Renal Cortical Perfusion Research Articles

Effect of intrarenal pelvic pressure on pyelo-tubular backflow and renal cortical blood perfusion during mini-percutaneous nephrolithotomy.

To investigate the effects of intrarenal pelvic pressure (IPP) on pyelo-tubular backflow and renal cortical blood perfusion during mini-percutaneous nephrolithotomy (MPCNL). Dynamic changes in pyelo-tubular backflow and renal cortical blood perfusion were studied in six patients undergoing MPCNL using dynamic contrast-enhanced ultrasonography (CEUS) and IPP monitoring. CEUS of intrarenal pelvic perfusion revealed that renal tubules began to exhibit contrast agent reflux when IPP exceeded 34 mmHg during the MPCNL procedure. There was a positive correlation between renal tubule contrast agent reflux and IPP (P < 0.05). Intravenous CEUS of renal cortical blood flow demonstrated that both intrarenal pelvic perfusion time and IPP during MPCNL significantly affected renal cortical blood perfusion. Intrarenal pelvic perfusion time and pressure were negatively correlated with contrast agent peak intensity (PI) and area under the curve (AUC) (P < 0.05). Longer intrarenal pelvic perfusion times and higher pressures resulted in decreased renal cortical blood perfusion. This study directly confirmed through dynamic CEUS and real-time IPP monitoring that an increase in IPP above the threshold of approximately 34 mmHg during MPCNL in patients leads to reflux through the renal tubules and a significant decrease in renal cortical blood perfusion. The safe upper limit for intrarenal pelvic perfusion pressure during MPCNL is approximately 34 mmHg.

Renal medullary perfusion differs from that in renal cortex in patients with sepsis associated acute kidney injury and correlates with renal function prognosis: A prospective cohort study.

Renal perfusion status remains poorly studied at the bedside during sepsis associated acute kidney injury (AKI). The aim of the study is to examine renal cortical and medullary perfusion using renal contrast enhanced ultrasound (CEUS) in septic patients. In this single-center, prospective longitudinal study, septic patients were enrolled. Renal ultrasonography was performed within 24 hours of ICU admission (D1), then repeated at D3, D5 and D7. Each measurement consisted of three destruction replenishment sequences that were recorded for delayed analysis with dedicated software (Vuebox). Renal cortex and medulla perfusion were quantified by measuring time to peak (TTP). Receiver operating characteristic (ROC) analysis was used to evaluate 28-day renal prognosis. The study included 149 septic patients, including 70 non-AKI patients and 79 AKI patients. Both renal cortical and medullary TTP was longer in the AKI group than in the non-AKI group. The difference of TTP between renal cortex and medulla in AKI group was higher than that in the non-AKI group (p = 0.000). Medullary TTP on day 3 had the best performance in predicting the prognosis of 28-day renal function (AUC 0.673, 95% confidence interval 0.528-0.818, p = 0.024), and its cut-off value was 45 s with a sensitivity 52.2% and a specificity of 82.1%. Cortical TTP on day 3 also had the performance in predicting the prognosis of 28-day renal function (AUC 0.657, 95% confidence interval 0.514-0.800, p = 0.039), and its cut-off value was 33 s with a sensitivity 78.3% and a specificity of 55.0%. Renal medullary perfusion alterations differ from those in cortex, with the medulla is worse. Simultaneous and dynamic assessment of cortical and medullary microcirculatory flow alterations necessary. TTP on day 3, especially medullary TTP, seems to be a relatively stable and useful indicator, which correlates with 28-day renal function prognosis in septic patients. Early correction of renal cortical and medullary perfusion alterations reduces the incidence of adverse renal events.

Absolute Stenosis Measures of Renal Artery Independently Influence Kidney Perfusion in Contrast-Enhanced Multidetector Computed Tomography.

