Determinations of renal cortical and medullary oxygenation using blood oxygen level-dependent magnetic resonance imaging and selective diuretics
Lizette Warner, James F Glockner, John Woollard, Stephen C Textor, Juan Carlos Romero, Lilach O Lerman, Lizette Warner, James F Glockner, John Woollard, Stephen C Textor, Juan Carlos Romero, Lilach O Lerman
Abstract
Objective: This study was undertaken to test the hypothesis that blood O2 level-dependent magnetic resonance imaging (BOLD MRI) can detect changes in cortical proximal tubule (PT) and medullary thick ascending limb of Henle (TAL) oxygenation consequent to successive administration of furosemide and acetazolamide (Az). Assessment of PT and TAL function could be useful to monitor renal disease states in vivo. Therefore, the adjunct use of diuretics that inhibit Na reabsorption selectively in PT and TAL, Az and furosemide, respectively, may help discern tubular function by using BOLD MRI to detect changes in tissue oxygenation.
Material and methods: BOLD MRI signal R2* (inversely related to oxygenation) and tissue oxygenation with intrarenal O2 probes were measured in pigs that received either furosemide (0.05 mg/kg) or Az (15 mg/kg) alone, Az sequentially after furosemide (n = 6 each, 15-minute intervals), or only saline vehicle (n = 3).
Results: R2* decreased in the cortex of Az-treated and medulla of furosemide-treated kidneys, corresponding to an increase in their tissue O2 assessed with probes. However, BOLD MRI also showed decreased cortical R2* following furosemide that was additive to the Az-induced decrease. Az administration, both alone and after furosemide, also decreased renal blood flow (-26% ± 3.5% and -29.2% ± 3%, respectively, P < 0.01).
Conclusion: These results suggest that an increase in medullary and cortical tissue O2 elicited by selective diuretics is detectable by BOLD MRI, but may be complicated by hemodynamic effects of the drugs. Therefore, the BOLD MRI signal may reflect functional changes additional to oxygenation, and needs to be interpreted cautiously.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3006042/bin/nihms-254529-f0001.jpg)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3006042/bin/nihms-254529-f0002.jpg)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3006042/bin/nihms-254529-f0003.jpg)
Figure 4
Change from baseline in tissue…
Figure 4
Change from baseline in tissue O 2 in the renal cortex (A) and…
Figure 5
Change from baseline in renal…
Figure 5
Change from baseline in renal blood flow (RBF) during administration of saline (s),…
- Determinants of intrarenal oxygenation. I. Effects of diuretics.Brezis M, Agmon Y, Epstein FH. Brezis M, et al. Am J Physiol. 1994 Dec;267(6 Pt 2):F1059-62. doi: 10.1152/ajprenal.1994.267.6.F1059. Am J Physiol. 1994. PMID: 7810692
- Human renal response to furosemide: Simultaneous oxygenation and perfusion measurements in cortex and medulla.Haddock B, Larsson HBW, Francis S, Andersen UB. Haddock B, et al. Acta Physiol (Oxf). 2019 Sep;227(1):e13292. doi: 10.1111/apha.13292. Epub 2019 May 21. Acta Physiol (Oxf). 2019. PMID: 31046189 Free PMC article.
- Increased hypoxia and reduced renal tubular response to furosemide detected by BOLD magnetic resonance imaging in swine renovascular hypertension.Gomez SI, Warner L, Haas JA, Bolterman RJ, Textor SC, Lerman LO, Romero JC. Gomez SI, et al. Am J Physiol Renal Physiol. 2009 Oct;297(4):F981-6. doi: 10.1152/ajprenal.90757.2008. Epub 2009 Jul 29. Am J Physiol Renal Physiol. 2009. PMID: 19640896 Free PMC article.
- Blood oxygen level-dependent (BOLD) MRI in renovascular hypertension.Gloviczki ML, Lerman LO, Textor SC. Gloviczki ML, et al. Curr Hypertens Rep. 2011 Oct;13(5):370-7. doi: 10.1007/s11906-011-0218-7. Curr Hypertens Rep. 2011. PMID: 21833688 Free PMC article. Review.
- How bold is blood oxygenation level-dependent (BOLD) magnetic resonance imaging of the kidney? Opportunities, challenges and future directions.Niendorf T, Pohlmann A, Arakelyan K, Flemming B, Cantow K, Hentschel J, Grosenick D, Ladwig M, Reimann H, Klix S, Waiczies S, Seeliger E. Niendorf T, et al. Acta Physiol (Oxf). 2015 Jan;213(1):19-38. doi: 10.1111/apha.12393. Epub 2014 Sep 30. Acta Physiol (Oxf). 2015. PMID: 25204811 Review.
- Noninvasive assessment of kidney dysfunction in children by using blood oxygenation level-dependent MRI and intravoxel incoherent motion diffusion-weighted imaging.Liang P, Chen Y, Li S, Xu C, Yuan G, Hu D, Kamel I, Zhang Y, Li Z. Liang P, et al. Insights Imaging. 2021 Oct 21;12(1):146. doi: 10.1186/s13244-021-01091-6. Insights Imaging. 2021. PMID: 34674043 Free PMC article.
