Kidney Oxygenation Research Articles

286 TELEMETRY-BASED OXYGEN SENSOR TO CONTINUOUSLY MONITOR KIDNEY OXYGENATION IN CONSCIOUS RATS; A NEW PLATFORM FOR EXPLORING DEVELOPMENT OF RENAL DISEASE

Objectives: Disturbed kidney oxygenation, i.e. renal hypoxia, may contribute to initiation and progression of both chronic kidney disease and acute kidney injury. A critical barrier to investigate this is the lack of available technology to chronically measure kidney tissue oxygenation. We have developed a novel solution for chronic measurement of oxygen concentration in the kidney. Methods: Using a telemetry-based carbon paste oxygen electrode we continuously recorded oxygen concentration in the inner medulla for 6 weeks in rats, unhindered by anaesthesia or restraint. The implantable potentiostat allows for potentially lifetime monitoring through the use of inductive powering of the implanted telemeter (Telemetry Research Ltd, Auckland, New Zealand). Results: Oxygen concentration values were stable over time and comparable between animals. Within an animal the level of tissue oxygen slightly increased over time from 7 days after implantation until 3 weeks. When the average of day 5, 6 and 7 is considered as baseline, oxygen concentration increased by 6-66% with a coefficient of variation of 22%. We observed a reproducible response to repeatedly applied changes in inspired oxygen. Hypoxia (10% oxygen) decreased medullary oxygen concentration by 48 ± 7% while hyperoxia (100% oxygen) increased it by 76 ± 5%. Three weeks after implantation, there was little fibrosis around the implanted electrodes. Conclusions: These findings illustrate the possibility of monitoring renal tissue oxygen concentration in conscious animals. This technology provides a platform for the investigation of the role of tissue hypoxia in development of kidney disease.

Functional MR imaging of kidney—novel approaches to monitoring renal physiology

infusion of hyperpolarized [ 13 C]urea under acute diuretic and antidiuresis conditions and observed upregulation of the urea transporter UT-A1 at the renal inner medulla under antidiuresis. This research reflects progress within the MRI community, and the radiology community in general, from what once was a primarily anatomic discipline to one that provides in vivo dynamic imaging of biological processes that have traditionally been studied in vitro, or analyzed in a very invasive fashion. With the advancement of instrumentation, pulse sequences, comprehension of MR biophysical mechanisms, and novel data analysis methods, MRI is able to provide a dynamic picture of tissue physiology, which includes tissue perfusion, tissue oxygenation, and oxygen metabolism (5, 14), water/solute transportation across cell membranes (4), tissue energetics (6), and more. For instance, based on the sensitivity of the MR signal to the blood oxygenation level (BOLD), the renal BOLD technique can provide a semiquantitative mapping of intrarenal oxygenation (10), thus opening new possibilities to study kidney diseases, particularly those related to tissue hypoxia (9). The quantitative BOLD (qBOLD) technique (5), originally developed for quantification of absolute blood oxygenation in neural applications, has the potential to obtain an absolute quantification of intrarenal oxygenation by separating the effect of blood oxygenation from the rest of hemodynamic parameters affecting renal BOLD signal (3). Since the major portion of kidney oxygen metabolism is used for active transportation of sodium, these BOLD-based techniques enable researchers and clinicians to noninvasively investigate important pathways regulating urine concentration. The intrarenal sodium gradient can also be directly quantified with sodiumMRI in both animal models and human subjects (2, 8). The kinetics of sodium gradient change are site specific and related to the loop diuretic mechanism in both intact and diseased kidneys. Other implementations of in vivo multinuclear magnetic resonance spectroscopy (MRS), including oxygen-17, fluorine19, phosphorus-31, and carbon-13, have been utilized to measure oxygen consumption, phosphate content and energy reserves, substrate selection, and rate of metabolic flux, respectively. However, compared with proton MRI, these multinuclear approaches usually suffer from extremely low intrinsic sensitivity, which results from low magnetogyric ratio, low natural abundance, and low in vivo concentration. At biological temperatures and field strengths that are attainable in a clinical setting, only a