Background: A renal artery lumen reduction of ≥60% indicates hemodynamically significant stenosis and is one of the main criteria for invasive revascularization. We hypothesize that direct parameters describing renal artery stenosis (RAS) could better correlate with renal blood flow and improve the criterion for revascularization. This study aimed to investigate RAS parameters independently associated with renal blood flow estimated in contrast-enhanced multidetector computed tomography (CE-MDCT). Methods: Ultrasound Doppler dynamic renal cortical perfusion (dRCP), CE-MDCT with cortical blood flow (CBF), and RAS assessment in the form of cross-sectional area reduction (CSAR), maximal diameter reduction (MaxDR), mean diameter (MeD), and minimal diameter (MinD) were investigated. Results: CBF correlated with CSAR (r = -0.422, p = 0.003), MeD (r = 0.344, p = 0.005) and MinD (r = 0.348, p= 0.005), whereas RCP correlated only with MeD (r = 0.357, p = 0.005) and MinD (r = 0.427, p< 0.001). In multivariable regression, only MeD was independently associated with CBF (R2 = 0.179; p < 0.001), and MeD < 3.5 mm substantially indicated CBF < 175 mL/100 g/min in ROC analysis. Conclusions: The directly measured mean diameter of RAS is independently associated with renal cortex blood flow and is probably a more appropriate parameter for the invasive RAS treatment criterion.

Standardized evaluation methodology for renal cortical blood perfusion in elderly patients using contrast‐enhanced ultrasound: A Chinese expert consensus (2024 edition)

AbstractAs a sensitive and non‐invasive method for assessing changes in renal cortical blood perfusion in the elderly, contrast‐enhanced ultrasound (CEUS) can indirectly reflect changes in kidney filtration and reabsorption function, thus providing feasibility for early evaluation of renal function changes. However, significant differences exist among researchers in terms of operational methods, contrast agent selection, post‐data analysis, and many other aspects, leading to substantial heterogeneity in results. This hinders horizontal comparisons and greatly limits the clinical application of contrast‐enhanced ultrasound for evaluating renal cortical blood flow perfusion. Based on the latest domestic and overseas literature and discussions with clinical experts, this consensus provides recommended guidelines for the evaluation of renal cortical blood flow perfusion using contrast‐enhanced ultrasound. It is hoped that this consensus will promote a better understanding of CEUS among medical practitioners at all levels and standardize the examination of renal cortical blood flow perfusion with CEUS.

Effects of sodium-glucose transporter-2 inhibition on systemic hemodynamics, renal function, and intra-renal oxygenation in sepsis-associated acute kidney injury

BackgroundPeople with type 2 diabetes mellitus treated with sodium-glucose transporter-2 inhibitors (SGLT2i) have lower rates of acute kidney injury (AKI). Sepsis is responsible for the majority of AKI in critically ill patients. This study investigated whether SGLT2i is renoprotective in an ovine model of Gram-negative septic AKI.MethodsSixteen healthy merino ewes were surgically instrumented to enable measurement of mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion, and oxygenation. After a 5-day recovery period, sepsis was induced via slow and continuous intravenous infusion of live Escherichia coli. Twenty-three hours later, sheep were randomized to receive an intravenous bolus of 0.2 mg/kg empagliflozin (n = 8) or a fluid-matched vehicle (n = 8).ResultsEmpagliflozin treatment did not significantly reduce renal medullary hypoperfusion or hypoxia, improve kidney function, or induce histological changes. Renal cortical oxygenation during the intervention period was 47.6 ± 5.9 mmHg in the empagliflozin group compared with 40.6 ± 8.2 mmHg in the placebo group (P = 0.16). Renal medullary oxygenation was 28.0 ± 18.5 mmHg in the empagliflozin compared with 25.7 ± 16.3 mmHg (P = 0.82). Empagliflozin treatment did not result in significant between-group differences in renal blood flow, kidney function, or renal histopathological changes.ConclusionIn a large mammalian model of septic AKI, a single dose of empagliflozin did not improve renal microcirculatory perfusion, oxygenation, kidney function, or histopathology.

