Measurement Of Renal Blood Flow Research Articles

Abstract 640: RGS2 Deficiency Impairs Renal Hemodynamics and Function

Regulator of G protein signaling 2 (RGS2) regulates signaling by acting as a GTPase-activating protein for Gq/11α and Gi/oα subunits of heterotrimeric G proteins. Certain single nucleotide polymorphisms and loss-of-function mutations of RGS2 have been linked to human hypertension. RGS2 deficiency in the kidney is sufficient to cause hypertension in mice; however, the renal pathophysiological mechanisms are unknown. Here, we assessed renal hemodynamics and function using renal blood flow (RBF) and glomerular filtration rate (GFR) measurements, and assessment of pressure natriuresis in wild type (WT) and RGS2 null (RGS2-/-) mice. GFR was measured by plasma clearance of FITC-inulin. Pressure natriuresis was determined by increasing renal perfusion pressure (RPP) stepwise by clamping the superior mesenteric and celiac arteries, and abdominal aorta, while total RBF was simultaneously recorded with flow probe. Baseline GFR was markedly decreased in RGS2-/- mice compared to WT controls (1.8 ± 0.1 vs. 1.1 ± 0.1 ml/min/g kidney weight, p=0.004). Renal conductance was reduced (70 ± 9 vs. 51 ± 3 μl/min/g kidney weight, p=0.006) while renal vascular resistance (RVR; 14.9 ± 2.2 vs. 20.2 ± 1.3 mmHg/ml/min/g kidney weight, p=0.002) was elevated in RGS2-/- compared to WT mice. The absence of RGS2 resulted in decreased sensitivity and magnitude of change in RVR (WT: 11.17 ± 1.94 vs. RGS2-/-: 6.87 ± 0.90 mmHg/ml/min/g) and conductance (WT: -25.69 ± 3.22 vs. RGS2-/-: -13.87 ± 2.40 ml/min/mmHg/g) after a step increase in RPP. The acute pressure-natriuresis curve shifted rightward in RGS2-/- relative to WT, with no change in the slope. Fractional sodium excretion was unaffected by RGS2 deficiency. We conclude that RGS2 deficiency impairs renal function and autoregulation by increasing renal vascular resistance and reducing effective renal blood flow. The findings provide a new line of evidence for renal vascular dysfunction as a primary cause of hypertension. Mutations or downregulation of RGS2 in the kidney may contribute to human hypertension by causing renal hypoperfusion and decreased GFR. Signaling pathways regulated by RGS2 may provide therapeutic targets in hypertension patients harboring mutations that potentially decrease expression and/or function of RGS2.

Comparison of ASL and DCE MRI for the non-invasive measurement of renal blood flow: quantification and reproducibility

To investigate the reproducibility of arterial spin labelling (ASL) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and quantitatively compare these techniques for the measurement of renal blood flow (RBF). Sixteen healthy volunteers were examined on two different occasions. ASL was performed using a multi-TI FAIR labelling scheme with a segmented 3D-GRASE imaging module. DCE MRI was performed using a 3D-FLASH pulse sequence. A Bland-Altman analysis was used to assess repeatability of each technique, and determine the degree of correspondence between the two methods. The overall mean cortical renal blood flow (RBF) of the ASL group was 263 ± 41 ml min(-1) [100 ml tissue](-1), and using DCE MRI was 287 ± 70 ml min(-1) [100 ml tissue](-1). The group coefficient of variation (CVg) was 18 % for ASL and 28 % for DCE-MRI. Repeatability studies showed that ASL was more reproducible than DCE with CVgs of 16 % and 25 % for ASL and DCE respectively. Bland-Altman analysis comparing the two techniques showed a good agreement. The repeated measures analysis shows that the ASL technique has better reproducibility than DCE-MRI. Difference analysis shows no significant difference between the RBF values of the two techniques. Reliable non-invasive monitoring of renal blood flow is currently clinically unavailable. Renal arterial spin labelling MRI is robust and repeatable. Renal dynamic contrast-enhanced MRI is robust and repeatable. ASL blood flow values are similar to those obtained using DCE-MRI.

