Changes In Renal Perfusion Research Articles

Hemodynamic management of acute kidney injury

Purpose of review To discuss the role of hemodynamic management in critically ill patients with acute kidney injury. Recent findings Acute kidney injury (AKI) may be associated with persistent alterations in renal perfusion, even when cardiac output and blood pressure are preserved. The effects of interventions aiming at increasing renal perfusion are best evaluated by renal Doppler or contrast enhance ultrasound. However, limited data have been acquired with these techniques and the essential of the literature is based on surrogates of renal function such as incidence of use of renal replacement therapy. Fluids may increase renal perfusion but their effects are quite unpredictable and can be dissociated from their impact on cardiac output and arterial pressure. Inotropes can also be used in selected conditions. At the de-escalation phase, fluid withdrawal should be considered. Safe fluid withdrawal may be achieved when applied in selected patients with preserved tissue perfusion presenting signs of fluid intolerance. When applied, stopping rules should be set. Dobutamine, milrinone and levosimendan increase renal perfusion in AKI associated with cardiac failure or after cardiac surgery. However, the impact of these agents in sepsis is not well defined. Regarding vasopressors, norepinephrine is the first-line vasopressor agent, but vasopressin derivative may limit the requirement of renal replacement therapy. Angiotensin has promising effects in a limited size post-Hoc analysis of a RCT, but these data need to be confirmed. While correction of severe hypotension is associated with improved renal perfusion and function, the optimal mean arterial pressure (MAP) target level remains undefined, Systematic increase in MAP results in variable changes in renal perfusion. It sounds reasonable to individualize MAP target, paying attention to central venous and intraabdominal pressures, as well as to the response to an increase in MAP. Summary Recent studies have refined the impact of the various hemodynamic interventions on renal perfusion and function in critically ill patients with AKI. Though several of these interventions improve renal perfusion, their impact on renal function is more variable.

Patient-specific computational flow simulation reveals significant differences in paravisceral aortic hemodynamics between fenestrated and branched endovascular aneurysm repair

BackgroundEndovascular aneurysm repair with four-vessel fenestrated endovascular aneurysm repair (fEVAR) or branched endovascular aneurysm repair (bEVAR) currently represent the forefront of minimally invasive complex aortic aneurysm repair. This study sought to use patient-specific computational flow simulation (CFS) to assess differences in postoperative hemodynamic effects associated with fEVAR vs bEVAR. MethodsPatients from two institutions who underwent four-vessel fEVAR with the Cook Zenith Fenestrated platform and bEVAR with the Jotec E-xtra Design platform were retrospectively selected. Patients in both cohorts were treated for paravisceral and extent II, II, and V thoracoabdominal aortic aneurysms. Three-dimensional finite element volume meshes were created from preoperative and postoperative computed tomography scans. Boundary conditions were adjusted for body surface area, heart rate, and blood pressure. Pulsatile flow simulations were performed with equivalent boundary conditions between preoperative and postoperative states. Postoperative changes in hemodynamic parameters were compared between the fEVAR and bEVAR groups. ResultsPatient-specific CFS was performed on 20 patients (10 bEVAR, 10 fEVAR) with a total of 80 target vessels (40 renal, 20 celiac, 20 superior mesenteric artery stents). bEVAR was associated with a decrease in renal artery peak flow rate (−5.2% vs +2.0%; P < .0001) and peak pressure (−3.4 vs +0.1%; P < .0001) compared with fEVAR. Almost all renal arteries treated with bEVAR had a reduction in renal artery perfusion (n = 19 [95%]), compared with 35% (n = 7) treated with fEVAR. There were no significant differences in celiac or superior mesenteric artery perfusion metrics (P = .10-.27) between groups. Time-averaged wall shear stress in the paravisceral aorta and branches also varied significantly depending on endograft configuration, with bEVAR associated with large postoperative increases in renal artery (+47.5 vs +13.5%; P = .002) and aortic time-averaged wall shear stress (+200.1% vs −31.3%; P = .001) compared with fEVAR. Streamline analysis revealed areas of hemodynamic abnormalities associated with branched renal grafts which adopt a U-shaped geometry, which may explain the observed differences in postoperative changes in renal perfusion between bEVAR and fEVAR. ConclusionsbEVAR may be associated with subtle decreases in renal perfusion and a large increase in aortic wall shear stress compared with fEVAR. CFS is a novel tool for quantifying and visualizing the unique patient-specific hemodynamic effect of different complex EVAR strategies. Clinical RelevanceThis study used patient-specific CFS to compare postoperative hemodynamic effects of four-vessel fenestrated endovascular aneurysm repair (fEVAR) and branched endovascular aneurysm repair (bEVAR) in patients with complex aortic aneurysms. The findings indicate that bEVAR may result in subtle reductions in renal artery perfusion and a significant increase in aortic wall shear stress compared with fEVAR. These differences are clinically relevant, providing insights for clinicians choosing between these approaches. Understanding the patient-specific hemodynamic effects of complex EVAR strategies, as revealed by CFS, can aid in future personalized treatment decisions, and potentially reduce postoperative complications in aortic aneurysm repair.