Synthetic Angiotensin II ameliorates alterations of systemic hemodynamics, microcirculatory deterioration, and renal damage in septic rats

IntroductionSeptic shock is a systemic infection that causes persistent systemic hypotension, inflammation, tissue hypoperfusion and acute kidney injury (AKI). Despite norepinephrine being the currently recommended vasopressor agent, an alternative vasopressor agent that positively affects peripheral and organ microcirculatory perfusion and oxygenation is needed. This study investigated a new synthetic Angiotensin II agent suitable for improving microcirculatory parameters in a rat model of sepsis-induced systemic hemodynamic dysfunction. Methods48 mechanically ventilated, anesthetized male rats were allocated as control; lipopolysaccharide (LPS, 20 mg/kg) and LPS groups received either ringer acetate (RA), norepinephrine (NE), Angiotensin II (Ang II), or a combination of NE and Ang II. Systemic hemodynamics, renal cortical pO2 and perfusion, and muscle microcirculatory oxygen saturation were evaluated. ResultsMAP was restored in all LPS groups that received Ang II, NE, and NE + Ang II compared to the LPS group alone (p < 0.05). The deterioration of renal microcirculatory cortical oxygen, oxygen delivery, and consumption after sepsis was not restored by any of the resuscitation strategies. However, urine output was improved after Ang II resuscitation compared to the LPS and LPS + RA groups (p < 0.05). Furthermore, the muscle capillary oxygen saturation and functional capillary density (FCD) were improved by a combined infusion of NE and Ang II (p < 0.05). ConclusionsAng II can improve the MAP in rats in a way comparable to norepinephrine. Ang II increased urine output and muscle capillary oxygenation and reduced renal tissue damage. Our study supports that broad-spectrum vasopressors can benefit tissue perfusion and oxygenation in the resuscitation of septic patients.

EARLY FLUID PLUS NOREPINEPHRINE RESUSCITATION DIMINISHES KIDNEY HYPOPERFUSION AND INFLAMMATION IN SEPTIC NEWBORN PIGS.

Sepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Sepsis-induced dysregulation of kidney microcirculation in newborns is unresolved. The objective of this study was to use the translational swine model to evaluate changes in kidney function during the early phase of sepsis in newborns and the impact of fluid plus norepinephrine resuscitation. Newborn pigs (3-7-day-old) were allocated randomly to three groups: 1) sham, 2) sepsis (cecal ligation and puncture) without subsequent resuscitation, and 3) sepsis with lactated Ringer plus norepinephrine resuscitation. All animals underwent standard anesthesia and mechanical ventilation. Cardiac output and glomerular filtration rate were measured noninvasively. Mean arterial pressure, total renal blood flow, cortical perfusion, medullary perfusion, and medullary tissue oxygen tension (mtPO 2 ) were determined for 12 h. Cecal ligation and puncture decreased mean arterial pressure and cardiac output by more than 50%, with a proportional increase in renal vascular resistance and a 60-80% reduction in renal blood flow, cortical perfusion, medullary perfusion, and mtPO 2 compared to sham. Cecal ligation and puncture also decreased glomerular filtration rate by ~79% and increased AKI biomarkers. Isolated foci of tubular necrosis were observed in the septic piglets. Except for mtPO 2 , changes in all these parameters were ameliorated in resuscitated piglets. Resuscitation also attenuated sepsis-induced increases in the levels of plasma C-reactive protein, proinflammatory cytokines, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, and renal NLRP3 inflammasome. These data suggest that newborn pigs subjected to cecal ligation and puncture develop hypodynamic septic AKI. Early implementation of resuscitation lessens the degree of inflammation, AKI, and liver injury.

Effects of furosemide, acetazolamide and amiloride on renal cortical and medullary tissue oxygenation in non-anaesthetised healthy sheep.

