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)
2022; Lippincott Williams & Wilkins; Volume: 146; Issue: 4 Linguagem: Inglês
10.1161/circulationaha.122.059851
ISSN1524-4539
AutoresMatthew M.Y. Lee, Keith Gillis, Katriona 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 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,
Tópico(s)Chronic Kidney Disease and Diabetes
ResumoHomeCirculationVol. 146, No. 4Effect 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) Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBEffect 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, PhD, Keith A. Gillis, PhD, Katriona J.M. Brooksbank, PhD, Sarah Allwood-Spiers, PhD, Pauline Hall Barrientos, PhD, Kirsty Wetherall, BSc, Giles Roditi, MBChB, Bashair AlHummiany, MSc, Colin Berry, PhD, Ross T. Campbell, PhD, Victor Chong, MD, Liz Coyle, Kieran F. Docherty, MBChB, John G. Dreisbach, MBChB, Bernd Kuehn, PhD, Catherine Labinjoh, MD, Ninian N. Lang, MBChB, PhD, Vera Lennie, MD, Kenneth Mangion, PhD, Alex McConnachie, PhD, Clare L. Murphy, MBChB, Colin J. Petrie, PhD, John R. Petrie, MD, PhD, Kanishka Sharma, PhD, Steven Sourbron, PhD, Iain A. Speirits, MSc, Joyce Thompson, RN, Paul Welsh, PhD, Rosemary Woodward, BSc, Ann Wright, BSc, Aleksandra Radjenovic, PhD, John J.V. McMurray, MD, Pardeep S. Jhund, PhD, Mark C. Petrie, MBChB, Naveed Sattar, MD, PhD and Patrick B. Mark, PhD Matthew M.Y. LeeMatthew M.Y. Lee https://orcid.org/0000-0001-9213-2067 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Glasgow Royal Infirmary, UK (M.M.Y.L., G.R., J.R.P., M.C.P., N.S.). Search for more papers by this author , Keith A. GillisKeith A. Gillis Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , Katriona J.M. BrooksbankKatriona J.M. Brooksbank Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , Sarah Allwood-SpiersSarah Allwood-Spiers Department of Clinical Physics and Bioengineering, NHS Greater Glasgow and Clyde, UK (S.A.-S., P.H.B.). Search for more papers by this author , Pauline Hall BarrientosPauline Hall Barrientos Department of Clinical Physics and Bioengineering, NHS Greater Glasgow and Clyde, UK (S.A.-S., P.H.B.). Search for more papers by this author , Kirsty WetherallKirsty Wetherall Robertson Centre for Biostatistics (K.W., A.M.), University of Glasgow, UK. Search for more papers by this author , Giles RoditiGiles Roditi Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Glasgow Royal Infirmary, UK (M.M.Y.L., G.R., J.R.P., M.C.P., N.S.). Search for more papers by this author , Bashair AlHummianyBashair AlHummiany University of Leeds, UK (B.A., S.S.). University of Leeds, UK (B.A., S.S.). Search for more papers by this author , Colin BerryColin Berry https://orcid.org/0000-0002-4547-8636 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , Ross T. CampbellRoss T. Campbell Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , Victor ChongVictor Chong University Hospital Crosshouse, Kilmarnock, UK (V.C.). Search for more papers by this author , Liz CoyleLiz Coyle Search for more papers by this author , Kieran F. DochertyKieran F. Docherty https://orcid.org/0000-0002-5446-9969 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , John G. DreisbachJohn G. Dreisbach https://orcid.org/0000-0001-8702-4520 Golden Jubilee National Hospital, Glasgow, UK (J.G.D., M.C.P.). Search for more papers by this author , Bernd KuehnBernd Kuehn Siemens Healthcare GmbH, Erlangen, Germany (B.K.). Search for more papers by this author , Catherine LabinjohCatherine Labinjoh Forth Valley Royal Hospital, Larbert, UK (C.L.). Search for more papers by this author , Ninian N. LangNinian N. Lang https://orcid.org/0000-0001-8441-6887 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , Vera LennieVera Lennie University Hospital Ayr, UK (V.L.). Aberdeen Royal Infirmary, UK (V.L.). Search for more papers by this author , Kenneth MangionKenneth Mangion https://orcid.org/0000-0002-3505-7440 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , Alex McConnachieAlex McConnachie https://orcid.org/0000-0002-7262-7000 Robertson Centre for Biostatistics (K.W., A.M.), University of Glasgow, UK. Search for more papers by this author , Clare L. MurphyClare L. Murphy Royal Alexandra Hospital, Paisley, UK (C.L.M.). Search for more papers by this author , Colin J. PetrieColin J. Petrie Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. University Hospital Monklands, Airdrie, UK (C.J.P.). Search for more papers by this author , John R. PetrieJohn R. Petrie https://orcid.org/0000-0002-4894-9819 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Glasgow Royal Infirmary, UK (M.M.Y.L., G.R., J.R.P., M.C.P., N.S.). Search for more papers by this author , Kanishka SharmaKanishka Sharma University of Sheffield, UK (K.S., S.S.). Search for more papers by this author , Steven SourbronSteven Sourbron University of