NADPH oxidase inhibition reduces tubular sodium transport and improves kidney oxygenation in diabetes

Sustained hyperglycemia is associated with increased oxidative stress resulting in decreased intrarenal oxygen tension (Po(2)) due to increased oxygen consumption (Qo(2)). Chronic blockade of the main superoxide radicals producing system, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, normalizes Qo(2) by isolated proximal tubular cells (PTC) and reduces proteinuria in diabetes. The aim was to investigate the effects of acute NADPH oxidase inhibition on tubular Na(+) transport and kidney Po(2) in vivo. Glomerular filtration rate (GFR), renal blood flow (RBF), filtration fraction (FF), Na(+) excretion, fractional Li(+) excretion, and intrarenal Po(2) was measured in control and streptozotocin-diabetic rats during baseline and after acute NADPH oxidase inhibition using apocynin. The effects on tubular transporters were investigated using freshly isolated PTC. GFR was increased in diabetics compared with controls (2.2 ± 0.3 vs. 1.4 ± 0.1 ml·min(-1)·kidney(-1)). RBF was similar in both groups, resulting in increased FF in diabetics. Po(2) was reduced in cortex and medulla in diabetic kidneys compared with controls (34.4 ± 0.7 vs. 42.5 ± 1.2 mmHg and 15.7 ± 1.2 vs. 25.5 ± 2.3 mmHg, respectively). Na(+) excretion was increased in diabetics compared with controls (24.0 ± 4.7 vs. 9.0 ± 2.0 μm·min(-1)·kidney(-1)). In controls, all parameters were unaffected. However, apocynin increased Na(+) excretion (+112%) and decreased fractional lithium reabsorption (-10%) in diabetics, resulting in improved cortical (+14%) and medullary (+28%) Po(2). Qo(2) was higher in PTC isolated from diabetic rats compared with control. Apocynin, dimethylamiloride, and ouabain reduced Qo(2), but the effects of combining apocynin with either dimethylamiloride or ouabain were not additive. In conclusion, NADPH oxidase inhibition reduces tubular Na(+) transport and improves intrarenal Po(2) in diabetes.

Cellular adaptive changes in AKI: mitigating renal hypoxic injury

Hypoxia plays a role in ischemic, toxic and sepsis-induced acute kidney injury. Evolving hypoxia triggers renal adaptive responses that may mitigate the insult, leading to sublethal forms of cell injury. The unique capability of the kidney to downregulate oxygen consumption for tubular transport could represent one such adaptive response which promotes maintenance of renal oxygenation, thereby preserving cellular integrity. Tran et al. recently explored a novel mechanism that might prevent tubular damage by downregulation of mitochondrial biogenesis and oxygen consumption. Using expression profiling of kidney RNA in endotoxemic rodents and complementary studies in vitro and in PGC-1α knockout mice, they found a sepsis-related decline in PPARγ coactivator-1α (PGC-1α) expression and of PGC-1α-dependent genes involved in oxidative phosphorylation. This response may explain their observation of a paradoxical preservation of kidney oxygenation and structural integrity in sepsis, despite reduced renal blood flow and oxygen delivery. Thus, resetting of mitochondrial respiration and oxygen consumption during sepsis might be added to the growing list of adaptive responses that occur during hypoxic stress. This review will focus on these mechanisms that mitigate evolving hypoxic injury, even at the expense of transient renal dysfunction.