Spectral computed tomography parameters could be surrogate imaging markers to detect early perfusion changes in diabetic kidneys.

Kidney microvasculopathy is the baseline pathophysiological feature of diabetic kidney disease (DKD). We aimed to evaluate the spectral computed tomography (CT) parameters for detecting renal perfusion changes among diabetic patients. From August 2020 to June 2022, 34 patients (age, 57.7±10.7 years; male, 20) clinically diagnosed with type 2 diabetes mellitus (DM) and 19 DM-free individuals (age, 48.1±16.9 years; male, 12) were selected for analysis. The series participants formed the DM group and control group, respectively. Spectral parameters, including effective atomic number (Zeff), iodine density (ID), normalized iodine density (NID) and the slope of the energy spectrum curves (λ), between the 2 groups were analyzed using independent samples t-test. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic performance of spectral parameters for detecting renal perfusion changes. The results indicate that in both cortical and medullary phases, the values of Zeff, ID, NID, and λ40-70 for the renal cortex of the DM group were significantly higher than those in the control group (P<0.05). In the cortex phase, the diagnostic efficacy of cortical spectral CT parameters discriminating DM patients from controls was as follows: the area under ROC curve (AUC) of ID value was 0.816 [95% confidence interval (CI): 0.679-0.921] at the optimal cutoff value 4.14, the AUC of Zeff value was 0.800 (95% CI: 0.668-0.901) at the optimal cutoff value 9.26, the AUC of λ40-70 value was 0.822 (95% CI: 0.675-0.918) at the optimal cutoff value 8.26, and the AUC of NID value was 0.851 (95% CI: 0.684-0.926) at the optimal cutoff value 0.37. In medullary phase: the AUC of ID value was 0.769 (95% CI: 0.617-0.846) at the optimal cutoff value 5.08, the AUC of Zeff value was 0.763 (95% CI: 0.614-0.837) at the optimal cutoff value 9.58, the AUC of λ40-70 value was 0.766 (95% CI: 0.617-0.839) at the optimal cutoff value 10.07, and the AUC of NID value was 0.79 (95% CI: 0.623-0.855) at the optimal cutoff value 1.37. Spectral CT could serve as an alternative protocol for the early identification of kidney injury in diabetic patients.

Renal perfusion improvement in the perioperative period after unilateral endovascular revascularization in patients with atherosclerotic renal artery stenosis.

The clinical benefits of endovascular treatment in renal artery stenosis (RAS) remain controversial. This study used an intraoperative renal perfusion imaging technique, called flat-panel detector parenchymal blood volume imaging (FD-PBV), to observe the change in renal perfusion after endovascular treatment in RAS. In a prospective, single-center study, we assigned 30 patients with atherosclerotic RAS who underwent endovascular treatment between March 2016 and March 2021. The preoperative and postoperative results of renal perfusion, blood pressure, and renal function, were compared. Both median kidney volume (p < 0.001) and median preoperative mean density of contrast medium (MDCM) (p = 0.028) increased significantly after endovascular treatment. The ratio of postoperative and preoperative MDCM differed greatly among the patients. For patients with preoperative MDCM <304.0 HU (Subgroup A, 15 cases), MDCM significantly increased after treatment (p = 0.001) and 12 (80.0%) patients had more than 10% increase in renal perfusion. For patients who had relatively high preoperative renal perfusion (MDCM ≥304.0 HU, Subgroup B, 15 cases), preoperative and postoperative MDCM were similar (p = 0.776). On the other hand, the serum creatinine levels significantly decreased in Subgroup A (p = 0.033) and fewer antihypertensive drugs were used after endovascular revascularization (p = 0.041). The preoperative and postoperative creatinine levels and number of antihypertensive drugs were similar in Subgroup B. During the perioperative period, RAS patients with relatively low preoperative renal perfusion levels had greater improvement in renal perfusion, renal function, and blood pressure control after endovascular treatment. The improvement of renal function needs to be confirmed by long-term follow-up.

