Vascular occlusive disease poses a threat to kidney viability, but whether the events leading to injury and eventual fibrosis actually entail reduced oxygenation and regional tissue ischemia is unknown. Answering this question has been difficult because of the lack of an adequate method to assess tissue oxygenation in humans. BOLD (blood oxygen-level-dependent) magnetic resonance imaging detects changes in tissue deoxyhemoglobin during maneuvers that affect oxygen consumption, therefore this technique was used to image and analyze cortical and medullary segments of 50 kidneys in 25 subjects undergoing magnetic resonance (MR) angiography to diagnose renal artery stenosis (RAS). Magnetic rate of relaxation (R2*) positively correlates with deoxyhemoglobin levels and was therefore used as a surrogate measure of tissue oxygenation. Furosemide was administered to examine the effect of inhibiting energy-dependent electrolyte transport on tissue oxygenation in subjects with renovascular disease. In 21 kidneys with normal nephrograms, administration of furosemide led to a 20% decrease in medullary R2* (P Ͻ 0.01) and an 11.2% decrease in cortical R2*. In normal-size kidneys downstream of high-grade renal arterial stenoses, R2* was elevated at baseline, but fell after furosemide. In contrast, atrophic kidneys beyond totally occluded renal arteries demonstrated low levels of R2* that did not change after furosemide. In kidneys with multiple arteries, localized renal artery stenoses produced focal elevations of R2*, suggesting areas of deoxyhemoglobin accumulation. These results suggest that BOLD MR coupled with a method to suppress tubular oxygen consumption can be used to evaluate regional tissue oxygenation in the human kidney affected by vascular occlusive disease.
Imaging of the kidney using BOLD MR presents a major opportunity to examine differences in tissue oxygenation within the cortex and medulla applicable to human disease. We sought to define the differences between regions within kidneys and to optimize selection of regions of interest for study with 1.5 and 3 Tesla systems. Studies in 38 subjects were performed under baseline conditions and after administration of furosemide intravenously to examine changes in R2* as a result of suppressing oxygen consumption related to medullary tubular solute transport. These studies were carried out in patients with atherosclerotic renal artery stenosis (n= 24 kidneys) or essential hypertension or non-stenotic kidneys (n= 39). All patients but one were treated with agents to block the renin angiotensin system (ACE inhibitors or angiotensin receptor blockers). For each kidney, three levels (upper pole, hilum, and lower pole) were examined, including three individual segments (anterior, lateral, and posterior). Low basal R2* levels in kidney cortex (12.06 ± 0.84 sec-1) at 1.5 Tesla reflected robust blood flow and oxygenation and agreed closely with values obtained at 3.0 Tesla (13.62 ± 0.56 sec-1, NS). Coefficients of variation ranged between 15–20% between segments and levels at both field strengths. By contrast, inner medullary R2* levels were higher at 3 T (31.66 ± 0.74 sec-1) as compared to 1.5 T (22.19 ± 1.52 sec-1, p<.01). Medullary R2* values fell after furosemide administration fell reflecting reduced deoxyhemoglobin levels associated with blocked energy-dependent transport. The fall in medullary R2* at 3.0 Tesla (−12.61 ± 0.97 sec-1) was greater than observed at 1.5 T (−6.07 ± 1.38 sec-1, p<.05). Cortical R2* levels remained low after furosemide and did not vary with field strength. Correlations between measurements of defined cortical and medullary ROIs within kidneys were greater at each sampling level and segment at 3.0 T as compared o 1.5 T. For patients studied with 3.0 T, furosemide administration induced a lesser fall in R2* in post-stenotic kidneys at 3.0 T (−10.61 ± 1.61 sec-1) versus non-stenotic kidneys (−13.21 ± 0.72 sec-1, p<.05). This difference was not evident in comparisons made at 1.5 T. The magnitude of furosemide-suppressible oxygen consumption at 3.0 T (−43 %) corresponded more closely with reported experimental differences observed during direct measurement with tissue electrodes (45–50%) than changes measured at 1.5 T. These results indicate that BOLD MR measurements at high field strength can better distinguish discrete cortical and inner medullary regions of the kidney and approximate measured differences in oxygen tension. Maneuvers that reduce oxygen consumption related to tubular solute transport allow functional evaluation of the interstitial compartment as a function of tissue oxygenation. Impaired response to alterations in oxygen consumption can be detected at 3T more effectively than at 1.5 T and may provide real-time tools to examine developing parenchymal injury associated with impaired...
. Regional decreases in renal oxygenation during graded acute renal arterial stenosis: a case for renal ischemia. Am J Physiol Regul Integr Comp Physiol 296: R67-R71, 2009. First published October 29, 2008 doi:10.1152/ajpregu.90677.2008.-Ischemic nephropathy describes progressive renal failure, defined by significantly reduced glomerular filtration rate, and may be due to renal artery stenosis (RAS), a narrowing of the renal artery. It is unclear whether ischemia is present during RAS since a decrease in renal blood flow (RBF), O 2 delivery, and O2 consumption occurs. The present study tests the hypothesis that despite proportional changes in whole kidney O 2 delivery and consumption, acute progressive RAS leads to decreases in regional renal tissue O 2. Unilateral acute RAS was induced in eight pigs with an extravascular cuff. RBF was measured with an ultrasound flow probe. Cortical and medullary tissue oxygen ͑P t O 2 ͒ of the stenotic kidney was measured continuously with sensors during baseline, three sequentially graded decreases in RBF, and recovery. O 2 consumption decreased proportionally to O2 delivery during the graded stenosis (19 Ϯ 10.8, 48.2 Ϯ 9.1, 58.9 Ϯ 4.7 vs. 15.1 Ϯ 5, 35.4 Ϯ 3.5, 57 Ϯ 2.3%, respectively) while arterial venous O 2 differences were unchanged. Acute RAS produced a sharp reduction in O 2 efficiency for sodium reabsorption (P Ͻ 0.01). Cortical ͑P t O 2 ͒ decreases are exceeded by medullary decreases during stenosis (34.8 Ϯ 1.3%). Decreases in tissue oxygenation, more pronounced in the medulla than the cortex, occur despite proportional reductions in O 2 delivery and consumption. This demonstrates for the first time that hypoxia is present in the early stages of RAS and suggests a role for hypoxia in the pathophysiology of this disease. Furthermore, the notion that arteriovenous shunting and increased stoichiometric energy requirements are potential contributors toward ensuing hypoxia with graded and progressive acute RAS cannot be excluded.ischemia; renal tissue oxygenation; renal blood flow; pig THE TERM "ISCHEMIC NEPHROPATHY" has been used to describe progressive renal failure, defined by a significantly reduced glomerular filtration rate (GFR) or loss of renal parenchyma due to renal artery stenosis, a narrowing of one or more of the renal arteries. Ischemia, however, results from a rate of blood flow that is insufficient to satisfy metabolic demands, thereby leading to tissue hypoxia. There is little evidence to suggest that ischemic nephropathy is accompanied by renal tissue hypoxia (24). In fact, the kidney has a high blood flow relative to its weight (3), which results in very small arterial-venous differences in oxygenation, suggesting a large O 2 supply and limited O 2 consumption. Importantly, Nielsen et al. (15) found in patients with significant unilateral renal artery stenosis that O 2 consumption decreased with limited blood flow, suggesting that a decrease in O 2 supply is not enough to cause ischemic renal disease (22). Moreover, the reduced O 2 supply and demand s...
. 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...
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