Variation in kidney oxygenation: towards long‐term recording by telemetry

Recently we developed a telemetry‐based carbon paste oxygen electrode (CPE) which can record kidney oxygenation in rats, unhindered by anesthesia or restraint. To test this new modality we first measured renal oxygen in anesthetised control and subtotaly nephrectomized (SNx) rats while varying inspired oxygen. Second, renal oxygen was measured before, during and after ischemia induced by a vascular clamp. Third, a fully implantable telemetry system was used for recording 3 weeks before and 1 day after ischemia. The CPE could easily detect changes in renal oxygen upon step‐wise increments and decrements of inspired oxygen, while renal perfusion pressure and blood flow remained unchanged from baseline. Kidney oxygenation was lower and less responsive to changes in inspired oxygen in SNx compared to controls. Telemetry‐based CPE could successfully measure renal oxygen before, during and after ischemia. Realisation of a telemetry‐based oxygen sensor, capable of long‐term monitoring of relevant perturbations, will enable us to elucidate links between renal oxygenation and kidney health. EU, FP7, Marie Curie Actions, International Outgoing Fellowship.

Telemetry‐based oxygen sensor to continuously monitor kidney oxygenation in conscious rats

Disturbed kidney oxygenation, i.e. renal hypoxia, may contribute to initiation and progression of both chronic kidney disease and acute kidney injury. A critical barrier to investigate this is lack of methods to chronically measure kidney tissue oxygen. We have developed a novel solution for chronic measurement of oxygen in the kidney. Using a telemetry‐based carbon paste oxygen electrode we continuously recorded kidney oxygenation for 6 weeks in rats, unhindered by anesthesia or restraint. Oxygen values were stable over time with a coefficient of variation (CV) within individual recordings of 16±6% and comparable values between animals; 90±27 μM oxygen. This was in agreement with recordings obtained under anaesthesia with spontaneous respiration; 85±19 μM oxygen and CV: 7±5%. In addition we observed a reproducible response to repeatedly applied changes in inspired oxygen, both in conscious and anesthetized rats. These experiments are the first to monitor renal oxygenation continuously in untethered conscious rats. EU, FP7, Marie Curie Actions, International Outgoing Fellowship.

Mammalian target of rapamycin regulate kidney oxygen consumption by controlling mitochondrial function via regulation of uncoupling protein 2

Excessive kidney oxygen consumption (QO2) without concomitantly increased delivery results in tissue hypoxia, which is a common pathway to the development of kidney disease, including diabetic nephropathy. Mammalian target of rapamycin (mTOR) regulates cell proliferation but also mitochondrial function. However, the role for kidney QO2 is presently unknown. We therefore investigated in vivo QO2 and also studied specific mechanisms using isolated mitochondria from control and diabetic rats.Control and streptozotocin‐diabetic rats were administered rapamycin (0.15 mg/day) for 14 days. Kidney function was measured under Inactin anesthesia.Inhibition of mTOR increased kidney QO2 (+121% and +31%) and decreased tubular transport efficiency (−50% and −36%) in both controls and diabetics without affecting glomerular filtration rate. mTOR inhibition increased QO2 of isolated mitochondria by inducing uncoupling via uncoupling protein‐2.In conclusion, mTOR inhibition increases kidney QO2 by inducing mitochondrial uncoupling, which may aggravate tissue hypoxia. Thus, mTOR inhibition in patients with pre‐existing nephropathy may accelerate the progression of disease.

The tubule pathology of septic acute kidney injury: a neglected area of research comes of age

Oxidant stress and compromised microcirculation underlie renal pathophysiology in septic acute kidney injury (AKI). Holthoff et al. report that resveratrol ameliorates these coupled abnormalities. They did not establish the primacy of either defect in septic AKI. However, tubule mitochondrial defects were recently reported to be involved in septic AKI pathogenesis, and resveratrol targets PGC-1α and respiratory enzymes. Together, these findings open new avenues for research into long-unresolved issues in the pathophysiology of septic AKI.