- Superimposition of metabolic syndrome magnifies post-stenotic kidney injury in dyslipidemic pigs.Song T, Zhao Y, Zhu X, Eirin A, Krier JD, Tang H, Jordan KL, Lerman A, Lerman LO. Song T, et al. Am J Transl Res. 2021 Aug 15;13(8):8965-8976. eCollection 2021. Am J Transl Res. 2021. PMID: 34540008 Free PMC article.
- Perspectives on the Role of Magnetic Resonance Imaging (MRI) for Noninvasive Evaluation of Diabetic Kidney Disease.Mora-Gutiérrez JM, Fernández-Seara MA, Echeverria-Chasco R, Garcia-Fernandez N. Mora-Gutiérrez JM, et al. J Clin Med. 2021 Jun 2;10(11):2461. doi: 10.3390/jcm10112461. J Clin Med. 2021. PMID: 34199385 Free PMC article. Review.
- The renal microcirculation in chronic kidney disease: novel diagnostic methods and therapeutic perspectives.Li S, Wang F, Sun D. Li S, et al. Cell Biosci. 2021 May 17;11(1):90. doi: 10.1186/s13578-021-00606-4. Cell Biosci. 2021. PMID: 34001267 Free PMC article. Review.
- Reversible (Patho)Physiologically Relevant Test Interventions: Rationale and Examples.Cantow K, Ladwig-Wiegard M, Flemming B, Fekete A, Hosszu A, Seeliger E. Cantow K, et al. Methods Mol Biol. 2021;2216:57-73. doi: 10.1007/978-1-0716-0978-1_4. Methods Mol Biol. 2021. PMID: 33475994 Free PMC article.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Analysis of Variance
- Animals
- Disease Models, Animal
- Diuretics / pharmacology*
- Furosemide / pharmacology*
- Glomerular Filtration Rate
- Hemodynamics
- Kidney Cortex / blood supply*
- Kidney Cortex / drug effects
- Kidney Cortex / pathology
- Kidney Medulla / blood supply*
- Kidney Medulla / drug effects
- Kidney Medulla / pathology
- Magnetic Resonance Imaging / instrumentation*
- Magnetic Resonance Imaging / methods
- Oxygen Consumption / drug effects*
- Swine
- Diuretics
- Furosemide
- R01 HL077131/HL/NHLBI NIH HHS/United States
- R21 DK077013/DK/NIDDK NIH HHS/United States
- F31 HL094060/HL/NHLBI NIH HHS/United States
- R01 HL077131-05/HL/NHLBI NIH HHS/United States
- HL085307/HL/NHLBI NIH HHS/United States
- R01 DK073608/DK/NIDDK NIH HHS/United States
- R01 HL016496/HL/NHLBI NIH HHS/United States
- 1F31HL094060/HL/NHLBI NIH HHS/United States
- P01 HL085307-04/HL/NHLBI NIH HHS/United States
- HL16496/HL/NHLBI NIH HHS/United States
- DK77013/DK/NIDDK NIH HHS/United States
- HL77131/HL/NHLBI NIH HHS/United States
- R01 DK073608-04/DK/NIDDK NIH HHS/United States
- R21 DK077013-02/DK/NIDDK NIH HHS/United States
- P01 HL085307/HL/NHLBI NIH HHS/United States
- DK73608/DK/NIDDK NIH HHS/United States
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
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![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3006042/bin/nihms-254529-f0004.jpg)
Figure 5
Change from baseline in renal…
Figure 5
Change from baseline in renal blood flow (RBF) during administration of saline (s),…
- Determinants of intrarenal oxygenation. I. Effects of diuretics.Brezis M, Agmon Y, Epstein FH. Brezis M, et al. Am J Physiol. 1994 Dec;267(6 Pt 2):F1059-62. doi: 10.1152/ajprenal.1994.267.6.F1059. Am J Physiol. 1994. PMID: 7810692
- Human renal response to furosemide: Simultaneous oxygenation and perfusion measurements in cortex and medulla.Haddock B, Larsson HBW, Francis S, Andersen UB. Haddock B, et al. Acta Physiol (Oxf). 2019 Sep;227(1):e13292. doi: 10.1111/apha.13292. Epub 2019 May 21. Acta Physiol (Oxf). 2019. PMID: 31046189 Free PMC article.
- Increased hypoxia and reduced renal tubular response to furosemide detected by BOLD magnetic resonance imaging in swine renovascular hypertension.Gomez SI, Warner L, Haas JA, Bolterman RJ, Textor SC, Lerman LO, Romero JC. Gomez SI, et al. Am J Physiol Renal Physiol. 2009 Oct;297(4):F981-6. doi: 10.1152/ajprenal.90757.2008. Epub 2009 Jul 29. Am J Physiol Renal Physiol. 2009. PMID: 19640896 Free PMC article.
