Magnetic Resonance Imaging–Derived Renal Oxygenation and Perfusion During Continuous, Steady‐State Angiotensin‐II Infusion in Healthy Humans

Abstract

BackgroundThe role of kidney hypoxia is considered pivotal in the progression of chronic kidney disease. A widely used method to assess kidney oxygenation is blood oxygen level dependent (BOLD)–magnetic resonance imaging (MRI), but its interpretation remains problematic. The BOLD‐MRI signal is the result of kidney oxygen consumption (a proxy of glomerular filtration) and supply (ie, glomerular perfusion). Therefore, we hypothesized that with pharmacological modulation of kidney blood flow, renal oxygenation, as assessed by BOLD‐MRI, correlates to filtration fraction (ie, glomerular filtration rate/effective renal plasma flow) in healthy humans.Methods and ResultsEight healthy volunteers were subjected to continuous angiotensin‐II infusion at 0.3, 0.9, and 3.0 ng/kg per minute. At each dose, renal oxygenation and blood flow were assessed using BOLD and phase‐contrast MRI. Subsequently, “gold standard” glomerular filtration rate/effective renal plasma flow measurements were performed under the same conditions. Renal plasma flow decreased dose dependently from 660±146 to 467±103 mL/min per 1.73 m2 (F[3, 21]=33.3, P<0.001). Glomerular filtration rate decreased from 121±23 to 110±18 mL/min per 1.73 m2 (F[1.8, 2.4]=6.4, P=0.013). Cortical transverse relaxation rate (R2*; increases in R2* represent decreases in oxygenation) increased by 7.2±3.8% (F[3, 21]=7.37, P=0.001); medullar R2* did not change. Cortical R2* related to filtration fraction (R 2 0.46, P<0.001).ConclusionsBy direct comparison between “gold standard” kidney function measurements and BOLD MRI, we showed that cortical oxygenation measured by BOLD MRI relates poorly to glomerular filtration rate but is associated with filtration fraction. For future studies, there may be a need to include renal plasma flow measurements when employing renal BOLD‐MRI.

Exogenous and endogenous angiotensin‐II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow

“…The maintenance ofQ O 2 during infusion of AngII is probably due to the maintenance of GFR (as reflected in increased FF), and thus the filtered load of sodium. Consistent with this proposition, van der Bel et al recently showed a strong association of reduced cortical oxygenation (as assessed by blood oxygen level-dependent magnetic resonance imaging) with increased filtration fraction during intravenous infusion of angiotensin II in man (van der Bel et al 2016). Differences between the systemic and renal effects of AngII and PE were greater in conscious than in anaesthetised animals.…”

“…Consistent with this proposition, van der Bel et al recently showed a strong association of reduced cortical oxygenation (as assessed by blood oxygen level‐dependent magnetic resonance imaging) with increased filtration fraction during intravenous infusion of angiotensin II in man (van der Bel et al . ).…”

Renal Oxygenation in the Pathophysiology of Chronic Kidney Disease

“…Subsequently, another study demonstrated a dose-dependent decrease of renal blood flow accompanied by a minor decrease of oxygenation in the cortex, not in the medulla with continuous Ang II infusion in healthy humans (Bel et al, 2016). As discussed above, parenchymal hypoxia and fibrosis in the renal cortex of CKD patients using BOLD MRI and diffusion-weighted MRI has been shown (Inoue et al, 2011).…”

Functional Magnetic Resonance Imaging of the Kidneys—With and Without Gadolinium-Based Contrast

“…Early studies successfully validated the sensitivity of BOLD signals to diuretic-induced changes of renal oxygenation in healthy human subjects 30–32 . Reduced renal blood flow in healthy subjects by continuous angiotensin-II infusion 33 correlated with the GFR/RPF to cortical R 2 * ratio. As GFR and RPF represent oxygen consumption and delivery respectively, their ratio should directly relate to how much oxygen is left, or tissue oxygenation.…”