Influence of hyperthermic intraperitoneal chemotherapy on renal blood perfusion

PurposeHyperthermic intraperitoneal chemotherapy (HIPEC) is accompanied with an increased risk of acute kidney injury (AKI). Whether AKI is induced by chemotoxicity or hyperthermia-related changes in renal perfusion remains controversial. The influence of HIPEC on renal perfusion has not been evaluated in patients yet.MethodsRenal blood perfusion was assessed in ten patients treated with HIPEC by intraoperative renal Doppler pulse-wave ultrasound. Ultrasound (US) examinations were performed pre-, intra-, and postoperative with analyses of time-velocity curves. Patient demographics, surgical details, and data regarding renal function were recorded perioperatively. For evaluation of renal Doppler US to predict AKI, patients were divided in two groups with (AKI +) and without (AKI −) kidney injury.ResultsThroughout HIPEC perfusion, neither significant nor consistent changes in renal perfusion could be observed. Postoperative AKI occurred in 6 of 10 participating patients. Intraoperative renal resistive index (RRI) values > 0.8 were observed in one patient developing stage 3 AKI according KDIGO criteria. At 30 min in perfusion, RRI values were significantly higher in AKI + patients.ConclusionAKI is a common and frequent complication after HIPEC, but underlying pathophysiology remains elusive. High intraoperative RRI values may indicate an increased risk of postoperative AKI. Present data challenges the relevance of hyperthermia-derived hypothesis of renal hypoperfusion with prerenal injury during HIPEC. More attention should be drawn towards chemotoxic-induced hypothesis of HIPEC-induced AKI and caution applying regimens containing nephrotoxic agents in patients. Further confirmatory and complementary studies on renal perfusion as well as pharmacokinetic HIPEC studies are required.

Effects of stone density on alteration in renal resistive index after extracorporeal shock wave lithotripsy for non-obstructed kidney stones

Aim: The doppler-based renal resistive index is a recently proposed technique for measuring changes in renal perfusion and predicting acute kidney damage. The purpose of this study was to look at the influence of stone density on the renal resistive index (RI) after extracorporeal shock wave lithotripsy (ESWL) in patients with non-obstructed kidney stones.Material and Method: Between May 2020 and July 2021, 48 consecutive patients with unilateral renal calculi of ≤ 20 mm were treated with ESWL monotherapy. The patients' non-contrast computed tomography (NCCT) images were processed and grouped into two groups using Hounsfield units (HU) (Group 1, n=27, ≤ 1000 HU; Group 2, n=21, &amp;gt; 1000 HU). The same radiologist performed Doppler ultrasonography on all cases before, one hour, and one week following ESWL. Measurement of the RI taken in the remote region (at least 20 mm from the stones). Patient age, gender, BMI, stone laterality, stone size, and stone position were investigated as potential predictors.Results: The average stone size for Group 1 was 11.7±3.3 mm and 12.1±2.8 mm for Group 2. The mean RI values before ESWL for Group 1 and Group 2 were 0.54 and 0.53, respectively. On comparing the pre-treatment data with the 1 hour after ESWL, a statistically significant increase was recorded in the RI value for both groups. However, there was no significant difference in RI values between groups 1 and 2 1 hour and 1 week following lithotripsy therapy. After one week, the mean RI returned to pretreatment levels, according to a follow-up doppler investigation. There was no association between stone density and RI (p &amp;gt; 0.05). Conclusion: High stone densities detected with NCCT were not associated with a significant change in RI. Post-ESWL therapy alterations are present and reversible one week after the treatment.

Acute Effects of Insulin Infusion on Kidney Hemodynamic Function in People With Type 2 Diabetes and Normal Kidney Function

Acute Effects of Insulin Infusion on Kidney Hemodynamic Function in People With Type 2 Diabetes and Normal Kidney Function

Multiple Spontaneous Remitting and Relapsing Nephrotic Syndrome in a Cirrhotic Patient

