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

Micky Karsten; Sunil V Badve; Ron T Gansevoort; Stefan P Berger; Hiddo J L Heerspink; Alferso C Abrahams; Laurent Billot; Rianne H A C M Bon; Mariëlle A C J Gelens; Dean Guinness; Christian Hamilton-Craig; Loek van Heerebeek; Marc H Hemmelder; Lauren Houston; Rebecca Kozor; Dirk R J Kuypers; Helen Monaghan; Bruce Neal; Brendon L Neuen; James Otton; Vlado Perkovic; Adil Rajwani; Angela Y Wang; Marc G Vervloet; Clare Arnott; Lily Jakulj; Renal Lifecycle Trial Cardiac Imaging Sub-studies Investigators

doi:10.1093/ckj/sfaf376

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

Clin Kidney J. 2025 Dec 2;19(1):sfaf376. doi: 10.1093/ckj/sfaf376. eCollection 2026 Jan.

Authors

Micky Karsten^{1

2}, Sunil V Badve^{3

4}, Ron T Gansevoort⁵, Stefan P Berger⁶, Hiddo J L Heerspink⁷, Alferso C Abrahams⁸, Laurent Billot³, Rianne H A C M Bon⁹, Mariëlle A C J Gelens¹⁰, Dean Guinness¹¹, Christian Hamilton-Craig¹², Loek van Heerebeek¹³, Marc H Hemmelder¹⁴, Lauren Houston^{3

15}, Rebecca Kozor^{16

17}, Dirk R J Kuypers¹⁸, Helen Monaghan^{3

19}, Bruce Neal³, Brendon L Neuen^{3

20}, James Otton¹⁹, Vlado Perkovic¹⁹, Adil Rajwani²¹, Angela Y Wang²², Marc G Vervloet²³, Clare Arnott³, Lily Jakulj^{1

2

24}; Renal Lifecycle Trial Cardiac Imaging Sub-studies Investigators

Collaborators

Renal Lifecycle Trial Cardiac Imaging Sub-studies Investigators:
Ronald van Etten, Karlien Francois, Pedro Gois, Joost van der Heijden, Jane Holt, Shilpa Jesudason, Karen Keung, Yu Sok Kim, Rathika Krishnasamy, Hemant Kulkarni, Joep van der Leeuw, Angela Makris, Rosemary Masterson, Amanda Mather, Gurbey Ocak, Dharmenaan Palamuthusingam, Eugenia Pedagogos, Carl Siegert, Brendan Smyth, Vikas Srivastava, Girish Talaulikar, Rowena Vleut, Femke Waanders, Germaine Wong, Muh Geot Wong, Kate Wyburn

Affiliations

¹ Department of Nephrology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
² Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, Amsterdam, The Netherlands.
³ The George Institute for Global Health, University of New South Wales, Sydney, Australia.
⁴ Department of Renal Medicine, St George Hospital, Sydney, Australia.
⁵ Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁶ Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁷ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁸ Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
⁹ Department of Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
¹⁰ Division of Nephrology, Department Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
¹¹ Kidney Health Consumer Panel, The George Institute of Global Health, University of New South Wales, Sydney, Australia.
¹² The University of Queensland, Faculty of Medicine and Centre for Advanced Imaging, Brisbane, Australia.
¹³ Department of Cardiology, OLVG, Amsterdam, The Netherlands.
¹⁴ Department of Internal Medicine, division of Nephrology, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁵ Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.
¹⁶ The University of Sydney, Sydney, Australia.
¹⁷ Department of Cardiology, Royal North Shore Hospital, Sydney, Australia.
¹⁸ Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
¹⁹ University of New South Wales, Sydney, Australia.
²⁰ Department of Renal Medicine, Royal North Shore Hospital, Sydney, Australia.
²¹ Royal Perth Hospital, Department of Cardiology, Perth, Australia.
²² Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore.
²³ Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
²⁴ Dianet Dialysis Center, Amsterdam, The Netherlands.

Abstract

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.

Keywords: cardiac magnetic resonance imaging; chronic kidney disease; dapagliflozin; echocardiography; sodium-glucose co-transporter 2 inhibitors.

Associated data

ClinicalTrials.gov/NCT05374291