 weeks after intervention commencement, 2 weeks after intervention cessation] Change in serum uric acid[Baseline, 2 and 4 weeks after intervention commencement, 2 weeks after intervention cessation] Change in total body water estimated by bioimpedance spectroscopy (measured using ImpediMed SFB7 device)[Baseline, 4 weeks after intervention commencement] Change in urine albumin‐to‐creatinine ratio (24‐hour collection)[Baseline, 4 weeks after intervention commencement] Empagliflozin concentration in plasma[Baseline, 4 weeks after intervention commencement]