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
  • , Renal Lifecycle Trial Cardiac Imaging Sub-studies Investigators
  • , 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*
*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article numbersfaf376
JournalClinical Kidney Journal
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 2026

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

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