It has been proposed that diuretics can improve renal tissue oxygenation through inhibition of tubular sodium reabsorption and reduced metabolic demand. However, the impact of clinically used diuretic drugs on the renal cortical and medullary microcirculation is unclear. Therefore, we examined the effects of three commonly used diuretics, at clinically relevant doses, on renal cortical and medullary perfusion and oxygenation in non-anaesthetised healthy sheep. Merino ewes received acetazolamide (250mg; n=9), furosemide (20mg; n=10) or amiloride (10mg; n=7) intravenously. Systemic and renal haemodynamics, renal cortical and medullary tissue perfusion and , and renal function were then monitored for up to 8h post-treatment. The peak diuretic response occurred 2h (99.4±14.8mL/h) after acetazolamide, at which stage cortical and medullary tissue perfusion and were not significantly different from their baseline levels. The peak diuretic response to furosemide occurred at 1h (196.5±12.3mL/h) post-treatment but there were no significant changes in cortical and medullary tissue oxygenation during this period. However, cortical tissue fell from 40.1±3.8mmHg at baseline to 17.2±4.4mmHg at 3h and to 20.5±5.3mmHg at 6h after furosemide administration. Amiloride did not produce a diuretic response and was not associated with significant changes in cortical or medullary tissue oxygenation. In conclusion, clinically relevant doses of diuretic agents did not improve regional renal tissue oxygenation in healthy animals during the 8h experimentation period. On the contrary, rebound renal cortical hypoxia may develop after dissipation of furosemide-induced diuresis.

Renal cortex microperfusion evaluated by laser speckle contrast imaging in an exvivo perfused kidney model-A proof-of-concept study.

Validated quantitative biomarkers for assessment of renal graft function during normothermic machine perfusion (NMP) conditions are lacking. The aim of this project was to quantify cortex microperfusion during exvivo kidney perfusion using laser speckle contrast imaging (LSCI), and to evaluate the sensitivity of LSCI when measuring different levels of renal perfusion. Furthermore, we aimed to introduce LSCI measurements during NMP in differentially damaged kidneys. Eleven porcine kidneys were nephrectomized and perfused exvivo. Cortex microperfusion was simultaneously monitored using LSCI. First, a flow experiment examined the relationship between changes in delivered renal flow and corresponding changes in LSCI-derived cortex microperfusion. Second, renal cortical perfusion was reduced stepwise by introducing a microembolization model. Finally, LSCI was applied for measuring renal cortex microperfusion in kidneys exposed to minimal damage or 2 h warm ischemia (WI). Cortex microperfusion was calculated from the LSCI-obtained data. The flow experiment resulted in relatively minor changes in cortex microperfusion compared to the pump-induced changes in total renal flow. Based on stepwise injections of microspheres, we observed different levels of cortex microperfusion that correlated with administrated microsphere dosages (r2 = 0.95-0.99). We found no difference in LSCI measured cortex microperfusion between the kidneys exposed to minimal damage (renal cortex blood flow index, rcBFI = 2090-2600) and 2 h WI (rcBFI = 2189-2540). Based on this preliminary study, we demonstrated the feasibility of LSCI in quantifying cortex microperfusion during exvivo perfusion. Furthermore, based on LSCI-measurements, cortical microperfusion was similar in kidneys exposed to minimal and 2 h WI.

Real-time laser speckle contrast imaging measurement during normothermic machine perfusion in pretransplant kidney assessment.