Reports of spontaneous remissions in minimal change disease are rare and often associated with secondary causes. We report the case of a 47-year-old male patient with HIV-HBV/HDV co-infection and cirrhosis, admitted in the emergency department with nephrotic syndrome (hypoalbuminemia 1.2 g/dL and nephrotic range proteinuria 14 440 mg/g of creatinine). Ultrasound showed normal kidneys. Viral load for HIV, HBV, HDV and anti-HCV were negative. Immunologic and dysproteinemia study was normal and there were no signs of malignancy on body computer tomography scan. Abdominal fat pad biopsy was Congo red-stain negative. After initiating an angiotensin-converting enzyme inhibitor, the proteinuria decreased to 3891 mg/g. A kidney biopsy was scheduled, but the patient abandoned follow-up. Two years later, he presented again in anasarca, with mild elevation of transaminases, severe hypoalbuminemia (0.7 g/dL), acute kidney injury (creatinine 2.7 mg/dL) and heavy proteinuria (37 g/24 h). One month after the onset, when referred to a nephrologist, he was in complete remission. A year later, he presented a third episode of abrupt onset nephrotic syndrome. Kidney biopsy revealed minimal change disease. Corticosteroid therapy was withheld, and after one month the patient was again in complete remission. We hypothesize that, in the context of cirrhosis, the clearance of a putative permeability circulating factor may be diminished; hemodynamic changes in renal perfusion in decompensated chronic liver disease may interfere in the glomerular barrier function; and a genetic polymorphism related to podocyte dysfunction could precipitate a nephrotic syndrome that resolves once the liver function resumes its steady state. This case represents an unprecedented report of a minimal change disease in a cirrhotic patient, presenting with recurring episodes of nephrotic syndrome followed by early spontaneous remission.

Quantitative Analysis of Renal Perfusion in Rhabdomyolysis-Induced Acute Kidney Injury Using Contrast-Enhanced Ultrasound: An Experimental Study.

The aim of this study was to evaluate renal perfusion changes in rats with acute kidney injury induced by rhabdomyolysis, using quantitative parameters obtained with contrast-enhanced ultrasound (CEUS). Sprague-Dawley (SD) rats were randomly divided into an experimental group (n=40) and a control group (n=20). Each group was further divided into four subgroups (0.5-, 6-, 24- and 72-h groups). Time-intensity curves and related quantitative parameters of the renal cortex and medulla were obtained by CEUS, and the contrast characteristics analyzed for different time points. In the experimental group, the CEUS quantitative parameters for the renal medulla of time to peak (TTP), descending time/2 (DT/2) and area under the curve (AUC) increased, whereas ascending slope (AS) and descending slope (DS) decreased. Similarly, renal cortical AS, DS and AUC in the experimental group differed significantly from those in the control group. With respect to the CEUS quantitative parameters for the renal cortex, AUC increased, and AS and DS decreased. These parameters differed significantly between the experimental and control groups. CEUS is sensitive to change in renal perfusion in rhabdomyolysis-induced acute kidney injury and, thus, has diagnostic value.

Ultrasonographic assessment of renal perfusion in bitches with mammary carcinoma treated with long-term carprofen

The aim of this study was to evaluate renal hemodynamics, routine clinical and laboratory parameters used to estimate renal function, and clinical evolution during six months in bitches with mammary carcinomas that underwent mastectomy and were treated (TG) or not (CG) with carprofen for three months after surgery. Twenty-six bitches with mammary carcinoma were equally distributed into TG that received carprofen 4.4 mg/kg/day for 90 days and CG that did not receive anti-inflammatory medication. Renal artery Doppler flowmetry, contrast-enhanced ultrasound (CEUS) of renal parenchyma, haematological, biochemical and clinical analyses were obtained once a month. These data were compared between groups and time via analysis of variance (ANOVA) in a completely randomized design with repeated measures (P < 0.05). On B-mode ultrasound, the area of the renal artery was greater (P = 0.0003) in the TG. Regarding laboratory findings, haematocrit and haemoglobin were similar in both groups, showing a significant and gradual increase after three months of treatment; MCV, MHC, and MCHC were increased (P < 0.05) and lymphocyte and band counts decreased (P < 0.05) in the TG. Regarding biochemical tests, ALT was the only parameter with a significant difference, being higher (P = 0.0272) in the treated group. It can be concluded that the use of carprofen for 90 days causes minimal changes in renal perfusion, erythrocyte parameters and ALT activity, and reduces the proportion of blood inflammatory cells. Therefore, use of this medication can be carried out safely in patients who require auxiliary cancer treatment.