Prognostic value of intraoperative renal tissue oxygenation measurement on early renal transplant function

Ischemia time is a prognostic factor in renal transplantation for postoperative graft function and survival. Kidney transplants from living donors have a higher survival rate than deceased donor kidneys probably because of shorter ischemia time. We hypothesized that measurement of intraoperative kidney oxygenation (μHbO(2) ) and microvascular perfusion predicts postoperative graft function. We measured microvascular hemoglobin oxygen saturation by reflectance spectrophotometry and microcirculatory kidney perfusion by laser Doppler flowmetry 5 and 30min after kidney reperfusion on the organ surface in 53 renal transplant patients including 19 grafts from living donors. These values were related to systemic hemodynamics, cold ischemia time (cit), early postoperative graft function and length of hospital stay. μHbO(2) improved 30 min after reperfusion compared to 5 min (from 67% to 71%, P < 0.05). μHbO(2) correlated with mean arterial blood pressure and central venous pH (P < 0.01). Most importantly, μHbO(2) was significantly higher in kidneys from living compared with deceased donors (74% vs. 63%) and in kidneys without vs. with biopsy-proven postoperative rejection (71% vs. 45%, P < 0.001). Finally, μHbO(2) correlated positively with cit and postoperative creatinine clearance and negatively with postoperative plasma creatinine, need for hemodialysis and length of hospital stay. Our results suggest higher oxygen extraction and thus oxygen demand of the grafts shortly after reperfusion. The intraoperative measurement of tissue oxygenation in kidney transplants is predictive of early postoperative graft function. Future studies should evaluate the potential effect of intraoperative therapeutic maneuvers to improve organ tissue oxygenation in renal transplantation.

An implantable telemetry system for continuous chronic monitoring of kidney oxygenation in freely moving rats

We present a telemetry system for long-term monitoring of in-vivo kidney tissue oxygen. The transmitter contains an embedded potentiostat and has an attached carbon-paste electrode for amperometric detection of dissolved O2 (electrode diameter 200μm, transmitter wt 11 gm). Each electrode responds to physiological concentrations of O2 (50–80μM). The O</sub> concentration of the tissue is converted to an electrical current by the reduction of O2 on the carbon-paste. The total RMS noise of the telemetry system was 0.23μM. Inductive power transfer is utilised to recharge the telemeter transcutaneously, thus maintaining continuous recording for potentially the lifetime of the animal. In anesthetised rats the system was validated against a Clark-type electrode (50μm tip) and both electrodes were simultaneously inserted into the kidney. Rats were ventilated with different O2 concentrations to vary the kidney oxygen tension, and measurements were made at increasing depths in the tissue. The renal tissue oxygen tension measurements by these two methods were correlated (r2=0.466; p<0.001), with no fixed or proportional bias. Electrodes were also chronically implanted in the kidney. In conscious rats, the inspired O2 concentration was varied (10%, 21%, 100%). The observed renal oxygen tension agreed with changes in inspired O2 concentration. The implanted system was shown to be stable for >5 weeks.

NADPH oxidase inhibition reduces tubular Na+ transport and improves kidney oxygenation in diabetic rats

Sustained hyperglycemia is associated with increased oxidative stress and decreased renal oxygen tension (pO2) secondary to increased oxygen consumption. The NADPH oxidase is a major source of oxygen radicals in the kidney and we therefore studied the effects of NADPH oxidase inhibition (apocynin; APO) on tubular Na+ transport and kidney pO2 in diabetic rats. Glomerular filtration rate (GFR; inulin clearance), renal blood flow (RBF; transonic flow probe), proximal tubular electrolyte transport (Li+ clearance) and tissue pO2 (microelectrodes) were measured in Inactin-anesthetized control and streptozotocin-diabetic rats during baseline and after acute APO administration (10 mg/kg bolus). Diabetic rats had increased GFR (2.2±0.3 vs. 1.4±0.1 ml/min/kidney), reduced pO2 in cortex and medulla (34.6±0.9 & 15.7±1.2 vs. 41.6±1.9 & 26.1±2.3 mmHg), increased Na+ excretion (24.0±4.7 vs. 9.0±2.0 μm/h/kidney) and reduced Li+ excretion compared to controls (0.23±0.02 vs. 0.38±0.06). RBF was similar in both groups. In diabetics, APO increased Na+ (156%) and Li+ excretion (48%) and improved renal pO2 (21–35%), whereas GFR and RBF were unchanged. All parameters were unaffected by APO administered to control animals. Type-1 diabetic patients have increased risk to develop salt-sensitive hypertension, and our findings may provide a mechanistic explanation for this phenomenon.