The renal arterial resistance index: a marker of renal function with an independent and incremental role in predicting heart failure progression

The renal arterial resistance index (RRI) is a measure of renal blood flow obtained by Doppler ultrasonography, which has been demonstrated to reflect both vascular and parenchymal renal abnormalities. The aim of the study was to evaluate clinical correlates and the prognostic relevance of RRI in a group of patients affected by chronic heart failure (CHF). We enrolled 250 CHF outpatients in a stable clinical condition and receiving conventional therapy. Peak systolic velocity and end-diastolic velocity of a segmental renal artery were obtained by pulsed Doppler flow. Then the RRI was calculated. Standard renal function assessment was obtained by the measurement of creatinine serum levels and the estimation of the glomerular filtration rate (GFR). During follow-up (21.4 ± 11.3 months), 41 patients experienced heart failure progression (hospitalization and/or heart transplantation and/or death due to worsening heart failure). Considered as a continuous variable, RRI was associated with events at univariate [hazard ratio (HR) 1.14; 95% confidence interval (CI) 1.09-1.19; P < 0.001] as well as at multivariate Cox regression analysis (HR 1.08; 95% CI 1.02-1.13; P = 0.004) after correction for independent predictors of the reference model. When the RRI was added to the reference model including GFR, a significant improvement of reclassification according to both category-free net reclassification improvement (NRI, 47%; 95% CI 13-80%; P = 0.006) and integrated discrimination improvement (IDI, 0.034; 95% CI 0.006-0.061; P = 0.016) was observed. Quantification of arterial renal perfusion provides a new parameter that independently predicts CHF patient outcome, thus strengthening its possible role in current clinical practice in order to better characterize renal function and stratify patients' prognosis.

Reproducibility of MRI renal artery blood flow and BOLD measurements in patients with chronic kidney disease and healthy controls

Determine the reproducibility of renal artery blood flow (RABF) and blood-oxygenation level dependent (R2 *) in patients with chronic kidney disease (CKD) and healthy controls. RABF and R2 * were measured in 11 CKD patients and 9 controls twice with 1- to 2-week interval. R2 * in the cortex and medulla were determined after breathing atmospheric air and 100% oxygen. Reproducibility was evaluated by coefficients of variation (CV), limits of agreements and intra-class coefficient calculated by variance components by maximum likelihood modeling. Single-kidney RABF (mL/min) for patients was: 170 ± 130 and 186 ± 137, and for controls: 365 ± 119 and 361 ± 107 (P < 0.05 versus patients), for first and second scans, respectively. RABF measurements were reproducible with a CV of 12.9% and 8.3% for patients and controls, respectively. Renal cortical R2 * was: 13.6 ± 0.9 and 13.5 ± 1.2 in patients (CV = 8.0%), and 13.8 ± 1.6 and 14.0 ± 1.5 in controls (CV = 5.6%), while medullary R2 *(s(-1) ) was: 26.9 ± 2.0 and 27.0 ± 4.0 (CV = 8.0%) in patients, and 26.0 ± 2.4 and 26.1 ± 2.1 (CV = 3.6%) in controls, for first and second scans, respectively. In both groups R2 * in medulla decreased after breathing 100% oxygen. The reproducibility was high for both RABF and R2 * in patients and controls, particularly in the cortex. Inhalation of 100% oxygen reduced medullary R2 *.

Quantitative assessment of acute kidney injury by noninvasive arterial spin labeling perfusion MRI: a pilot study

The kidneys are essential for maintaining homeostasis, are responsible for the reabsorption of water, glucose and amino acids, and filter the blood by removing waste. Acute kidney injury (AKI) is a syndrome characterized by the rapid loss of renal excretory function and the accumulation of end metabolic products of urea and creatinine. AKI is associated with the later development of chronic kidney disease and end-stage kidney disease, and may eventually be fatal. Early diagnosis of AKI and assessments of the effects of treatment, however, are challenging. The pathophysiological mechanism of AKI is thought to be the imbalance between oxygen supply and demand in the kidneys. We have assessed the ability of arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI), without the administration of contrast media, to quantify renal blood flow (RBF) non-invasively. We found that RBF was significantly lower in AKI patients than in healthy volunteers. These results suggest that ASL perfusion MRI, a noninvasive measurement of RBF, may be useful in the early diagnosis of AKI.