MO336RENAL CONTRAST-ENHANCED ULTRASOUND (CEUS) TO EVALUATE EARLY AND CHRONIC MODIFICATIONS OF RENAL PERFUSION AND TO PREDICT RENAL DYSFUNCTION AFTER RENAL ISCHEMIA-REPERFUSION IN MICE

Abstract Background and Aims Renal ischemia-reperfusion can lead to acute kidney injury (AKI), increasing the risk of developing chronic kidney disease (CKD) through inflammation and vascular lesions. Serum urea or creatinine level routinely used as diagnostic indices of renal function are always delayed from the onset of the disease. Therefore, we currently lack reliable markers to early detect AKI, especially in animals. We aimed to show that non-invasive renal contrast-enhanced ultrasound (CEUS) could be a reliable tool to assess early and chronic changes of renal perfusion after renal ischemia-reperfusion. Method Male C57BL6 mice underwent 15 minutes of unilateral renal ischemia by clamping of the left renal vascular pedicle (n = 7), or a sham procedure (n = 3), under inhaled general anesthesia by Sevoflurane. A renal ultrasound was performed on the left ischemic kidney at baseline 1 week before the surgery, then, 20 minutes after reperfusion to assess early modifications of renal perfusion, and 1 month after reperfusion to follow chronic modifications. CEUS was performed in supine position by using a high-resolution ultrasonic imaging system (VEVO 3100 Fujifilm Visualsonics, Toronto, Canada) with a MX550D probe fixed in place with an iron support, ensuring the constant imaging plane throughout acquisition. First, a continuous infusion of microbubbles (VS-11913, Fujifilm Visualsonics, Toronto, Canada) was done through the tail vein, then a high mechanical index burst was given to destroy microbubbles when the contrast enhancement had reached a steady state, and finally, low mechanical-index imaging mode was used until, and 30 sec after the contrast agent concentration reached the plateau. Images were recorded and were analyzed using the “destruction-replenishment” fitting model of the Vevo LAB software (Fujifilm Visualsonics, Toronto, Canada). Renal perfusion was estimated by the total renal Blood Volume (rBV) parameter and was expressed as percentage of the baseline value for each animal. Renal function was also assessed by serum urea concentration 1 month after reperfusion, and the long axis lengths of both the kidneys were measured ex vivo after the mice were euthanized. Results Renal perfusion of the ischemic kidney measured by CEUS was significantly decreased as soon as 20 minutes of reperfusion compared to baseline (median 28,8% of baseline value; interquartiles [20,1 – 69,8%]). 1 month after reperfusion, renal perfusion recovered partially but was still significantly decreased compared to baseline (median 79,9% of baseline value; interquartiles [52,8 – 99,9%]) (Figure A). In sham operated mice, renal perfusion did not differ from baseline at 20 minutes or 1 month (p &amp;gt; 0.05). The renal function, assessed by serum urea, was mildly but significantly impaired 1 month after ischemia-reperfusion compared with sham (median serum urea 9,8 vs. 7,6 mmol/L) (p = 0.02), and this was consistent with the observed kidney atrophy in the ischemic group when compared to the contralateral kidney (median long axis length 7,5 vs 10,8 mm) (p = 0.03). Moreover, the decrease of renal perfusion 20 minutes after reperfusion was significantly correlated with the impairment of renal perfusion 1 month after reperfusion (Pearson r = 0.836, p = 0.005) and with the serum urea level at 1 month (Pearson r = -0.710, p = 0.03) (Figure B-C). Conclusion Renal CEUS was able to detect early impairment of renal perfusion as soon as 20 minutes after 15 minutes of renal ischemia in mice, and perfusion was still decreased 1 month after reperfusion, compared to baseline. This early impairment of perfusion was correlated with the chronic decrease of renal perfusion and renal function 1 month after reperfusion. This was also associated with a significant kidney atrophy. CEUS is an interesting non-invasive tool to assess renal lesions dynamically after ischemia-reperfusion.

Application of dynamic contrast enhanced ultrasound in the assessment of kidney diseases.

Many forms of acute and chronic disease are linked to changes in renal blood flow, perfusion, vascular density and hypoxia, but there are no readily available methods to assess these parameters in clinical practice. Dynamic contrast enhanced ultrasound (DCE-US) is a method that provides quantitative assessments of organ perfusion without ionising radiation or risk of nephrotoxicity. It can be performed at the bedside and is suitable for repeated measurements. The purpose of this review is to provide updates from recent publications on the utility of DCE-US in the diagnosis or assessment of renal disease, excluding the evaluation of benign or malignant renal masses. DCE-US has been applied in clinical studies of acute kidney injury (AKI), renal transplantation, chronic kidney disease (CKD), diabetic kidney disease and to determine acute effects of pharmacological agents on renal haemodynamics. DCE-US can detect changes in renal perfusion across these clinical scenarios and can differentiate healthy controls from those with CKD. In sepsis, reduced DCE-US measures of perfusion may indicate those at increased risk of developing AKI, but this requires confirmation in larger studies as there can be wide individual variation in perfusion measures in acutely unwell patients. Recent studies in transplantation have not provided robust evidence to show that DCE-US can differentiate between different causes of graft dysfunction, although it may show more promise as a prognostic indicator of graft function 1 year after transplant. DCE-US can detect acute haemodynamic changes in response to medication that correlate with changes in renal plasma flow as measured by para-aminohippurate clearance. DCE-US shows promise and has a number of advantages that make it suitable for the assessment of patients with various forms of kidney disease. However, further research is required to evidence its reproducibility and utility before clinical use can be advocated.

