The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial

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Standard

The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial. / van Bommel, Erik J.M.; Muskiet, Marcel H.A.; van Baar, Michaël J.B.; Tonneijck, Lennart; Smits, Mark M.; Emanuel, Anna L.; Bozovic, Andrea; Danser, A. H.Jan; Geurts, Frank; Hoorn, Ewout J.; Touw, Daan J.; Larsen, Emil L.; Poulsen, Henrik E.; Kramer, Mark H.H.; Nieuwdorp, Max; Joles, Jaap A.; van Raalte, Daniël H.

I: Kidney International, Bind 97, Nr. 1, 01.2020, s. 202-212.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

van Bommel, EJM, Muskiet, MHA, van Baar, MJB, Tonneijck, L, Smits, MM, Emanuel, AL, Bozovic, A, Danser, AHJ, Geurts, F, Hoorn, EJ, Touw, DJ, Larsen, EL, Poulsen, HE, Kramer, MHH, Nieuwdorp, M, Joles, JA & van Raalte, DH 2020, 'The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial', Kidney International, bind 97, nr. 1, s. 202-212. https://doi.org/10.1016/j.kint.2019.09.013

APA

van Bommel, E. J. M., Muskiet, M. H. A., van Baar, M. J. B., Tonneijck, L., Smits, M. M., Emanuel, A. L., Bozovic, A., Danser, A. H. J., Geurts, F., Hoorn, E. J., Touw, D. J., Larsen, E. L., Poulsen, H. E., Kramer, M. H. H., Nieuwdorp, M., Joles, J. A., & van Raalte, D. H. (2020). The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial. Kidney International, 97(1), 202-212. https://doi.org/10.1016/j.kint.2019.09.013

Vancouver

van Bommel EJM, Muskiet MHA, van Baar MJB, Tonneijck L, Smits MM, Emanuel AL o.a. The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial. Kidney International. 2020 jan.;97(1):202-212. https://doi.org/10.1016/j.kint.2019.09.013

Author

van Bommel, Erik J.M. ; Muskiet, Marcel H.A. ; van Baar, Michaël J.B. ; Tonneijck, Lennart ; Smits, Mark M. ; Emanuel, Anna L. ; Bozovic, Andrea ; Danser, A. H.Jan ; Geurts, Frank ; Hoorn, Ewout J. ; Touw, Daan J. ; Larsen, Emil L. ; Poulsen, Henrik E. ; Kramer, Mark H.H. ; Nieuwdorp, Max ; Joles, Jaap A. ; van Raalte, Daniël H. / The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial. I: Kidney International. 2020 ; Bind 97, Nr. 1. s. 202-212.

Bibtex

@article{f4e5b42b245b41b2b9a055eb2064bdbb,
title = "The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial",
abstract = "Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve hard renal outcomes in type 2 diabetes. This is possibly explained by the fact that SGLT2i normalize the measured glomerular filtration rate (mGFR) by increasing renal vascular resistance, as was shown in young people with type 1 diabetes and glomerular hyperfiltration. Therefore, we compared the renal hemodynamic effects of dapagliflozin with gliclazide in type 2 diabetes. The mGFR and effective renal plasma flow were assessed using inulin and para-aminohippurate clearances in the fasted state, during clamped euglycemia (5 mmol/L) and during clamped hyperglycemia (15 mmol/L). Filtration fraction and renal vascular resistance were calculated. Additionally, factors known to modulate renal hemodynamics were measured. In 44 people with type 2 diabetes on metformin monotherapy (Hemoglobin A1c 7.4%, mGFR 113 mL/min), dapagliflozin versus gliclazide reduced mGFR by 5, 10, and 12 mL/min in the consecutive phases while both agents similarly improved Hemoglobin A1c (-0.48% vs -0.65%). Dapagliflozin also reduced filtration fraction without increasing renal vascular resistance, and increased urinary adenosine and prostaglandin concentrations. Gliclazide did not consistently alter renal hemodynamic parameters. Thus, beyond glucose control, SGLT2i reduce mGFR and filtration fraction in type 2 diabetes. The fact that renal vascular resistance was not increased by dapagliflozin suggests that this is due to post-glomerular vasodilation rather than pre-glomerular vasoconstriction.",
keywords = "diabetic kidney disease, renal hemodynamics, SGLT2 inhibition, type 2 diabetes",
author = "{van Bommel}, {Erik J.M.} and Muskiet, {Marcel H.A.} and {van Baar}, {Micha{\"e}l J.B.} and Lennart Tonneijck and Smits, {Mark M.} and Emanuel, {Anna L.} and Andrea Bozovic and Danser, {A. H.Jan} and Frank Geurts and Hoorn, {Ewout J.} and Touw, {Daan J.} and Larsen, {Emil L.} and Poulsen, {Henrik E.} and Kramer, {Mark H.H.} and Max Nieuwdorp and Joles, {Jaap A.} and {van Raalte}, {Dani{\"e}l H.}",
year = "2020",
month = jan,
doi = "10.1016/j.kint.2019.09.013",
language = "English",
volume = "97",
pages = "202--212",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial

AU - van Bommel, Erik J.M.