A New Device for Intraoperative Renal Blood Flow Measurement During Open‐Heart Surgery: An Experimental Study and the Clinical Pilot Study

Renal blood flow (RBF) may vary during cardiopulmonary bypass and low flow may cause insufficient blood supply of the kidney triggering renal failure postoperatively. Still, a valid intraoperative method of continuous RBF measurement is not available. A new catheter combining thermodilution and intravascular Doppler was developed, first calibrated in an in vitro model, and the catheter specific constant was determined. Then, application of the device was evaluated in a pilot study in an adult cardiovascular population. The data of the clinical pilot study revealed high correlation between the flow velocities detected by intravascular Doppler and the RBF measured by thermodilution (Pearson's correlation range: 0.78 to 0.97). In conclusion, the RBF can be measured excellently in real time using the new catheter, even under cardiopulmonary bypass.

High‐resolution mouse kidney perfusion imaging by pseudo‐continuous arterial spin labeling at 11.75T

Quantitative measure of blood flow provides important information regarding renal function, nephropathies and viability of kidney transplantation. Therefore, a method that would allow quantitative and reliable assessment of the renal microvascular perfusion would be very valuable. Arterial spin labeling Magnetic Resonance Imaging has started to be widely used for human studies. For rodents though, despite the increasing number of transgenic mouse models, renal perfusion Magnetic Resonance Imaging has been only sparsely reported. This study investigated the use of FAIR (flow-sensitive alternating inversion recovery) and pseudo-continuous arterial spin labeling (pCASL) for mouse renal blood flow measurements. FAIR and pCASL were compared in terms of sensitivity, absolute quantification, reproducibility and flexibility of implementation. Multislice and coronal imaging were also investigated. Studies were performed at 11.75 T with volumic transmitter/receiver radiofrequency coils and fast imaging. pCASL demonstrated better experimental flexibility and higher sensitivity compared to FAIR (> +20%). Renal blood flow values in the range of 550-750 mL/100 g/min for the cortex and of 140-230 mL/100 g/min for the medulla, consistent with literature data, were measured. pCASL was successfully applied at very high field for mouse renal blood flow measurements, demonstrating high sensitivity, flexibility and multislice imaging capability. pCASL may be considered as a method of choice for mouse kidney perfusion studies.

Detecting physiological systems with laser speckle perfusion imaging of the renal cortex

Laser speckle perfusion imaging (LSPI) has become an increasingly popular technique for monitoring vascular perfusion over a tissue surface. However, few studies have utilized the full range of spatial and temporal information generated by LSPI to monitor spatial properties of physiologically relevant dynamics. In this study, we extend the use of LSPI to analyze renal perfusion dynamics over a spatial surface of ~5 × 7 mm of renal cortex. We identify frequencies related to five physiological systems that induce temporal changes in renal vascular perfusion (cardiac flow pulse, respiratory-induced oscillations, baroreflex components, the myogenic response, and tubuloglomerular feedback) across the imaged surface and compare the results with those obtained from renal blood flow measurements. We find that dynamics supplied from global sources (cardiac, respiration, and baroreflex) present with the same frequency at all locations across the imaged surface, but the local renal autoregulation dynamics can be heterogeneous in their distribution across the surface. Moreover, transfer function analysis with forced blood pressure as the input yields the same information with laser speckle imaging or renal blood flow as the output during control, intrarenal infusion of N(ω)-nitro-L-arginine methyl ester to enhance renal autoregulation, and intrarenal infusion of the rho-kinase inhibitor Y-27632 to inhibit vasomotion. We conclude that LSPI measurements can be used to analyze local as well as global renal perfusion dynamics and to study the properties of physiological systems across the renal cortex.

