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The hemodynamic and metabolic effects of spironolactone treatment in acute kidney injury assessed by hyperpolarized MRI

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The hemodynamic and metabolic effects of spironolactone treatment in acute kidney injury assessed by hyperpolarized MRI. / Lindhardt, Jakob Lykke; Nielsen, Per Mose; Hansen, Esben Søvsø Szocska; Qi, Haiyun; Tougaard, Rasmus Stilling; Mariager, Christian Østergaard; Bertelsen, Lotte Bonde; Kim, Won Yong; Laustsen, Christoffer.

I: NMR in Biomedicine, Bind 33, Nr. 10, e4371, 10.2020.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{f158c90e78f44c61b940fb74c28590a3,
title = "The hemodynamic and metabolic effects of spironolactone treatment in acute kidney injury assessed by hyperpolarized MRI",
abstract = "Renal ischemia-reperfusion injury (IRI) is one of the most common types of acute kidney injury. Spironolactone has shown promising kidney protective effects in renal IRI in rats. We investigated the hemodynamic and metabolic effects of spironolactone (100 mg/kg) administered immediately after 40 min unilateral kidney ischemia in rats. Hyperpolarized MRI using co-polarized [1-13 C]pyruvate and [13 C,15 N2 ]urea as well as 1 H dynamic contrast-enhanced (DCE) MRI was performed 24 h after induction of ischemia. We found a significant decrease in renal blood flow (RBF) in the ischemic kidney compared with the contralateral one measured using DCE and [13 C,15 N2 ]urea. The RBF measured using [1-13 C]pyruvate and [13 C,15 N2 ]urea was significantly altered by spironolactone. The RBFs in the ischemic kidney compared with the contralateral kidney were decreased similarly as measured using both [13 C,15 N2 ]urea and [1-13 C]pyruvate in the spironolactone-treated group. Spironolactone treatment increased the perfusion-corrected pyruvate metabolism by 54% in both the ischemic and contralateral kidney. Furthermore, we showed a correlation between vascular permeability using a histological Evans blue analysis and the ratio of the volumes of distribution (VoDs), ie VoD-[13 C,15 N2 ]urea/VoD-[1-13 C]pyruvate. This suggests that [13 C,15 N2 ]urea/[1-13 C]pyruvate VoD ratio may be a novel indicator of renal vascular permeability associated with renal damage in rodents.",
keywords = "AKI, ALDOSTERONE, C-13, Hyperpolarization, Kidney, MINERALOCORTICOID RECEPTOR ANTAGONISM, MRI, OPEN-SOURCE SOFTWARE, PERFUSION, RENAL ISCHEMIA, Renal Metabolism",
author = "Lindhardt, {Jakob Lykke} and Nielsen, {Per Mose} and Hansen, {Esben S{\o}vs{\o} Szocska} and Haiyun Qi and Tougaard, {Rasmus Stilling} and Mariager, {Christian {\O}stergaard} and Bertelsen, {Lotte Bonde} and Kim, {Won Yong} and Christoffer Laustsen",
note = "{\textcopyright} 2020 John Wiley & Sons, Ltd.",
year = "2020",
month = oct,
doi = "10.1002/nbm.4371",
language = "English",
volume = "33",
journal = "N M R in Biomedicine (Online)",
issn = "1099-1492",
publisher = "JohnWiley & Sons Ltd.",
number = "10",

}

RIS

TY - JOUR

T1 - The hemodynamic and metabolic effects of spironolactone treatment in acute kidney injury assessed by hyperpolarized MRI

AU - Lindhardt, Jakob Lykke

AU - Nielsen, Per Mose

AU - Hansen, Esben Søvsø Szocska

AU - Qi, Haiyun

AU - Tougaard, Rasmus Stilling

AU - Mariager, Christian Østergaard

AU - Bertelsen, Lotte Bonde

AU - Kim, Won Yong

AU - Laustsen, Christoffer

N1 - © 2020 John Wiley & Sons, Ltd.