AU - Muskiet, Marcel H.A.

AU - van Baar, Michaël J.B.

AU - Tonneijck, Lennart

AU - Smits, Mark M.

AU - Emanuel, Anna L.

AU - Bozovic, Andrea

AU - Danser, A. H.Jan

AU - Geurts, Frank

AU - Hoorn, Ewout J.

AU - Touw, Daan J.

AU - Larsen, Emil L.

AU - Poulsen, Henrik E.

AU - Kramer, Mark H.H.

AU - Nieuwdorp, Max

AU - Joles, Jaap A.

AU - van Raalte, Daniël H.

PY - 2020/1

Y1 - 2020/1

N2 - Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve hard renal outcomes in type 2 diabetes. This is possibly explained by the fact that SGLT2i normalize the measured glomerular filtration rate (mGFR) by increasing renal vascular resistance, as was shown in young people with type 1 diabetes and glomerular hyperfiltration. Therefore, we compared the renal hemodynamic effects of dapagliflozin with gliclazide in type 2 diabetes. The mGFR and effective renal plasma flow were assessed using inulin and para-aminohippurate clearances in the fasted state, during clamped euglycemia (5 mmol/L) and during clamped hyperglycemia (15 mmol/L). Filtration fraction and renal vascular resistance were calculated. Additionally, factors known to modulate renal hemodynamics were measured. In 44 people with type 2 diabetes on metformin monotherapy (Hemoglobin A1c 7.4%, mGFR 113 mL/min), dapagliflozin versus gliclazide reduced mGFR by 5, 10, and 12 mL/min in the consecutive phases while both agents similarly improved Hemoglobin A1c (-0.48% vs -0.65%). Dapagliflozin also reduced filtration fraction without increasing renal vascular resistance, and increased urinary adenosine and prostaglandin concentrations. Gliclazide did not consistently alter renal hemodynamic parameters. Thus, beyond glucose control, SGLT2i reduce mGFR and filtration fraction in type 2 diabetes. The fact that renal vascular resistance was not increased by dapagliflozin suggests that this is due to post-glomerular vasodilation rather than pre-glomerular vasoconstriction.

AB - Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve hard renal outcomes in type 2 diabetes. This is possibly explained by the fact that SGLT2i normalize the measured glomerular filtration rate (mGFR) by increasing renal vascular resistance, as was shown in young people with type 1 diabetes and glomerular hyperfiltration. Therefore, we compared the renal hemodynamic effects of dapagliflozin with gliclazide in type 2 diabetes. The mGFR and effective renal plasma flow were assessed using inulin and para-aminohippurate clearances in the fasted state, during clamped euglycemia (5 mmol/L) and during clamped hyperglycemia (15 mmol/L). Filtration fraction and renal vascular resistance were calculated. Additionally, factors known to modulate renal hemodynamics were measured. In 44 people with type 2 diabetes on metformin monotherapy (Hemoglobin A1c 7.4%, mGFR 113 mL/min), dapagliflozin versus gliclazide reduced mGFR by 5, 10, and 12 mL/min in the consecutive phases while both agents similarly improved Hemoglobin A1c (-0.48% vs -0.65%). Dapagliflozin also reduced filtration fraction without increasing renal vascular resistance, and increased urinary adenosine and prostaglandin concentrations. Gliclazide did not consistently alter renal hemodynamic parameters. Thus, beyond glucose control, SGLT2i reduce mGFR and filtration fraction in type 2 diabetes. The fact that renal vascular resistance was not increased by dapagliflozin suggests that this is due to post-glomerular vasodilation rather than pre-glomerular vasoconstriction.

KW - diabetic kidney disease

KW - renal hemodynamics

KW - SGLT2 inhibition

KW - type 2 diabetes

U2 - 10.1016/j.kint.2019.09.013

DO - 10.1016/j.kint.2019.09.013

M3 - Journal article

C2 - 31791665

AN - SCOPUS:85075994597

VL - 97

SP - 202

EP - 212

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 1

ER -

ID: 240242499