Vascular smooth muscle function of renal glomerular and interlobar arteries predicts renal damage in rats

Previously, it was shown that individuals with good baseline (a priori) endothelial function in isolated (in vitro) renal arteries developed less renal damage after 5/6 nephrectomy (5/6Nx; Gschwend S, Buikema H, Navis G, Henning RH, de Zeeuw D, van Dokkum RP. J Am Soc Nephrol 13: 2909-2915, 2002). In this study, we investigated whether preexisting glomerular vascular integrity predicts subsequent renal damage after 5/6Nx, using in vivo intravital microscopy and in vitro myogenic constriction of small renal arteries. Moreover, we aimed to elucidate the role of renal ANG II type 1 receptor (AT1R) expression in this model. Anesthetized rats underwent intravital microscopy to visualize constriction to ANG II of glomerular afferent and efferent arterioles, with continuous measurement of blood pressure, heart rate, and renal blood flow. Thereafter, 5/6Nx was performed, interlobar arteries were isolated from the extirpated kidney, and myogenic constriction was assessed in a perfused vessel setup. Blood pressure and proteinuria were assessed weekly for 12 wk, and focal glomerulosclerosis (FGS) was determined at the end of study. Relative expression AT1R in the kidney cortex obtained at 5/6Nx was determined by PCR. Infusion of ANG II induced significant constriction of both afferent and efferent glomerular arterioles, which strongly positively correlated with proteinuria and FGS at 12 wk after 5/6Nx. Furthermore, in vitro measured myogenic constriction of small renal arteries negatively correlated with proteinuria 12 wk after 5/6Nx. Moreover, in vivo vascular reactivity negatively correlated with in vitro reactivity. Additionally, relative expression of AT1R positively correlated with responses of glomerular arterioles and with markers of renal damage. Both in vivo afferent and efferent responses to ANG II and in vitro myogenic constriction of small renal arteries in the healthy rat predict the severity of renal damage induced by 5/6Nx. This vascular responsiveness is highly dependent on AT1R expression. Intraorgan vascular integrity may provide a useful tool to guide the prevention and treatment of renal end-organ damage.

Hemodynamic Effects of Furosemide on Renal Perfusion as Evaluated by ASL-MRI

The aim of this study was to investigate the short-term effects of furosemide on renal perfusion by using arterial spin labeling (ASL) magnetic resonance imaging. Eleven healthy human subjects were enrolled in the study. The measurement of renal blood flow (RBF) was performed by applying an ASL technique with flow-sensitive alternating inversion recovery spin preparation and a single-shot fast spin-echo imaging strategy on a 3.0-T magnetic resonance scanner. For all subjects, the ASL magnetic resonance images were obtained before agent injection as a baseline scan. Then 20 mg of furosemide was injected intravenously. Postfurosemide ASL images were acquired following administration to evaluate the renal hemodynamic response. Postinjection scans showed that cortical RBF decreased from 366.59 ± 41.19 mL/100 g/min at baseline to 314.33 ± 48.83 mL/100 g/min at 10 minutes after the administration of furosemide (paired t test, P = .04 vs baseline), and medullary RBF decreased from 118.59 ± 24.69 mL/100 g/min at baseline to 97.38 ± 18.40 mL/100 g/min at 10 minutes after the administration of furosemide (paired t test, P = .01 vs baseline). There was a negative correlation between the furosemide-induced diuretic effect and the reduction of RBF (Spearman's r = -0.61). The dominant hemodynamic effect of furosemide on the kidney is associated with a decrease in both cortical and medullary blood perfusion. Furthermore, the quantitative ASL technique may provide an alternative way to noninvasively monitor the change in renal function due to furosemide administration.

