Cardiac impact of dapagliflozin in advanced chronic kidney disease: rationale and design of the Renal Lifecycle Trial cardiac imaging sub-studies.

Background: Patients with chronic kidney disease (CKD) are frequently hospitalized for heart failure. Sodium-glucose co-transporter 2 (SGLT2)-inhibitors improve cardiorenal outcomes in CKD and heart failure, at least in estimated glomerular filtration rate (eGFR) ranges 20-60 ml/min/1.73 m2, possibly through direct cardiac effects. In the cardiac imaging sub-studies of the Renal Lifecycle Trial, we aim to establish the effects of SGLT2-inhibition on cardiac structure and function in patients with advanced CKD, kidney failure and in kidney transplant recipients. Methods: In the Renal Lifecycle Trial, patients with advanced CKD (eGFR ≤25 ml/min/1.73 m2), those treated with hemodialysis or peritoneal dialysis (PD) or kidney transplant recipients (eGFR ≤45 ml/min/1.73 m2), are randomized to receive either dapagliflozin or placebo. The echocardiography sub-study (acronym: STOP-HF-in-PD) will enroll 100 PD-treated patients, who undergo echocardiography at baseline, and at 6 and 12 months post-randomization. In the cardiac magnetic resonance imaging (MRI) sub-study, 250 Renal Lifecycle Trial participants across all three groups (i.e. advanced CKD, dialysis, kidney transplant recipients), including a subset of STOP-HF-in-PD participants, will undergo cardiac MRI at baseline, and at 12 months post-randomization. The primary endpoint of STOP-HF-in-PD is the difference in left ventricular global longitudinal strain, a measure of cardiac function, after 6-months of dapagliflozin compared to placebo. For the cardiac MRI sub-study, the primary endpoint is the difference of indexed left ventricular mass after 12 months of dapagliflozin compared to placebo. Conclusions: The Renal Lifecycle Trial cardiac imaging sub-studies will generate novel data on the effects of SGLT2-inhibition on cardiac structure and function in a population with advanced CKD, in whom SGLT2-inhibitor induced cardiovascular protection remains to be established. Clinical Trial Registration: The Renal Lifecycle Trial and its sub-studies are registered at ClinicalTrials.gov under registration number NCT05374291.