Normothermic machine perfusion (NMP) provides a platform for pre-transplant kidney quality assessment that is essential for the use of marginal donor kidneys. Laser speckle contrast imaging (LSCI) presents distinct advantages as a real-time and noncontact imaging technique for measuring microcirculation. In this study, we aimed to assess the value of LSCI in visualizing renal cortical perfusion and investigate the additional value of dual-side LSCI measurements compared to single aspect measurement during NMP. Porcine kidneys were obtained from a slaughterhouse and then underwent NMP. LSCI was used to measure one-sided cortical perfusion in the first 100 min of NMP. Thereafter, the inferior renal artery branch was occluded to induce partial ischemia and LSCI measurements on both ventral and dorsal sides were performed. LSCI fluxes correlated linearly with the renal blood flow (R2 = 0.90, p < 0.001). After renal artery branch occlusion, absence of renal cortical perfusion could be visualized and semiquantified by LSCI. The overall ischemic area percentage of the ventral and dorsal sides was comparable (medianinterquartile range[IQR], 38 [24-43]% vs. 29 [17-46]%, p = 0.43), but heterogenous patterns between the two aspects were observed. There was a significant difference in oxygen consumption (mean ± standard deviation [SD], 2.57 ± 0.63 vs. 1.83 ± 0.49 mLO2 /min/100 g, p < 0.001), urine output (median [IQR], 1.3 [1.1-1.7] vs. 0.8 [0.6-1.3] mL/min, p < 0.05), lactate dehydrogenase (mean ± SD, 768 ± 370 vs. 905 ± 401 U/L, p < 0.05) and AST (mean ± SD, 352 ± 285 vs. 462 ± 383 U/L, p < 0.01) before and after renal artery occlusion, while no significant difference was found in creatinine clearance, fractional excretion of sodium, total sodium reabsorption and histological damage. LSCI fluxes correlated linearly with renal blood flow during NMP. Renal cortical microcirculation and absent perfusion can be visualized and semiquantified by LSCI. It provides a relative understanding of perfusion levels, allowing for a qualitative comparison between regions in the kidney. Dual-side LSCI measurements are of added value compared to single aspect measurement and renal function markers.

Contrast-enhanced ultrasonography reveals a lower cortical perfusion and a decreased renal flow reserve in hypertensive patients.

Microvascular structural alteration and dysfunction is a hallmark of arterial hypertension. So far, the visualization and the quantification of renal microcirculation in humans has been hampered by the lack of non-nephrotoxic and non-invasive radiologic techniques. Contrast-enhanced ultrasonography (CEUS) is an appealing method to investigate renal microcirculation and has not been investigated in this setting. We aimed to compare renal microcirculation in normotensive (NT) and hypertensive (HT) participants using CEUS at rest and during a sympathetic stress test. We measured the renal perfusion index (PI, primary outcome), the renal resistive index (RRI), beat-to-beat systemic hemodynamics and plasma catecholamines before and during a 2-min cold pressor test (CPT) in NT and HT participants. Linear mixed model analysis was used to compare the effect of the CPT on the variables of interest. Seventy-three participants (32 HT) with normal kidney function were included. HT participants had a lower baseline PI compared with NT participants [median (interquartile range) 1476 (959-2155) arbitrary units (a.u.) vs 2062 (1438-3318) a.u., P<.001]. The CPT increased blood pressure, heart rate and catecholamines in all participants. The increase in PI observed in NT during the CPT was blunted in HT [+504 (117-920) a.u. vs +1159 (678-2352) a.u in NT, interaction P=.013]. Age, sex and body mass index did not modify these results. HT patients had a lower basal renal cortical perfusion. During the cold pressor test, HT participants had a smaller increase in the PI, suggesting that renal cortical flow reserve is impaired.