A mathematical model of diffusional shunting of oxygen from arteries to veins in the kidney

To understand how arterial-to-venous (AV) oxygen shunting influences kidney oxygenation, a mathematical model of oxygen transport in the renal cortex was created. The model consists of a multiscale hierarchy of 11 countercurrent systems representing the various branch levels of the cortical vasculature. At each level, equations describing the reactive-advection-diffusion of oxygen are solved. Factors critical in renal oxygen transport incorporated into the model include the parallel geometry of arteries and veins and their respective sizes, variation in blood velocity in each vessel, oxygen transport (along the vessels, between the vessels and between vessel and parenchyma), nonlinear binding of oxygen to hemoglobin, and the consumption of oxygen by renal tissue. The model is calibrated using published measurements of cortical vascular geometry and microvascular Po(2). The model predicts that AV oxygen shunting is quantitatively significant and estimates how much kidney Vo(2) must change, in the face of altered renal blood flow, to maintain cortical tissue Po(2) at a stable level. It is demonstrated that oxygen shunting increases as renal Vo(2) or arterial Po(2) increases. Oxygen shunting also increases as renal blood flow is reduced within the physiological range or during mild hemodilution. In severe ischemia or anemia, or when kidney Vo(2) increases, AV oxygen shunting in proximal vascular elements may reduce the oxygen content of blood destined for the medullary circulation, thereby exacerbating the development of tissue hypoxia. That is, cortical ischemia could cause medullary hypoxia even when medullary perfusion is maintained. Cortical AV oxygen shunting limits the change in oxygen delivery to cortical tissue and stabilizes tissue Po(2) when arterial Po(2) changes, but renders the cortex and perhaps also the medulla susceptible to hypoxia when oxygen delivery falls or consumption increases.

MRI of renal oxygenation and function after normothermic ischemia–reperfusion injury

The in vivo assessment of renal damage after ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, is a major challenge. This injury often results in temporary or permanent nonfunction. In order to improve the clinical outcome of the kidneys, novel therapies are currently being developed that limit renal ischemia-reperfusion injury. However, to fully address their therapeutic potential, noninvasive imaging methods are required which allow the in vivo visualization of different renal compartments and the evaluation of kidney function. In this study, MRI was applied to study kidney oxygenation and function in a murine model of renal ischemia-reperfusion injury at 7 T. During ischemia, there was a strongly decreased oxygenation, as measured using blood oxygen level-dependent MRI, compared with the contralateral control, which persisted after reperfusion. Moreover, it was possible to visualize differences in oxygenation between the different functional regions of the injured kidney. Dynamic contrast-enhanced MRI revealed a significantly reduced renal function, comprising perfusion and filtration, at 24 h after reperfusion. In conclusion, MRI is suitable for the noninvasive evaluation of renal oxygenation and function. Blood oxygen level-dependent or dynamic contrast-enhanced MRI may allow the early detection of renal pathology in patients with ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, and consequently may lead to an earlier intervention or change of therapy to minimize kidney damage.

