Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus

Circulation
David Z I CherneyMaximilian von Eynatten

Abstract

The primary objective of this mechanistic open-label, stratified clinical trial was to determine the effect of 8 weeks' sodium glucose cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration in subjects with type 1 diabetes mellitus (T1D). Inulin (glomerular filtration rate; GFR) and paraaminohippurate (effective renal plasma flow) clearances were measured in individuals stratified based on having hyperfiltration (T1D-H, GFR ≥ 135 mL/min/1.73m(2), n=27) or normal GFR (T1D-N, GFR 90-134 mL/min/1.73m(2), n=13) at baseline. Renal function and circulating levels of renin-angiotensin-aldosterone system mediators and NO were measured under clamped euglycemic (4-6 mmol/L) and hyperglycemic (9-11 mmol/L) conditions at baseline and end of treatment. During clamped euglycemia, hyperfiltration was attenuated by -33 mL/min/1.73m(2) with empagliflozin in T1D-H, (GFR 172±23-139±25 mL/min/1.73 m(2), P<0.01). This effect was accompanied by declines in plasma NO and effective renal plasma flow and an increase in renal vascular resistance (all P<0.01). Similar significant effects on GFR and renal function parameters were observed during clamped hyperglycemia. In T1D-N, GFR, other renal function parameters, and plasma NO w...Continue Reading

References

May 1, 1984·Kidney International·R C Blantz, J C Pelayo
Mar 1, 1981·Kidney International·T H HostetterB M Brenner
Dec 16, 1998·Acta Physiologica Scandinavica·J KurkusA E Persson
Aug 14, 1999·Journal of the American Society of Nephrology : JASN·J A Miller
Dec 10, 1999·Journal of the American Society of Nephrology : JASN·V VallonH Osswald
Nov 13, 2001·Clinical and Experimental Pharmacology & Physiology·E R LumbersK J Gibson
Sep 5, 2002·Annual Review of Physiology·Jürgen Schnermann, David Z Levine
Jan 5, 2005·Hypertension·Stefan EngeliArya M Sharma
May 5, 2006·Journal of the American Society of Nephrology : JASN·Etienne B SochettJudith A Miller
Jul 1, 1935·The Journal of Clinical Investigation·J A Shannon, H W Smith
Jul 14, 2006·Kidney & Blood Pressure Research·Michiel SchreuderAns van Wijk
Jul 16, 2008·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Joaquim CaladoRené Santer
Sep 5, 2008·Experimental Diabetes Research·Slava MalatialiMario Barac-Nieto
Dec 31, 2008·Diabetes Care·James F ListFred T Fiedorek
Jul 3, 2009·The New England Journal of Medicine·Michael MauerRonald Klein
May 25, 2010·Diabetologia·G JerumsR J MacIsaac
Mar 5, 2011·Kidney International. Supplement·James F List, Jean M Whaley
May 25, 2011·Endocrine Reviews·Muhammad A Abdul-GhaniRalph A Defronzo
Sep 24, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Scott C ThomsonPrabhleen Singh
Nov 15, 2011·The New England Journal of Medicine·UNKNOWN DCCT/EDIC Research GroupBernard Zinman
Jan 19, 2012·World Journal of Diabetes·Alexa N Sasson, David Zi Cherney
Mar 3, 2012·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Celine FooteBruce Neal
Jul 10, 2012·Diabetes Care·Piero RuggenentiUNKNOWN GFR Study Investigators
Aug 3, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·David Z I CherneyEtienne B Sochett
Mar 8, 2013·Diabetes, Obesity & Metabolism·J-F YaleG Meininger
Mar 16, 2013·The Journal of Pharmacology and Experimental Therapeutics·Naoki KojimaRichard J Roman

❮ Previous
Next ❯

Citations

Jul 2, 2014·Current Opinion in Endocrinology, Diabetes, and Obesity·Petter BjornstadDavid M Maahs
May 6, 2014·Reviews in Endocrine & Metabolic Disorders·Jeppe Skov
Sep 27, 2014·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Katherine R TuttleMark E Molitch
Sep 7, 2014·Canadian Journal of Diabetes·David Z I Cherney, Bruce A Perkins
Dec 4, 2014·Current Opinion in Nephrology and Hypertension·Marko Škrtić, David Z I Cherney
Apr 5, 2016·Indian Journal of Endocrinology and Metabolism·Mathew John
Apr 29, 2015·Expert Opinion on Pharmacotherapy·Nordin M J HanssenMark E Cooper
Oct 11, 2014·Expert Opinion on Pharmacotherapy·Vidhya Jahagirdar, Anthony H Barnett
Sep 5, 2015·Expert Opinion on Pharmacotherapy·Kashif M Munir, Stephen N Davis
Dec 24, 2015·Expert Opinion on Drug Safety·Ian J NeelandDarren K McGuire
Apr 22, 2014·Expert Opinion on Investigational Drugs·Elizabeth M LamosStephen N Davis
Oct 24, 2015·Current Medical Research and Opinion·Vlado PerkovicGary Meininger
Aug 1, 2015·Rejuvenation Research·Sho-ichi Yamagishi, Takanori Matsui
Oct 21, 2015·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Bruce W Bode, Satish K Garg
Dec 24, 2015·Diabetes·Lisanne M M GommersJeroen H F de Baaij
Jan 26, 2016·Current Opinion in Nephrology and Hypertension·Ilkka TikkanenOdd Erik Johansen
Jan 29, 2016·European Heart Journal·David FitchettUNKNOWN EMPA-REG OUTCOME® trial investigators
Dec 5, 2015·Diabetes, Obesity & Metabolism·Marcel H A MuskietDaniël H van Raalte
Jan 1, 2015·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Janaka Karalliedde, Luigi Gnudi
Sep 26, 2015·Diabetes, Obesity & Metabolism·Surya Panicker RajeevJohn P H Wilding
Nov 4, 2015·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Jin-Soon SuhByoung Kyu Suh
Aug 26, 2015·Annals of the New York Academy of Sciences·Norm RosenthalKeith Demarest
Jun 3, 2015·Diabetic Medicine : a Journal of the British Diabetic Association·L MerkerUNKNOWN EMPA-REG EXTEND MET investigators
Nov 2, 2014·Kidney International·Richard E Gilbert
Nov 26, 2015·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Wendy Lane
Nov 17, 2015·Clinica Chimica Acta; International Journal of Clinical Chemistry·Danielle FortunaDouglas F Stickle
Dec 2, 2015·Clinical Medicine : Journal of the Royal College of Physicians of London·Frank WardPatrick T Murray
Mar 13, 2016·The Lancet. Diabetes & Endocrinology·Christian Seerup FrandsenSten Madsbad
Nov 18, 2015·Current Opinion in Nephrology and Hypertension·Aleksandra Novikov, Volker Vallon

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiology Journals

Discover the latest cardiology research in this collection of the top cardiology journals.

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.