Systemic transit time correlates with renal cortical perfusion: a preliminary study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction We sought to measure systemic transit time (STT) on MRI dynamic sequences of images in patients based on the recirculation time. In a subset of patients, using the same images, when the abdominal aorta and at least part of one kidney was available, we used a 2-compartment filtration model to approximate renal cortical plasma perfusion (RCPF). Methods This is a retrospective study in a single site MR unit. 218 patients underwent a standard myocardial MR imaging protocol on a 1.5 Tesla MRI system including a pulse-gated, free breathing, dynamic first-pass perfusion scan of 100 phases using a saturation recovery turbo-FLASH pulse sequence (TR = 172 ms / TE = 1.1 ms / flip angle = 5°). Motion correction was applied. All patients were injected intravenously with a bolus dose of gadoteratemeglumine followed by a 20 ml saline flush. On the 218 patients studied, 20 patients were excluded due to shunts:n=5, inadequate first pass perfusion signal:n=8, fitting script did not converge on a solution:n=7. Circular ROIs were placed in the RV (Right Ventricle) and LV (Left Ventricle)cavities. The time curves for each cavity’s signals were fitted to a time-sliding 3 component-LogNormal function using an in-house python script based on the lmfit package (Levenberg-Marquardt method) to determine systemic (STT) and pulmonary transit times (PTT). In a subset of 61 patients, an attempt to measure RCPF was undertaken. An elliptic ROI was drawn in the aorta to follow arterial input. A spline polygon ROI was placed on the visible renal cortical tissue. 14 sets of images were rejected for plasma perfusion analysis for different reasons (absence of suitable abdominal aorta image, absence of suitable renal cortical image, motion artifact, …). Plasma perfusion measurements were made using a 2-compartment filtration model. Results We studied 198 sets of MRI dynamic perfusion images. Our population consists of 65,7% men aged 53,0±16,9 (mean± SD) and 34,3% women aged 55,9 ± 14,1 (mean ± SD). Fitting of the experimental data was very good in most cases (mean R² for RV:0.981, max:0.997, min: 0.907, SD:0.014) (mean R² for LV: 0.994, max:0.999, min: 0.975, SD: 0.004). An example of experimental data fitting can be seen in fig. 1. STT values were as follows: mean = 14.3 s, SD = 3.0s, max = 27.1 s, min = 8.7 s. Measures of recirculation time were highly correlated on the RV and LV side (Pearson’s R =0,975; p &amp;lt; 0,001). We found a significant correlation between STT and PTT (Pearson’s R = 0,521; p &amp;lt; 0,001). In the 47 patients where RCPF could be calculated, a significant negative correlation was found between STT and RCPF (Pearson’s R = -0,578; p &amp;lt; 0,001) (fig. 2). Conclusions Systemic transit time can be accurately measured on standard MRI perfusion scans and is negatively correlated with cortical renal plasma perfusion. Assessing systemic transit time using MRI dynamic perfusion imaging of the heart could be a usable surrogate for end-organ perfusion.

Early fluid and norepinephrine resuscitation in septic acute kidney injury diminishes pro-inflammatory cytokine levels and kidney hypoperfusion in newborn pigs

Background and Objective: Sepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Whereas sepsis-induced AKI has been studied in several animal models, alterations in renal microcirculation are unclear. The objective of this study was to use the translational swine model to evaluate the changes in renal hemodynamics during the early phase of sepsis in the first week of life. We also examined the impact of early fluid and norepinephrine (NE) resuscitation on renal hemodynamics in newborn septic AKI. Methodology: Newborn pigs (3-7 days old) were randomly allocated to three groups; 1) Sham, 2) Sepsis (cecal ligation and puncture; CLP) without subsequent resuscitation, and 3) CLP-induced sepsis with fluid and vasopressor NE resuscitation. All animals underwent standard anesthesia induction, mechanical ventilation, and intravenous fluid. Cardiac output (COP) and GFR were measured non-invasively using electrical velocimetry and a transdermal system. The pigs were instrumented to measure the mean arterial pressure (MAP), total renal blood flow (tRBF), cortical perfusion (coPf), and medullary perfusion (mePf). Also, a fiber-optic probe was placed in the medulla to measure medullary tissue oxygen tension (tPO2). Baseline values were recorded for the above indices in all groups. In resuscitated animals, fluid bolus and NE infusion were started at the 4-h to maintain MAP within 15 mmHg from baseline. The pigs were euthanized after twelve hours. Results: Compared to baseline values, MAP and COP decreased by more than two-thirds in non-resuscitated sepsis, with a proportional increase in RVR and reduction in tRBF, coPf, mePf, and tPO2 in contrast to sham. CLP also decreased GFR and increased serum creatinine, BUN, and NGAL. A few tubular coagulative necroses were observed in the septic pigs. Changes in all these parameters, except tPO2, were ameliorated in resuscitated pigs. Resuscitation also attenuated sepsis-induced increase in the levels of serum C-reactive protein, inflammatory cytokines (IL-6, IL-8, IL-12, and IL-18), liver enzymes (aspartate aminotransferase and alanine aminotransferase), and renal NLRP3 inflammasome. Conclusions: Early implementation of resuscitation to maintain MAP, COP, and kidney perfusion lessens the degree of inflammation, AKI, and liver injury in newborn pigs. The discrepancy between medullary perfusion and oxygenation indicates that optimizing perfusion and blood flow does not always correlate with improved medullary oxygen delivery in newborns, especially in cases of increased metabolic demand, as in sepsis. Sepsis is a dynamic illness with phases of hypodynamic and hyperdynamic renal perfusion; therefore, management strategies would differ based on hemodynamic status. NIH R01DK120595 and R01DK127625 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ultrasound Doppler Flow Parameters Are Independently Associated with Renal Cortex Contrast-Enhanced Multidetector Computed Tomography Perfusion and Kidney Function.