Renal protection in chronic kidney disease: hypoxia-inducible factor activation vs. angiotensin II blockade

The 5/6(th) nephrectomy or ablation/infarction (A/I) preparation has been used as a classic model of chronic kidney disease (CKD). We observed increased kidney oxygen consumption (Q(O2)) and altered renal hemodynamics in the A/I kidney that were normalized after combined angiotensin II (ANG II) blockade. Studies suggest hypoxia inducible factor as a protective influence in A/I. We induced hypoxia-inducible factor (HIF) and HIF target proteins by two different methods, cobalt chloride (CoCl(2)) and dimethyloxalyglycine (DMOG), for the first week after creation of A/I and compared the metabolic and renal hemodynamic outcomes to combined ANG II blockade. We also examined the HIF target proteins expressed by using Western blots and real-time PCR. Treatment with DMOG, CoCl(2), and ANG II blockade normalized kidney oxygen consumption factored by Na reabsorption and increased both renal blood flow and glomerular filtration rate. At 1 wk, CoCl(2) and DMOG increased kidney expression of HIF by Western blot. In the untreated A/I kidney, VEGF, heme oxygenase-1, and GLUT1 were all modestly increased. Both ANG II blockade and CoCl(2) therapy increased VEGF and GLUT1 but the cobalt markedly so. ANG II blockade decreased heme oxygenase-1 expression while CoCl(2) increased it. By real-time PCR, erythropoietin and GLUT1 were only increased by CoCl(2) therapy. Cell proliferation was modestly increased by ANG II blockade but markedly after cobalt therapy. Metabolic and hemodynamic abnormalities were corrected equally by ANG II blockade and HIF therapies. However, the molecular patterns differed significantly between ANG II blockade and cobalt therapy. HIF induction may prove to be protective in this model of CKD.

Structural antioxidant defense mechanisms in the mammalian and nonmammalian kidney: different solutions to the same problem?

Tissue oxygen levels are tightly regulated in all organs. This poses a challenge for the kidney, as its function requires blood flow, and thus, oxygen delivery to greatly exceed its metabolic requirements. Because superoxide production in the kidney is dependent on oxygen availability, tissue hyperoxia could drive oxidative stress. In the mammalian renal cortex, this problem may have been solved, in part, through a structural antioxidant defense mechanism. That is, arteries and veins are closely associated in a countercurrent arrangement, facilitating diffusional arterial-to-venous (AV) oxygen shunting. Because of this mechanism, a proportion of the oxygen delivered in the renal artery never reaches kidney tissue but instead diffuses to the closely associated renal veins, thus limiting oxygen transport to tissue. In the nonmammalian kidney, arteries and veins are not arranged in an intimate countercurrent fashion as in mammals; thus AV oxygen shunting is likely less important in regulation of kidney oxygenation in these species. Instead, the kidney's blood supply is predominately of venous origin. This likely has a similar impact on tissue oxygenation as AV oxygen shunting, of limiting delivery of oxygen to renal tissue. Thus, we hypothesize the evolution of structural antioxidant mechanisms that are anatomically divergent but functionally homologous in the mammalian and nonmammalian kidney.

Induction of HIF normalizes oxygen utilization and oxygenation in the diabetic kidney

Hyperglycemia results in increased oxygen consumption (QO2) and decreased oxygen tension (pO2) in the kidney. We hypothesize that activation of hypoxia‐inducible factors (HIF) protect against diabetes‐induced alterations in kidney function and oxygen metabolism.The experimental groups consisted of control and streptozotocin‐induced diabetic rats with and without chronic cobalt chloride (CoCl2; inducer of HIF; n=9–10/group).Diabetic rats had increased glomerular filtration rate (2.3±0.2 vs 1.5±0.2 ml/min/kidney; P&lt;0.05) and CoCl2 prevented this increase (1.5±0.1 ml/min/kidney). QO2 was increased in the diabetic kidney (23±2 vs 11±2 μmol/min/kidney; P&lt;0.05) and CoCl2 prevented this alteration (12±2 μmol/min/kidney). Tubular sodium transport (TNa)/QO2 was decreased in the diabetics (14±2 vs 33±8; P&lt;0.05), which was prevented by CoCl2 (25±4). Diabetic kidneys had reduced pO2 in both cortex and medulla compared to control (29±1 vs 45±2 and 22±1 vs 30±1 mmHg, respectively; both P&lt;0.05). CoCl2 prevented these decreases (cortex 42±1; medulla 39±1 mmHg). All investigated parameters were unaltered by CoCl2 in control rats.Diabetes‐induced alteration in kidney oxygen metabolism is prevented by HIF activation via two different mechanisms. Normalizing GFR, which reduces tubular electrolyte load, and maintaining TNa/QO2 contribute to normal QO2 and pO2 in the diabetic kidney. Early pharmacological activation of the HIF system may prevent the development of diabetic nephropathy. Funding: NIH/NIDDK DK077858 and Swedish Research Council.