PY - 2020/10

Y1 - 2020/10

N2 - Renal ischemia-reperfusion injury (IRI) is one of the most common types of acute kidney injury. Spironolactone has shown promising kidney protective effects in renal IRI in rats. We investigated the hemodynamic and metabolic effects of spironolactone (100 mg/kg) administered immediately after 40 min unilateral kidney ischemia in rats. Hyperpolarized MRI using co-polarized [1-13 C]pyruvate and [13 C,15 N2 ]urea as well as 1 H dynamic contrast-enhanced (DCE) MRI was performed 24 h after induction of ischemia. We found a significant decrease in renal blood flow (RBF) in the ischemic kidney compared with the contralateral one measured using DCE and [13 C,15 N2 ]urea. The RBF measured using [1-13 C]pyruvate and [13 C,15 N2 ]urea was significantly altered by spironolactone. The RBFs in the ischemic kidney compared with the contralateral kidney were decreased similarly as measured using both [13 C,15 N2 ]urea and [1-13 C]pyruvate in the spironolactone-treated group. Spironolactone treatment increased the perfusion-corrected pyruvate metabolism by 54% in both the ischemic and contralateral kidney. Furthermore, we showed a correlation between vascular permeability using a histological Evans blue analysis and the ratio of the volumes of distribution (VoDs), ie VoD-[13 C,15 N2 ]urea/VoD-[1-13 C]pyruvate. This suggests that [13 C,15 N2 ]urea/[1-13 C]pyruvate VoD ratio may be a novel indicator of renal vascular permeability associated with renal damage in rodents.

AB - Renal ischemia-reperfusion injury (IRI) is one of the most common types of acute kidney injury. Spironolactone has shown promising kidney protective effects in renal IRI in rats. We investigated the hemodynamic and metabolic effects of spironolactone (100 mg/kg) administered immediately after 40 min unilateral kidney ischemia in rats. Hyperpolarized MRI using co-polarized [1-13 C]pyruvate and [13 C,15 N2 ]urea as well as 1 H dynamic contrast-enhanced (DCE) MRI was performed 24 h after induction of ischemia. We found a significant decrease in renal blood flow (RBF) in the ischemic kidney compared with the contralateral one measured using DCE and [13 C,15 N2 ]urea. The RBF measured using [1-13 C]pyruvate and [13 C,15 N2 ]urea was significantly altered by spironolactone. The RBFs in the ischemic kidney compared with the contralateral kidney were decreased similarly as measured using both [13 C,15 N2 ]urea and [1-13 C]pyruvate in the spironolactone-treated group. Spironolactone treatment increased the perfusion-corrected pyruvate metabolism by 54% in both the ischemic and contralateral kidney. Furthermore, we showed a correlation between vascular permeability using a histological Evans blue analysis and the ratio of the volumes of distribution (VoDs), ie VoD-[13 C,15 N2 ]urea/VoD-[1-13 C]pyruvate. This suggests that [13 C,15 N2 ]urea/[1-13 C]pyruvate VoD ratio may be a novel indicator of renal vascular permeability associated with renal damage in rodents.

KW - AKI

KW - ALDOSTERONE

KW - C-13

KW - Hyperpolarization

KW - Kidney

KW - MINERALOCORTICOID RECEPTOR ANTAGONISM

KW - MRI

KW - OPEN-SOURCE SOFTWARE

KW - PERFUSION

KW - RENAL ISCHEMIA

KW - Renal Metabolism

UR - http://www.scopus.com/inward/record.url?scp=85088265443&partnerID=8YFLogxK

U2 - 10.1002/nbm.4371

DO - 10.1002/nbm.4371

M3 - Journal article

C2 - 32691467

VL - 33

JO - N M R in Biomedicine (Online)

JF - N M R in Biomedicine (Online)

SN - 1099-1492

IS - 10

M1 - e4371

ER -