P01.13: Renal blood flow measurements in normal pregnancies

P01.13: Renal blood flow measurements in normal pregnancies

Measurement of renal blood flow by phase-contrast magnetic resonance imaging during septic acute kidney injury

In septic patients, decreased renal perfusion is considered to play a major role in the pathogenesis of acute kidney injury. However, the accurate measurement of renal blood flow in such patients is problematic and invasive. We sought to overcome such obstacles by measuring renal blood flow in septic patients with acute kidney injury using cine phase-contrast magnetic resonance imaging. Pilot observational study. University-affiliated general adult intensive care unit. Ten adult patients with established septic acute kidney injury and 11 normal volunteers. Cine phase-contrast magnetic resonance imaging measurement of renal blood flow and cardiac output. The median age of the study patients was 62.5 yrs and eight were male. At the time of magnetic resonance imaging, eight patients were mechanically ventilated, nine were on continuous hemofiltration, and five required vasopressors. Cine phase-contrast magnetic resonance imaging examinations were carried out without complication. Median renal blood flow was 482 mL/min (range 335-1137) in septic acute kidney injury and 1260 mL/min (range 791-1750) in healthy controls (p = .003). Renal blood flow indexed to body surface area was 244 mL/min/m2 (range 165-662) in septic acute kidney injury and 525 mL/min/m2 (range 438-869) in controls (p = .004). In patients with septic acute kidney injury, median cardiac index was 3.5 L/min/m2 (range 1.6-8.7), and median renal fraction of cardiac output was only 7.1% (range 4.4-10.8). There was no rank correlation between renal blood flow index and creatinine clearance in patients with septic acute kidney injury (r = .26, p = .45). Cine phase-contrast magnetic resonance imaging can be used to noninvasively and safely assess renal perfusion during critical illness in man. Near-simultaneous accurate measurement of cardiac output enables organ blood flow to be assessed in the context of the global circulation. Renal blood flow seems consistently reduced as a fraction of cardiac output in established septic acute kidney injury. Cine phase-contrast magnetic resonance imaging may be a valuable tool to further investigate renal blood flow and the effects of therapies on renal blood flow in critical illness.

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.

Renal Perfusion 3-T MR Imaging: A Comparative Study of Arterial Spin Labeling and Dynamic Contrast-enhanced Techniques

To investigate the feasibility of and correlation between arterial spin-labeling (ASL) and dynamic contrast material-enhanced (DCE) 3-T magnetic resonance (MR) imaging in the measurement of renal blood flow (RBF). The review board approved this study. Nineteen healthy volunteers (seven women, 12 men; age range, 25-68 years) were recruited, and each provided written informed consent. MR imaging was performed with a 3-T whole-body system. Each subject underwent back-to-back ASL and DCE MR imaging. Ten runs of ASL imaging were performed by using the pseudocontinuous tagging scheme, and each run required an 18-second breath hold. For DCE imaging, a gadopentetate dimeglumine bolus (0.0125 mmol per kilogram of body weight) was administrated intravenously in all subjects except two; in the latter subjects, a 0.025 mmol/kg gadopentetate dimeglumine bolus was administered to evaluate the T1 saturation effect. RBF was quantified with both techniques and in both the cortex and the medulla. Agreement was evaluated for RBF measurements obtained with ASL imaging and those obtained with DCE imaging by using correlation analysis. RBF was apparently overestimated with 0.025 mmol/kg gadopentetate dimeglumine, which is a concentration that is commonly adopted for 1.5-T DCE. RBF was 227 mL/100 mL/min ± 30 (standard deviation) in the cortex and 101 mL/100 mL/min ± 21 in the medulla, as measured with ASL imaging, and 272 mL/100 mL/min ± 60 in the cortex and 122 mL/100 mL/min ± 30 in the medulla, as measured with DCE imaging. In the cortex, measurements obtained with ASL and DCE imaging exhibited a linear correlation (r = 0.66; statistical power, 0.8 at the 5% significance level) and fair agreement (intraclass correlation coefficient, 0.41). ASL and DCE 3-T MR imaging are feasible in the quantification of cortical renal perfusion, yielding measurements that are correlated but not entirely comparable. Intermodality differences have yet to be solved.