Multiple mechanisms act to maintain kidney oxygenation during renal ischemia in anesthetized rabbits

We examined the mechanisms that maintain stable renal tissue PO(2) during moderate renal ischemia, when changes in renal oxygen delivery (DO(2)) and consumption (VO(2)) are mismatched. When renal artery pressure (RAP) was reduced progressively from 80 to 40 mmHg, VO(2) (-38 ± 7%) was reduced more than DO(2) (-26 ± 4%). Electrical stimulation of the renal nerves (RNS) reduced DO(2) (-49 ± 4% at 2 Hz) more than VO(2) (-30 ± 7% at 2 Hz). Renal arterial infusion of angiotensin II reduced DO(2) (-38 ± 3%) but not VO(2) (+10 ± 10%). Despite mismatched changes in DO(2) and VO(2), renal tissue PO(2) remained remarkably stable at ≥40 mmHg RAP, during RNS at ≤2 Hz, and during angiotensin II infusion. The ratio of sodium reabsorption to VO(2) was reduced by all three ischemic stimuli. None of the stimuli significantly altered the gradients in PCO(2) or pH across the kidney. Fractional oxygen extraction increased and renal venous PO(2) fell during 2-Hz RNS and angiotensin II infusion, but not when RAP was reduced to 40 mmHg. Thus reduced renal VO(2) can help prevent tissue hypoxia during mild renal ischemia, but when renal VO(2) is reduced less than DO(2), other mechanisms prevent a fall in renal PO(2). These mechanisms do not include increased efficiency of renal oxygen utilization for sodium reabsorption or reduced washout of carbon dioxide from the kidney, leading to increased oxygen extraction. However, increased oxygen extraction could be driven by altered countercurrent exchange of carbon dioxide and/or oxygen between renal arteries and veins.

Evaluation of kidney oxygen bioavailability in acute renal failure by blood oxygen level dependent magnetic resonance imaging

To assess the kidney oxygen bioavailability in acute renal failure using blood oxygen level dependent (BOLD) magnetic resonance (MR) imaging. Twenty-one patients with acute renal failure, including 18 patients with oliguric renal failure, 1 nonoliguric acute renal failure and 2 functional renal failure were enrolled in the study; 20 healthy subjects served as controls. All subjects received renal functional MR examination. BOLD MR imaging with 16 gradient-recalled-echoes on a 1.5-T scanner were performed. R2(*)(1/sec) values of the cortex and medulla and R2(*) ratio of the medulla to cortex (R2(*) ratio of M/C) of the renal were recorded respectively. The R2(*) values of the medulla was higher than those of the cortex in controls (17.64 +/-1.86/sec vs 13.73 +/-0.49/sec, P<0.00). The R2(*) ratio of M/C in controls was 1.28 +/-0.06. The R2(*) values of the medulla (13.31 +/-4.28/sec) and cortex (12.25 +/-2.41/sec) and the R2(* ) ratio of M/C (1.01 +/-0.25) in oliguric renal failure were lower than those in controls (P <0.05). Patients with functional renal failure and nonoliguric acute renal failure had higher R2(*) values in cortex and medulla and higher R2(*) ratio of M/C than those of controls. BOLD MRI demonstrates that decreased R2(*) values of cortex and medulla suggest lower oxygen bioavailability in acute renal failure and decreased R2(*)ratio of M/C suggests the disappearance of a steep cortico-medullary gradient of oxygen.

