Increased hypoxia and reduced renal tubular response to furosemide detected by BOLD magnetic resonance imaging in swine renovascular hypertension

Abstract

. Increased hypoxia and reduced renal tubular response to furosemide detected by BOLD magnetic resonance imaging in swine renovascular hypertension. Am J Physiol Renal Physiol 297: F981-F986, 2009. First published July 29, 2009 doi:10.1152/ajprenal.90757.2008.-Oxygen consumption beyond the proximal tubule is mainly determined by active solute reabsorption, especially in the thick ascending limb of the Loop of Henle. Furosemide-induced suppression of oxygen consumption (FSOC) involves inhibition of sodium transport in this segment, which is normally accompanied by a marked decrease in the intrarenal deoxyhemoglobin detectable by blood oxygen level-dependent (BOLD)-magnetic resonance imaging (MRI). This study tested the hypothesis that the magnitude of BOLD-MRI signal change after furosemide is related to impaired renal function in renovascular hypertension. In 16 pigs with unilateral renal artery stenosis, renal hemodynamics, function, and tubular function (FSOC and fluid concentration capacity) were evaluated in both kidneys using MR and multidetector computerized tomography (MDCT) imaging. Animals with adequate FSOC (23.6 Ϯ 2.2%, P Ͼ 0.05 vs. baseline) exhibited a mean arterial pressure (MAP) of 113 Ϯ 7 mmHg, and relatively preserved glomerular filtration rate (GFR) of 60 Ϯ 4.5 ml/min, comparable to their contralateral kidney (66 Ϯ 4 ml/min, P Ͼ 0.05). In contrast, animals with low FSOC (3.1 Ϯ 2.1%, P ϭ NS vs. baseline) had MAP of 124 Ϯ 9 mmHg and GFR (22 Ϯ 6 ml/min) significantly lower than the contralateral kidneys (66 Ϯ 4 ml/min, P Ͻ 0.05). The group with preserved GFR and FSOC showed an increase in intratubular fluid concentration as assessed by MDCT that was greater than that observed in the low GFR group, suggesting better preservation of tubular function in the former group. These results suggest that changes in BOLD-MRI after furosemide can differentiate between underperfused kidneys with preserved tubular function and those with tubular dysfunction. This approach may allow more detailed physiologic evaluation of poststenotic kidneys in renovascular hypertension than previously possible.renal artery stenosis; oxygenation THE EVALUATION AND MANAGEMENT of renovascular hypertension have been and continue to be a subject of intense debate (39,43). The uncertainties are mostly due to difficulties in assessing individual renal function and viability in kidneys that are unequally perfused (15,34). Large vessel occlusion of the renal circulation is known to affect blood flow and glomerular filtration in the poststenotic kidney. As filtration falls, fractional sodium reabsorption increases, leading to reduced sodium excretion in the affected kidney. Because sodium reabsorption in tubular segments beyond the proximal tubule requires energy, this process increases kidney work and oxygen consumption. In more severe stenoses, glomerular filtration rate (GFR) and sodium delivery eventually fall, while overall sodium reabsorption and oxygen consumption decline. In addition to tubular work, a decrease in oxygen deliv...

Human Renovascular Disease: Estimating Fractional Tissue Hypoxia to Analyze Blood Oxygen Level–dependent MR

“…ROIs = 1-7. with either contralateral kidneys or kidneys with EH. These observations extend the results of Gomez et al (28), who reported reduced furosemide-suppressible oxygen consumption in the kidneys beyond the stenosis with reduced GFR in a swine model. In this study, we further compared BOLD MR images obtained from multiple axial sections from the same kidneys.…”

Hypoxia: The Force that Drives Chronic Kidney Disease

“…Specifically, the oxygen tension of the kidney cortex and medulla has been shown to be approximately 10 mm Hg lower than normal in spontaneously hypertensive rats and other models of hypertension as well as in hypertensive patients. 15,89,[144][145][146] The role of hypertension in the progression of CKD was first described in 1914 by Volhard and Fahr. 13 Subsequently, it was appreciated that hypertension predisposes to kidney failure by inducing renal hypoxia.…”

Blood oxygenation level-dependent MRI for assessment of renal oxygenation

“…These investigators concluded that the response to furosemide can be used to distinguish between viable parenchyma (baseline hypoxia with amelioration after furosemide) and nonviable renal tissue (baseline hyperoxia without response to furosemide). Similarly, Gomez et al 72 utilized BOLD MRI in a swine model of renal artery stenosis and found that the ability of furosemide to suppress oxygen consumption in stenotic kidneys with reduced GFR was blunted compared with stenotic kidneys with preserved GFR. Consistent with the observations of Textor et al, 27 Chrysochou et al 73 found that in humans with atherosclerotic renal artery stenosis, stenotic kidneys with renal hypoxia detected by BOLD MRI were more likely to show a favorable renal functional response to revascularization.…”