Sheffield, UK (K.S., S.S.). University of Leeds, UK (B.A., S.S.). Search for more papers by this author , Iain A. SpeiritsIain A. Speirits West Glasgow Ambulatory Care Hospital, UK (I.A.S.). Search for more papers by this author , Joyce ThompsonJoyce Thompson Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , Paul WelshPaul Welsh https://orcid.org/0000-0002-7970-3643 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Search for more papers by this author , Rosemary WoodwardRosemary Woodward Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , Ann WrightAnn Wright Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , Aleksandra RadjenovicAleksandra Radjenovic Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Search for more papers by this author , John J.V. McMurrayJohn J.V. McMurray https://orcid.org/0000-0002-6317-3975 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , Pardeep S. JhundPardeep S. Jhund https://orcid.org/0000-0003-4306-5317 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). Search for more papers by this author , Mark C. PetrieMark C. Petrie https://orcid.org/0000-0002-6333-9496 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Glasgow Royal Infirmary, UK (M.M.Y.L., G.R., J.R.P., M.C.P., N.S.). University Hospital Crosshouse, Kilmarnock, UK (V.C.). *M. C. Petrie, N. Sattar, and P. B. Mark contributed equally. Search for more papers by this author , Naveed SattarNaveed Sattar https://orcid.org/0000-0002-1604-2593 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Glasgow Royal Infirmary, UK (M.M.Y.L., G.R., J.R.P., M.C.P., N.S.). *M. C. Petrie, N. Sattar, and P. B. Mark contributed equally. Search for more papers by this author and Patrick B. MarkPatrick B. Mark Correspondence to: Patrick B, Mark, PhD, British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, 126 University Place, University of Glasgow, Glasgow, G12 8TA United Kingdom. Email E-mail Address: [email protected] https://orcid.org/0000-0003-3387-2123 Institute of Cardiovascular and Medical Sciences (M.M.Y.L., K.A.G., K.J.M.B., G.R., C.B., R.T.C., L.C., K.F.D., N.N.L., K.M., C.J.P., J.R.P., P.W., A.W., A.R., J.J.V.M., P.S.J., M.C.P., N.S., P.B.M.), University of Glasgow, UK. Queen Elizabeth University Hospital, Glasgow, UK (M.M.Y.L., K.A.G., G.R., C.B., R.T.C., K.F.D., N.N.L., K.M., J.T., R.W., A.W., J.J.V.M., P.S.J., P.B.M.). *M. C. Petrie, N. Sattar, and P. B. Mark contributed equally. Search for more papers by this author Originally published25 Jul 2022https://doi.org/10.1161/CIRCULATIONAHA.122.059851Circulation. 2022;146:364–367Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of worsening kidney function in patients with heart failure and reduced ejection fraction (HFrEF).1 Comparatively little is known about the effects of these drugs on kidney perfusion in the setting of randomized controlled trials. We studied effects of these drugs using kidney magnetic resonance imaging (MRI).We conducted a randomized, double-blind, placebo-controlled trial investigating the effects of empagliflozin in patients with New York Heart Association functional class II to IV, left ventricular ejection fraction ≤40%, and type 2 diabetes or prediabetes. Patients were randomly assigned 1:1 to empagliflozin 10 mg daily or placebo. The study design, screening, consent process, ethical approvals, and main results are published.2 The study had ethical committee approval, and all participants gave written informed consent. Data may be available on request.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.3 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.2 For kidney analyses, we included patients in atrial fibrillation/flutter at week 36.One hundred five patients were randomly assigned: mean age, 68.7 (SD 11.1) years; 77 (73.3%) male; 82 (78.1%) diabetes and 23 (21.9%) prediabetes; mean left ventricular ejection fraction 32.5% [9.8%]; mean estimated glomerular filtration rate Chronic Kidney Disease Epidemiology Collaboration creatinine 67.6 [22.1] mL/min/1.73m2; and median urinary albumin creatinine ratio 11 (interquartile range, 2–45) mg/g. Of 52 patients randomly assigned to empagliflozin, 45 remained on randomized therapy and underwent baseline and 36-week MRI.2 Of 53 patients randomly assigned to placebo, 50 remained on randomized therapy and underwent baseline and 36-week MRI.Compared with placebo, empagliflozin reduced right whole kidney perfusion (ASL) by 25 (95% CI, –47 to –4; P=0.021) mL/100mL/min (Figure), reduced right whole kidney aECV by 4.8 (–8.8 to –0.8; P=0.020) %, and reduced urinary sodium concentration by 14 (–25 to –3; P=0.012) mmol/L. Similar results were seen for right cortex, left whole kidney, left cortex kidney perfusion (ASL), and left whole kidney aECV. There were no between-group differences in MRR (although directionally concordant), kidney T1 (right whole kidney), total kidney volume, estimated glomerular filtration rate Chronic Kidney Disease Epidemiology Collaboration creatinine, urinary albumin creatinine ratio, fractional excretion of sodium, or urinary potassium concentration at 36 weeks.Download figureDownload PowerPointFigure. Change in kidney perfusion (ASL, MRR) and aECV from baseline to week 36. Data are presented as mean and error bars represent 95% CIs. Treatment effect was calculated using an analysis of covariance model adjusted for treatment group, age at baseline, diabetes status, and baseline value. aECV indicates apparent extracellular volume; ASL, arterial spin labelling; MRI, magnetic resonance imaging; and MRR, magnetic resonance renography.Within each randomization group compared with baseline, for empagliflozin, ASL was unchanged: right whole kidney (P=0.55), left whole kidney (P=0.45), right cortex (P=0.69), and left cortex (P=0.33). With placebo, ASL was unchanged in the right whole kidney (P=0.059), left whole kidney (P=0.07), and left cortex (P=0.14), but increased in the right cortex (P=0.038). In the empagliflozin group, right kidney (P=0.0094) and both kidneys (P=0.013) MRR decreased but not left kidney MRR (P=0.058). In the placebo group, right kidney (P=0.24), left kidney (P=0.33), and both kidneys (P=0.25) MRR were unchanged.ASL was unchanged in the empagliflozin group. ASL of the right cortex increased in the placebo group, which is an unexpected, possibly chance finding. The placebo-corrected finding of ASL reduction with empagliflozin compared with placebo is hypothesis generating. There were directionally concordant changes in kidney perfusion by MRR. These changes suggest possible protective effects against glomerular hyperfiltration with reduction in ASL as a surrogate of intraglomerular perfusion. Sustained reduction seen in kidney perfusion (ASL) over 36 weeks is consistent with trajectories of kidney function observed in SGLT2 inhibitor outcome trials in HFrEF, with estimated glomerular filtration rate in the SGLT2 inhibitor group initially lower than in the placebo group until 76 weeks (EMPEROR-Reduced [Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction]) and 86 weeks (DAPA-HF [Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure]).4,5 Empagliflozin reduced kidney aECV, which we speculate represents kidney decongestion by reduction in renal interstitial fluid.We know of few other trials examining the effects of SGLT2 inhibition on kidney mechanisms in heart failure; these trials (NCT03027960, NCT03226457, and NCT03198585) had shorter follow-up duration of 2, 6, and 12 weeks, respectively. To our knowledge, this is the first kidney MRI trial using SGLT2 inhibition in HFrEF. Other trials assess SGLT2 inhibition with kidney MRI, although these trials are in patients without heart failure (NCT03093103, NCT04193566, and ChiCTR2000037951).Empagliflozin reduced kidney perfusion measured by ASL, with directionally concordant changes in MRR, and reduced aECV in patients with HFrEF and type 2 diabetes or prediabetes. Reduction in kidney perfusion and congestion may be mechanisms by which SGLT2 inhibitors affect kidney function in HFrEF.Article InformationRegistration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03485092.Sources of FundingThis trial was supported by an investigator-initiated study grant from Boehringer Ingelheim. Boehringer Ingelheim has provided support in terms of funding and investigational medicinal product (IMP). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation or decision to submit the manuscript for publication. Drs Gillis, Roditi, and Mark hold a grant for studying clinical use of renal MRI imaging funded by Kidney Research UK (KS_IN_002_20180913). Drs Berry, McMurray, Dr M.C. Petrie, and Sattar are supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217). Dr Berry has received research support from the British Heart Foundation (PG/17/2532884, FS/17/26/32744, and RE/18/6134217) and the Medical Research Council (MR/S005714/1). Dr Mangion was supported by a British Heart Foundation Clinical Training Fellowship (FS/15/54/31639). Dr Sourbron was supported by the Innovative Medicines Initiative 2 Joint Undertaking (No. 115974, BEAt-DKD) and the Medical Research Council (MR/P023398/1, HEPARIM study [Hepatectomy Risk Assessment With Functional Magnetic Resonance Imaging]).Nonstandard Abbreviations and AcronymsaECVapparent extracellular volumeASLarterial spin labelingHFrEFheart failure and reduced ejection fractionMRImagnetic resonance imagingMRRmagnetic resonance renographySGLT2Sodium-glucose cotransporter 2Disclosures Dr Lee’s employer, the University of Glasgow, has received grant support from Boehringer Ingelheim. Dr Gillis reports personal fees from Napp, AstraZeneca, and Vifor. Dr Berry is employed by the University of