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Effect of Empagliflozin on Kidney Biochemical and Imaging Outcomes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure with Reduced Ejection Fraction (SUGAR-DM-HF)

Matthew M.Y. Lee, Keith A. Gillis, Katriona J.M. Brooksbank, Sarah Allwood-Spiers, Pauline Hall Barrientos, Kirsty Wetherall, Giles Roditi, Bashair AlHummiany, Colin Berry, Ross T. Campbell, Victor Chong, Liz Coyle, Kieran F. Docherty, John G. Dreisbach, Bernd Kuehn, Catherine Labinjoh, Ninian N. Lang, Vera Lennie, Kenneth Mangion, Alex McConnachie, Clare L. Murphy, Colin J. Petrie, John R. Petrie, Kanishka Sharma, Steven Sourbron, Iain A. Speirits, Joyce Thompson, Paul Welsh, Rosemary Woodward, Ann Wright, Aleksandra Radjenovic, John J.V. McMurray, Pardeep S. Jhund, Mark C. Petrie, Naveed Sattar, Patrick B. Mark

In the SUGAR-DM-HF kidney study, led by Dr Matthew Lee with mentoring by Profs Naveed Sattar, Patrick Mark, and Mark Petrie from the School of Cardiovascular & Metabolic Health at the University of Glasgow, the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin reduced kidney perfusion and reduced kidney apparent extracellular volume, both measured by MRI, in patients with heart failure.

Reduction in kidney perfusion and congestion may be mechanisms by which SGLT2 inhibitors affect kidney function in heart failure. These results have been presented at the American Society of Nephrology (ASN) Kidney Week 2021 as a late-breaking clinical trial, and recently published in the journal Circulation in July 2022.

Prespecified outcomes included change from baseline to 36 weeks in kidney MRI biomarkers (kidney perfusion measured by both arterial spin labeling [ASL] and magnetic resonance renography [MRR], kidney pre-contrast longitudinal relaxation time [T1], kidney apparent extracellular volume [aECV; post-contrast T1] and total kidney volume) and soluble biomarkers (estimated glomerular filtration rate Chronic Kidney Disease Epidemiology Collaboration creatinine, urinary albumin creatinine ratio, urinary sodium concentration, fractional excretion of sodium, and urinary potassium concentration).

Integrated gadolinium contrast-enhanced cardio-kidney MRI (MAGNETOM Prisma 3T scanner, Siemens) was performed at baseline and week 36. Reproducibility kidney MRI analyses are published elsewhere. Where both kidneys could not be aligned within the same coronal oblique view, the right kidney was prioritized. For ASL, T1, and aECV, regions of interest were drawn manually around the whole kidney, cortex, and an area of user-defined representative cortex. For MRR and kidney volumes, regions of interest were drawn around the whole kidney. Observers were blinded to subject identification, scan date, clinical data, and randomization arm. The primary results analyses excluded patients in atrial fibrillation/flutter at week 36 to avoid cardiac image degradation. For kidney analyses, we included patients in atrial fibrillation/flutter at week 36.

Link to Paper

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First published: 31 August 2022