Systemic haemodynamic, renal perfusion and renal oxygenation responses to changes in inspired oxygen fraction during total intravenous or volatile anaesthesia

BackgroundAnaesthesia-induced changes in renal perfusion are dependent on the choice of anaesthetic agent. However, the effects of varying inspired oxygen fraction (FiO2) on renal perfusion and oxygenation during TIVA (propofol + fentanyl) or volatile anaesthesia (VA; isoflurane) are unknown. MethodsIn 16 Merino ewes, we surgically implanted a renal artery flow probe and laser-Doppler and oxygen-sensing probes in the renal medulla and cortex. We compared the systemic and renal effects of graded alterations in FiO2 (0.21, 0.40, 0.60, and 1.0) during TIVA or VA and compared the changes with those in the non-anaesthetised state. ResultsCompared with the non-anaesthetised state, TIVA and VA decreased renal blood flow (−50% vs −75%), renal oxygen delivery (−50% vs −80%), and renal cortical (−40% vs −60%) and medullary perfusion (−50% vs −75%). At an FiO2 of 0.21, both anaesthetic regimens induced similar reductions in cortical (−58 vs −65%) and medullary (−37% vs −38%) oxygenation. At higher concentrations of FiO2, renal blood flow and renal tissue perfusion were not changed, but intrarenal oxygenation improved similarly under TIVA and VA. In particular, at an FiO2 of ≥0.40 and ≤0.60, cortical and medullary oxygen tension were similar to the non-anaesthetised state. ConclusionsIrrespective of FiO2, TIVA decreased renal and intrarenal perfusion less than VA, but at low FiO2 concentrations both led to equivalent reductions in renal cortical and medullary oxygenation. However, with FiO2 between 0.40 and 0.60 during TIVA or VA, both cortical and medullary oxygenation was maintained at normal physiological levels.

Clinical and ultrasound variables for early diagnosis of septic acute kidney injury in bitches with pyometra

The aetiology of septic acute kidney injury (AKI) is not completely elucidated. Early identification of AKI in septic patients is considered to improve survival rate since it allows rapid treatment onset. We evaluated clinical, haematological, urinary, B-mode, spectral Doppler, and contrast-enhanced ultrasound variables in 20 bitches with pyometra as sepsis models and 12 healthy controls. All animals with pyometra presented some degree of renal damage on histological examination; however, sequential organ failure assessment (SOFA) classified only 40% cases with sepsis. AKI derived from systemic infection was identified in 57% of cases with hypoperfusion and in 22% with inflammation, being an affection of multifactorial origin. Among the evaluated parameters, urinary protein/creatinine ratio >0.15, serum albumin <2.94 mg/dL, time-averaged minimum velocity <21.5 cm/s, renal length/aorta diameter ratio >5.93, pulsatility index >1.53, haematocrit <45%, time-averaged maximum velocity <45.7 cm/s, haemoglobin <16 g/dL, leukocytes >12.53 × 103/uL, and cortical contrast peak intensity <69%, in the order of accuracy, are significant indicators of septic AKI with an accuracy >80%. Thus, AKI is a very prevalent condition in septic patients, derived mainly from changes in renal perfusion and inflammation. Additionally, reviewing the SOFA score parameters is suggested to identify renal failure.

Weight-gain induced changes in renal perfusion assessed by contrast-enhanced ultrasound precede increases in urinary protein excretion suggestive of glomerular and tubular injury and normalize after weight-loss in dogs.