- Blood oxygen level-dependent (BOLD) MRI in renovascular hypertension.Gloviczki ML, Lerman LO, Textor SC. Gloviczki ML, et al. Curr Hypertens Rep. 2011 Oct;13(5):370-7. doi: 10.1007/s11906-011-0218-7. Curr Hypertens Rep. 2011. PMID: 21833688 Free PMC article. Review.
- How bold is blood oxygenation level-dependent (BOLD) magnetic resonance imaging of the kidney? Opportunities, challenges and future directions.Niendorf T, Pohlmann A, Arakelyan K, Flemming B, Cantow K, Hentschel J, Grosenick D, Ladwig M, Reimann H, Klix S, Waiczies S, Seeliger E. Niendorf T, et al. Acta Physiol (Oxf). 2015 Jan;213(1):19-38. doi: 10.1111/apha.12393. Epub 2014 Sep 30. Acta Physiol (Oxf). 2015. PMID: 25204811 Review.
- Noninvasive assessment of kidney dysfunction in children by using blood oxygenation level-dependent MRI and intravoxel incoherent motion diffusion-weighted imaging.Liang P, Chen Y, Li S, Xu C, Yuan G, Hu D, Kamel I, Zhang Y, Li Z. Liang P, et al. Insights Imaging. 2021 Oct 21;12(1):146. doi: 10.1186/s13244-021-01091-6. Insights Imaging. 2021. PMID: 34674043 Free PMC article.
- Superimposition of metabolic syndrome magnifies post-stenotic kidney injury in dyslipidemic pigs.Song T, Zhao Y, Zhu X, Eirin A, Krier JD, Tang H, Jordan KL, Lerman A, Lerman LO. Song T, et al. Am J Transl Res. 2021 Aug 15;13(8):8965-8976. eCollection 2021. Am J Transl Res. 2021. PMID: 34540008 Free PMC article.
- Perspectives on the Role of Magnetic Resonance Imaging (MRI) for Noninvasive Evaluation of Diabetic Kidney Disease.Mora-Gutiérrez JM, Fernández-Seara MA, Echeverria-Chasco R, Garcia-Fernandez N. Mora-Gutiérrez JM, et al. J Clin Med. 2021 Jun 2;10(11):2461. doi: 10.3390/jcm10112461. J Clin Med. 2021. PMID: 34199385 Free PMC article. Review.
- The renal microcirculation in chronic kidney disease: novel diagnostic methods and therapeutic perspectives.Li S, Wang F, Sun D. Li S, et al. Cell Biosci. 2021 May 17;11(1):90. doi: 10.1186/s13578-021-00606-4. Cell Biosci. 2021. PMID: 34001267 Free PMC article. Review.
- Reversible (Patho)Physiologically Relevant Test Interventions: Rationale and Examples.Cantow K, Ladwig-Wiegard M, Flemming B, Fekete A, Hosszu A, Seeliger E. Cantow K, et al. Methods Mol Biol. 2021;2216:57-73. doi: 10.1007/978-1-0716-0978-1_4. Methods Mol Biol. 2021. PMID: 33475994 Free PMC article.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Analysis of Variance
- Animals
- Disease Models, Animal
- Diuretics / pharmacology*
- Furosemide / pharmacology*
- Glomerular Filtration Rate
- Hemodynamics
- Kidney Cortex / blood supply*
- Kidney Cortex / drug effects
- Kidney Cortex / pathology
- Kidney Medulla / blood supply*
- Kidney Medulla / drug effects
- Kidney Medulla / pathology
- Magnetic Resonance Imaging / instrumentation*
- Magnetic Resonance Imaging / methods
- Oxygen Consumption / drug effects*
- Swine
- Diuretics
- Furosemide
- R01 HL077131/HL/NHLBI NIH HHS/United States
- R21 DK077013/DK/NIDDK NIH HHS/United States
- F31 HL094060/HL/NHLBI NIH HHS/United States
- R01 HL077131-05/HL/NHLBI NIH HHS/United States
- HL085307/HL/NHLBI NIH HHS/United States
- R01 DK073608/DK/NIDDK NIH HHS/United States
- R01 HL016496/HL/NHLBI NIH HHS/United States
- 1F31HL094060/HL/NHLBI NIH HHS/United States
- P01 HL085307-04/HL/NHLBI NIH HHS/United States
- HL16496/HL/NHLBI NIH HHS/United States
- DK77013/DK/NIDDK NIH HHS/United States
- HL77131/HL/NHLBI NIH HHS/United States
- R01 DK073608-04/DK/NIDDK NIH HHS/United States
- R21 DK077013-02/DK/NIDDK NIH HHS/United States
- P01 HL085307/HL/NHLBI NIH HHS/United States
- DK73608/DK/NIDDK NIH HHS/United States
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3006042/bin/nihms-254529-f0005.jpg)
Source: PubMed