Local maximum oxygen disappearance rate has limited utility as a measure of local renal tissue oxygen consumption

Introduction: Methods for measurement of local oxygen consumption (VO 2) are required to allow development of treatments for kidney disease that target kidney oxygen dysregulation. In anaesthetized rabbits, we determined whether local oxygen disappearance rate (ODR) during complete renal ischaemia reflects tissue VO 2 in the kidney and in hindlimb skeletal muscle (biceps femoris). Methods: Whole kidney VO 2 was determined under conditions employed to alter oxygen consumption. The ureter was ligated to reduce VO 2 ( n = 6) or the mitochondrial uncoupler 2,4-dinitrophenol was administered to increase VO 2 ( n = 6). An additional 10 rabbits were studied which received neither treatment. Immediately following VO 2 measurements, oxygen partial pressure (PO 2) was measured, over the first 60 s after abrupt cardiac arrest, using fluorescence optodes and in a subset of experiments ( n = 6), Clark electrodes. Parallel experiments were performed in hindlimb skeletal muscle (biceps femoris). Results: ODR in the renal cortex and medulla, and in biceps femoris, was linear during the first ∼ 15 s after cardiac arrest ( r 2 ≈ 0.98). Using fluorescence optodes, maximum ODR averaged across all 22 rabbits in which the kidney was studied was − 0.75 ± 0.09 and − 0.60 ± 0.06 mm Hg/s respectively in the renal cortex and medulla. Maximum ODR averaged across all 10 rabbits in which the biceps femoris was studied was − 0.30 ± 0.06 mm Hg/s. ODR increased at greater initial PO 2 only in the renal cortex. ODR in neither the renal medulla nor biceps femoris varied with whole organ VO 2, although renal cortical ODR normalized for initial PO 2 was significantly correlated with whole organ VO 2 ( r 2 = 0.19). Maximum ODR obtained by Clark electrode was approximately four-fold greater than that obtained by fluorescence optode. Discussion: Because ODR correlates poorly with whole organ VO 2, it likely has limited utility as a measure of local VO 2.

Evaluation of Intrarenal Oxygenation by Blood Oxygen Level-Dependent Magnetic Resonance Imaging in Living Kidney Donors and Their Recipients: Preliminary Results

Objective Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) is a noninvasive tool to measure modifications in tissue oxygen content. Lower deoxyhemoglobin concentrations due to increased tissue oxygenation induce a longer transverse relaxation time (T2*), thus a stronger MRI signal. We have studied the changes in the kidney oxygenation profiles of living donors and their recipients by BOLD-MRI associated with transplantation and nephrectomy. Materials and Methods Two donor/recipient couples were selected for this preliminary study. BOLD-MRI was performed on the donor on the day prior to surgery, on day 4, and 1 month thereafter, and on the recipient on day 4 and 1 month postsurgery. Mean T2* values were measured in specific target regions in the cortical and medullary regions of each kidney using the T2StarMappingTool (Philips, Eindhoven, Netherlands). Modifications of tissue oxygen profiles were then compared considering the proportionality between T2* values and tissue oxygen content. Results The clinical courses posttransplantation were uneventful throughout the study; kidney function resumed rapidly. All MRI examinations showed a significantly higher T2* level in the cortex than in the medulla, confirming the notion that the medulla is hypoxic compared to the cortex. Nephrectomy and transplantation induced a significant rise in cortical T2* values in the remnant and transplanted kidney at day 4 and 1 month. Medullary T2* level only increased in the transplanted kidney. Conclusions Profound modifications in renal oxygenation intervene following transplantation and nephrectomy. BOLD-MRI may be a useful tool to explore these modifications and possibly identify pathological patterns.