Feasibility of Measuring Renal Blood Flow Using Transesophageal Echocardiography in Pediatric Patients Undergoing Cardiac Surgery

To evaluate the feasibility of measuring renal blood flow (RBF) using transesophageal echocardiography (TEE) in pediatric patients undergoing cardiac surgery. A prospective noninterventional study. A university hospital. Twenty-three pediatric patients who underwent surgical repair for complex congenital heart defects were included in this study. None. The authors evaluated the accuracy of using TEE to visualize the left renal artery by comparing TEE images with preoperative computed tomography angiographic images. RBF was measured during the cardiopulmonary bypass (CPB) period. TEE images and Doppler studies from all subjects were interpreted by 2 blinded independent assessors. Inter- and intraobserver reproducibility was quantified by calculating the variability and intraclass correlation coefficients. Linear regression models were used to further investigate the relationship between volumetric RBF and CPB perfusion rate. The left renal artery was indentified successfully in 96% of the study population, with a mean Doppler angle of 19.5° ± 6.7° (all of them <30°). Both inter- and intraobserver variability was <10%. Inter- and intraobserver reproducibility in the RBF measurements were excellent. The volumetric RBF showed a linear relationship with the CPB perfusion rate (r = 0.881, p < 0.001) and the mean artery pressure (r = 0.457, p = 0.032). For 96% of pediatric patients undergoing cardiac surgery, it is feasible to measure RBF using intraoperative TEE during CPB. Volumetric RBF was related to the perfusion rate and the mean artery pressure during CPB.

Short-term effects of tolvaptan on renal function and volume in patients with autosomal dominant polycystic kidney disease

Tolvaptan and related V(2)-specific vasopressin receptor antagonists have been shown to delay disease progression in animal models of polycystic kidney disease. Slight elevations in serum creatinine, rapidly reversible after drug cessation, have been found in clinical trials involving tolvaptan. Here, we sought to clarify the potential renal mechanisms to see whether the antagonist effects were dependent on underlying renal function in 20 patients with autosomal dominant polycystic kidney disease (ADPKD) before and after 1 week of daily split-dose treatment. Tolvaptan induced aquaresis (excretion of solute-free water) and a significant reduction in glomerular filtration rate (GFR). The serum uric acid increased because of a decreased uric acid clearance, and the serum potassium fell, but there was no significant change in renal blood flow as measured by para-aminohippurate clearance or magnetic resonance imaging (MRI). No correlation was found between baseline GFR, measured by iothalmate clearance, and percent change in GFR induced by tolvaptan. Blinded post hoc analysis of renal MRIs showed that tolvaptan significantly reduced total kidney volume by 3.1% and individual cyst volume by 1.6%. Preliminary analysis of this small cohort suggested that these effects were more noticeable in patients with preserved renal function and with larger cysts. No correlation was found between changes of total kidney volume and body weight or estimated body water. Thus, functional and structural effects of tolvaptan on patients with ADPKD are likely due to inhibition of V(2)-driven adenosine cyclic 3',5'-monophosphate generation and its aquaretic, hemodynamic, and anti-secretory actions.

Positron Emission Tomography (PET) Assessment of Renal Perfusion

Positron emission tomography (PET) is a radionuclide imaging technique that allows noninvasive mapping of radiopharmaceutical concentrations in three-dimensional space. PET methods have been described for imaging and quantification of renal perfusion using cyclotron-produced (15)O-water and (13)N-ammonia, as well as using generator-produced (82)RbCl and (62)Cu-ETS. Although the majority of clinical PET facilities will lack the in-house biomedical cyclotron needed for (15)O and (13)N production, the generator-produced tracers are available to virtually any clinical site with a PET camera. Studies with these radiopharmaceuticals have largely focused on methodologic issues, and agent validation for renal blood flow measurements. However, the resulting PET methods for quantification of renal perfusion do appear suitable for application to both research and clinical problems in renal pathophysiology.

Acute mineralocorticoid receptor blockade produces rapid renal vasodilation with no impairment of autoregulation in vivo