Early detection of obesity-related glomerulopathy in humans is challenging as it might not be detected by routine biomarkers of kidney function. This study’s aim was to use novel kidney biomarkers and contrast-enhanced ultrasound (CEUS) to evaluate the effect of obesity development and weight-loss on kidney function, perfusion, and injury in dogs. Sixteen healthy lean adult beagles were assigned randomly but age-matched to a control group (CG) (n = 8) fed to maintain a lean body weight (BW) for 83 weeks; or to a weight-change group (WCG) (n = 8) fed the same diet to induce obesity (week 0–47), to maintain stable obese weight (week 47–56) and to lose BW (week 56–83). At 8 time points, values of systolic blood pressure (sBP); serum creatinine (sCr); blood urea nitrogen (BUN); serum cystatin C (sCysC); urine protein-to-creatinine ratio (UPC); and urinary biomarkers of glomerular and tubular injury were measured. Glomerular filtration rate (GFR) and renal perfusion using CEUS were assayed (except for week 68). For CEUS, intensity- and time-related parameters representing blood volume and velocity were derived from imaging data, respectively. At 12–22% weight-gain, cortical time-to-peak, representing blood velocity, was shorter in the WCG vs. the CG. After 37% weight-gain, sCysC, UPC, glomerular and tubular biomarkers of injury, urinary immunoglobulin G and urinary neutrophil gelatinase-associated lipocalin, respectively, were higher in the WCG. sBP, sCr, BUN and GFR were not significantly different. After 23% weight-loss, all alterations were attenuated. Early weight-gain in dogs induced renal perfusion changes measured with CEUS, without hyperfiltration, preceding increased urinary protein excretion with potential glomerular and tubular injury. The combined use of routine biomarkers of kidney function, CEUS and site-specific urinary biomarkers might be valuable in assessing kidney health of individuals at risk for obesity-related glomerulopathy in a non-invasive manner.

Assessment of real‐time and quantitative changes in renal hemodynamics in healthy overweight males: Contrast‐enhanced ultrasonography vs para‐aminohippuric acid clearance

To determine the ability of renal contrast-enhanced ultrasonography (CEUS)to detect acute drug-induced changes in renal perfusion (using the glucagon-like peptide(GLP)-1 receptor agonist exenatide and nitric oxide[NO]-synthase inhibitor L-NG -monomethyl arginine[l-NMMA]), and assess its correlation with gold standard-measured effective renal plasma flow in humans. In this prespecified exploratory analysisof a placebo-controlled cross-over study, renal hemodynamics was assessed in 10 healthy overweight males (aged 20-27years; BMI 26-31kg/m2 ) over two separate testing days; during placebo (isotonic saline) and subsequent exenatide infusion (Day-A), and during l-NMMA, and subsequent exenatide plus l-NMMA infusion (Day-B). Renal cortical microvascular blood flow was estimated following microbubble infusion and CEUS destruction-refilling-sequences. Renal cortical microvascular blood flow was compared with simultaneously measured effective renal plasma flow in humans, derived from para-aminohippuric acid-clearance methodology. On Day-A, effective renal plasma flow increased by 68 [26-197]mL/min/1.73m2 during exenatide vs placebo infusion (+17%; P=.015). In parallel, exenatide increased renal cortical microvascular blood flow, from 2.42×10-4 [6.54×10-5 -4.66×10-4 ]AU to 4.65×10-4 [2.96×10-4 -7.74×10-4 ]AU (+92%; P=.027). On Day-B, effective renal plasma flow and renal cortical microvascular blood flow were reduced by l-NMMA, with no significant effect of concomitant exenatide on renal hemodynamic-indices assessed by either technique. Effective renal plasma flow correlated with renal cortical microvascular blood flow on Day-A (r=.533; P=.027); no correlation was found on Day-B. Contrast-enhanced ultrasonography can detect acute drug-induced changes human renal hemodynamics. CEUS-assessed renal cortical microvascular blood flow moderately associates with effective renal plasma flow, particularly when perfusion is in normal-to-high range. Renal CEUS cannot replace effective renal plasma flow measurements, but may be a complementary tool to characterize regional kidney perfusion.

Single-dose diclofenac in healthy volunteers can cause decrease in renal perfusion measured by functional magnetic resonance imaging.

We investigated changes of renal perfusion after topical and oral diclofenac administration in healthy volunteers using functional magnetic resonance imaging (MRI) with arterial spin labelling (ASL). Twenty-four healthy human participants (21-51years) underwent 1.5T MRI before and 1h after a single oral dose of diclofenac (50mg). Twelve of 24 participants underwent an additional MRI examination following 3-day topical diclofenac administration. For renal perfusion imaging, a flow-sensitive alternating inversion-recovery TrueFISP ASL sequence was applied. Plasma concentrations of diclofenac and serum concentrations of thromboxane were determined. After oral diclofenac application, large interindividual differences in plasma concentrations were observed (range <3-4604nm). Topical diclofenac application did not result in relevant systemic diclofenac levels (range 5-75nm). MRI showed a significant reduction of renal perfusion in individuals with diclofenac levels ≥225nm (baseline: 347±7 vs diclofenac: 323±8ml/min/100g, P<0.01); no significant differences were observed in participants with diclofenac levels <225nm. Diclofenac levels correlated negatively with thromboxane B2 levels pointing towards target engagement. Single-dose diclofenac caused a decrease in renal perfusion in participants with diclofenac levels ≥225nm. We demonstrated that even a single dose of diclofenac can impair renal perfusion, which could be detrimental in patients with underlying chronic kidney disease or acute kidney injury.