Glasgow, which holds consultancy and research agreements with companies that have commercial interests in the diagnosis and treatment of ischemic heart disease, including Abbott Vascular, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, HeartFlow, Menarini Farmaceutica, Opsens, Philips, and Siemens Healthcare. Dr Docherty’s employer, the University of Glasgow, is paid by AstraZeneca for involvement in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure). Dr Kuehn is an employee of Siemens Healthcare GmbH. Dr Lang has received consultancy fees from AstraZeneca and Pharmacosmos and speaker’s fees from Roche, Pfizer, and Novartis. He receives grant support from Roche Diagnostics (paid to his employer, the University of Glasgow). Dr J.R. Petrie has received research grants from the Juvenile Diabetes Research Foundation. He has also received personal fees and travel support from Novo Nordisk and Merck KGaA (Germany), personal fees from Abbott, ACI Clinical, Biocon, and IQVIA, and nonfinancial support from AstraZeneca, Dexcom, Merck KGaA (Germany), and Itamar Medical. Dr Sourbron reports research funding from European Federation of Pharmaceutical Industries and Associations (EFPIA) through the Innovative Medicines Initiative, and from Bayer AG, GlaxoSmithKline and General Electric for co-funded PhD studentships. Mr Speirits reports speaker fees from AstraZeneca, BMS-Pfizer, Daiichi-Sankyo, Novartis, and Servier, and advisory board fees from Boehringer Ingelheim. Dr Welsh reports grant income from Roche Diagnostics, AstraZeneca, and Novartis, and speaker fees from Novo Nordisk, outside the submitted work. Dr McMurray’s employer, the University of Glasgow, has been paid by AbbVie, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, DalCor, GSK, Merck Sharp & Dohme, Novartis, Resverlogix, and Theracos for his participation in clinical trials and by Alnylam, AstraZeneca, Cardurion, Novartis, and Pfizer for consultancy, advisory board membership, or lectures. Dr Jhund’s employer, the University of Glasgow, is paid by AstraZeneca for involvement in the DAPA-HF and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials. He has also received consulting, advisory board, and speaker’s fees from Novartis and AstraZeneca, advisory board fees from Cytokinetics, and a grant from Boehringer Ingelheim. Dr M.C. Petrie has received research grants or consultancy fees from SQ Innovations, AstraZeneca, Roche, Boehringer Ingelheim, Pharmacosmos, Eli Lilly, Napp Pharmaceuticals, Novartis, and Novo Nordisk and has served on clinical events committees for AbbVie, Alnylam, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Resverlogix, and Novo Nordisk. Dr Sattar has consulted for or received lecture fees from Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi. He has received grant support from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics through his institution, the University of Glasgow. Dr Mark reports research funding from Boehringer Ingelheim, paid advisory boards and lecture fees from AstraZeneca, Astellas, Napp, Vifor-Fresenius, Novartis, Pharmacosmos and travel support from Pharmacosmos, Napp and Vifor. University of Glasgow and National Health Service Greater Glasgow and Clyde Trust have a master research agreement with Siemens Healthcare to use the renal arterial spin labeling work-in-progress sequence. The other authors report no conflicts.FootnotesCirculation is available at www.ahajournals.org/journal/circThis manuscript was sent to Jeffrey Testani, Guest Editor, for review by expert referees, editorial decision, and final disposition.*M. C. Petrie, N. Sattar, and P. B. Mark contributed equally.This work was presented as a late-breaking clinical trial abstract at the American Society of Nephrology Kidney Week, November 4–7, 2021.For Sources of Funding and Disclosures, see page 366.Correspondence to: Patrick B, Mark, PhD, British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, 126 University Place, University of Glasgow, Glasgow, G12 8TA United Kingdom. Email patrick.[email protected]ac.ukReferences1. 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Efficacy of dapagliflozin on renal function and outcomes in patients with heart failure with reduced ejection fraction: results of DAPA-HF.Circulation. 2021; 143:298–309. doi: 10.1161/CIRCULATIONAHA.120.050391LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails July 26, 2022Vol 146, Issue 4 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.122.059851PMID: 35877829 Originally publishedJuly 25, 2022 Keywordskidneymagnetic resonance imagingempagliflozinheart failureclinical trialdiabetes mellitussodium-glucose transporter 2 inhibitorsPDF download Advertisement SubjectsCardiorenal SyndromeDiabetes, Type 2Heart FailureMagnetic Resonance Imaging (MRI)
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