Chronic blockade of the mineralocorticoid receptor (MR) significantly attenuates obesity‐induced rise in mean arterial pressure (MAP), sodium reabsorption and glomerular filtration rate (GFR). The mechanisms and immediate time‐course underlying these responses are not known but may involve rapid, non‐genomic actions of aldosterone at the MR. We determined the immediate renal hemodynamic response to MR blockade in anesthetized Sprague‐Dawley rats instrumented for measurement of MAP and renal blood flow (RBF). Animals were infused with the MR antagonist potassium canrenoate (20mg/kg i.v) or saline. Within 1 min of MR blockade, MAP fell (−9.1±3.6 mmHg, n=5, p&lt;0.001) which was absent in saline controls (−0.4±1.6 mmHg, n=4). RBF rose (0.3±0.1 mL/min, n=5, p&lt;0.001) with no change with saline alone (−0.1±0.1 mL/min, n=4). Renal arterial conductance (RBF/MAP) rose only with MR blockade (0.01±0.003 mLmin−1 · mmHg−1, n=5, p&lt;0.001; saline −0.0003±0.001 mLmin−1 · mmHg−1, n=4) reflecting renal vasodilatation. Autoregulatory index was comparable in both groups (canrenoate 0.34±0.2 vs saline 0.21±0.1). We demonstrate rapid renal vasodilation in response to MR blockade in vivo suggesting differences between acute and chronic modulation of renal hemodynamics by aldosterone. NIH HL51972, CIHR

Erythropoietin does not attenuate renal dysfunction or inflammation in a porcine model of endotoxemia

Erythropoietin (EPO) is a multifunctional cytokine with anti-apoptotic, anti-inflammatory, and organ protective effects. EPO protects against ischemia-reperfusion injuries, and recent reports suggest that EPO also prevents organ dysfunction in experimental sepsis. The aims of this study were to determine whether EPO prevents endotoxemia-induced organ dysfunction in a porcine model and to characterize the immunomodulatory and anti-apoptotic effects of EPO. Twenty-eight pigs were randomly assigned to three groups: (1) endotoxemia treated with EPO 5000 IU/kg, (2) endotoxemia treated with placebo, and (3) a sham group anesthetized and submitted to sham operation without treatment. A laparotomy was performed, and a flow probe was placed around the left renal artery, which allowed renal blood flow (RBF) measurements. Endotoxemia was induced by an infusion of lipopolysaccharide. After 2 h, the infusion was reduced to a maintenance dose and the animals were fluid resuscitated. The glomerular filtration rate (GFR), RBF, renal oxygen consumption, and plasma cytokines [interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha] were analyzed. Renal biopsies were analyzed for cytokine content and apoptosis. Endotoxemia elicited impaired renal function, estimated as GFR, and increased the levels of renal apoptotic cells, with no modifying effect of EPO. Furthermore, EPO had no effect on RBF, renal oxygen consumption, or the systemic hemodynamic response to endotoxemia. EPO did not modify the inflammatory response, measured as changes in cytokine levels in plasma and organs. EPO did not confer renal protection in this fluid-resuscitated porcine model of endotoxemia, and EPO did not modify the inflammatory response.

Dependence of Renal Blood Flow on Renal Artery Stenosis Measured Using CT Angiography

The present study investigates the suitability of computed tomography angiography (CTA) depicting the degree of renal artery stenosis for estimating renal blood flow (RBF) in a kidney. We investigated renal artery stenosis assessment by CTA in eight adult female hybrid pigs with an ultrasound probe implanted at the renal vein for RBF measurement. An inflatable metal-free cuff was placed around the renal artery to control the RBF. The RBF was then reduced in four steps. For each reduced RBF value and baseline RBF, CTA with a reconstructed slice thickness of 0.625 mm was performed in the arterial phase following injection of 80 ml of nonionic intravenous contrast medium. The radius of the stenotic and non-stenotic renal artery segment was measured in the reconstructed images. A significant linear correlation (p < 0.0001) was found between the relative apparent stenosis (calculated as the ratio of the radii of the actual stenotic segment and a non-stenotic renal artery segment) and RBF. The linear regression yielded a slope of 0.57 and a y-axis of 24.1 %. A significant linear correlation (p < 0.0001) was also found between the relative true stenosis (the ratio of the radii of the actual stenotic segment and a non-stenotic renal artery segment at baseline) and the RBF. The linear regression yielded a slope of 0.67 and a y-axis of 13.8 %. The results show that the relative stenosis apparent on CTA differs from the true degree of renal artery stenosis. Nevertheless, the degree of renal artery stenosis determined by CTA provides a reliable estimate of the resulting RBF reduction.