Contrast enhancement ultrasound of renal perfusion in dogs with acute kidney injury.

To evaluate the efficacy of contrast-enhanced ultrasound to assess changes in renal perfusion in dogs with acute kidney injury. The left kidney of each dog in two groups was examined using contrast-enhanced ultrasound: Group A consisted of 16 healthy dogs and Group B consisted of 12 dogs with acute kidney injury. All dogs in Group A showed the same sequence of wash-in and wash-out. In Group B the distribution of contrast media showed a similar cortical phase to healthy dogs, but a faster time to maximal medullary enhancement. Group B showed increased medullary peak intensity and medullary area under the curve compared to Group A. Both qualitative and quantitative analyses showed vascular changes especially in the medulla, with more rapid medullary vascularisation and increased medullary perfusion. These results were interpreted as medullary congestion in dogs with acute kidney injury. Contrast-enhanced ultrasound represents an easy to perform, safe, and non-invasive method to detect changes in renal perfusion in dogs with acute kidney injury.

Renal perfusion parameters measured by contrast-enhanced ultrasound in healthy dogs demonstrate a wide range of variability in the long-term.

Contrast-enhanced ultrasound may be helpful for detecting early renal microvascular damage and dysfunction in dogs. However, before this noninvasive imaging method can be tested as an early-stage screening tool in clinical patients, an improved understanding of long-term variation in healthy animals is needed. In this prospective, secondary, longitudinal, serial measurements study, variability of contrast-enhanced ultrasound renal perfusion parameters was described for eight healthy dogs, using seven time points and a period of 83weeks. Dogs were sedated with butorphanol (0.4mg/kg), and contrast-enhanced ultrasound of each kidney was performed after an intravenous bolus injection of a microbubble contrast agent (0.04mL/kg). Time-intensity curves were created from regions-of-interest drawn in the renal cortex and medulla. Intensity-related parameters representing blood volume and time-related parameters representing blood velocity were determined. A random-effects model using restricted maximum likelihood was used to estimate variance components. Within-dog coefficient of variation was defined as the ratio of the standard deviation over the mean. Time-related parameters such as time-to-peak, rise and fall time had lowest within-dog variability. Intensity-related parameters such as peak enhancement, wash-in and wash-out area under the curve, total area under the curve, and wash-in and washout rates had high within-dog variability (coefficient of variation>45%). Authors therefore recommend the use of time-related parameters for future studies of renal perfusion. Within-dog variability for bilateral kidney measurements was extremely low, therefore contrast-enhanced ultrasound may be particularly useful for detecting unilateral changes in renal perfusion. Future studies are needed to compare contrast-enhanced ultrasound findings in healthy dogs versus dogs with renal disease.

Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by Quantitative MRI during Handgrip Exercise.

Renal flow abnormalities are believed to play a central role in the pathogenesis of nephropathy and in primary and secondary hypertension, but are difficult to measure in humans. Handgrip exercise is known to reduce renal arterial flow (RAF) by means of increased renal sympathetic nerve activity. To monitor medullary and cortical oxygenation under handgrip exercise-reduced perfusion, we used contrast- and radiation-free magnetic resonance imaging (MRI) to measure regional changes in renal perfusion and blood oxygenation in ten healthy normotensive individuals during handgrip exercise. We used phase-contrast MRI to measure RAF, arterial spin labeling to measure perfusion, and both changes in transverse relaxation time (T2*) and dynamic blood oxygenation level-dependent imaging to measure blood oxygenation. Handgrip exercise induced a significant decrease in RAF. In the renal medulla, this was accompanied by an increase of oxygenation (reflected by an increase in T2*) despite a significant drop in medullary perfusion; the renal cortex showed a significant decrease in both perfusion and oxygenation. We also found a significant correlation (R2=0.8) between resting systolic BP and the decrease in RAF during handgrip exercise. Renal MRI measurements in response to handgrip exercise were consistent with a sympathetically mediated decrease in RAF. In the renal medulla, oxygenation increased despite a reduction in perfusion, which we interpreted as the result of decreased GFR and a subsequently reduced reabsorptive workload. Our results further indicate that the renal flow response's sensitivity to sympathetic activation is correlated with resting BP, even within a normotensive range.