The assessment of kidney perfusion has an emerging significance in many diagnostic applications. However, whether and which of the ultrasound Doppler parameters better express renal cortical perfusion (RCP) was not shown. The study aimed to prove the usefulness of Doppler ultrasound parameters in the assessment of RCP regarding low-dose contrast-enhanced multidetector computer tomography (CE-MDCT) blood flow. Thirty non-stenotic kidneys in twenty-five hypertensive patients (age 58.9 ± 19.0) with mild-to-severe renal dysfunction were included in the study. Resistive index (RI) and end-diastolic velocity (EDV) in segmental arteries, color Doppler dynamic RCP intensity (dRCP), RI (dRI), pulsatility index (dPI), and CE-MDCT blood flow (CBF) in the renal cortex were estimated. CBF correlated significantly with age, estimated glomerular filtration rate (eGFR), RI, EDV, dRI, dPI, and dRCP. In separate multivariable backward regression analyses, RI (R2 = 0.290, p = 0.003) and dRCP (R2 = 0.320, p = 0.001) were independently associated with CBF. However, in the common ultrasound model, only dRCP was independently related to CBF (R2 = 0.317, p = 0.001). Only CBF and EDV were independently associated with eGFR (R2 = 0.510, p < 0.001). Renal cortical perfusion intensity is the best ultrasound marker expressing renal cortical perfusion. In patients with hypertension and kidney dysfunction, renal resistive index and end-diastolic velocity express renal cortical perfusion and kidney function, respectively.

Transient Receptor Vanilloid Subtype 4-Mediated Ca2+ Influx Promotes Glomerular Endothelial Inflammation in Sepsis-Associated Acute Kidney Injury

Sepsis-associated acute kidney injury (S-AKI) is a frequent complication in patients who are critically ill, which is often initiated by glomerular endothelial cell dysfunction. Although transient receptor vanilloid subtype 4 (TRPV4) ion channels are known to be permeable to Ca2+ and are widely expressed in the kidneys, the role of TRPV4 on glomerular endothelial inflammation in sepsis remains elusive. In the present study, we found that TRPV4 expression in mouse glomerular endothelial cells (MGECs) increased after lipopolysaccharide (LPS) stimulation or cecal ligation and puncture challenge, which increased intracellular Ca2+ in MGECs. Furthermore, the inhibition or knockdown of TRPV4 suppressed LPS-induced phosphorylation and translocation of inflammatory transcription factors NF-κB and IRF-3 in MGECs. Clamping intracellular Ca2+ mimicked LPS-induced responses observed in the absence of TRPV4. In vivo experiments showed that the pharmacologic blockade or knockdown of TRPV4 reduced glomerular endothelial inflammatory responses, increased survival rate, and improved renal function in cecal ligation and puncture-induced sepsis without altering renal cortical blood perfusion. Taken together, our results suggest that TRPV4 promotes glomerular endothelial inflammation in S-AKI and that its inhibition or knockdown alleviates glomerular endothelial inflammation by reducing Ca2+ overload and NF-κB/IRF-3 activation. These findings provide insights that may aid in the development of novel pharmacologic strategies for the treatment of S-AKI.

Intra-renal microcirculatory alterations on non-traumatic hemorrhagic shock induced acute kidney injury in pigs.

Acute kidney injury (AKI) is frequently seen in patients with hemorrhagic shock due to hypotension, tissue hypoxia, and inflammation despite adequate resuscitation. There is a lack of information concerning the alteration of renal microcirculation and perfusion during shock and resuscitation. The aim of this study was to investigate the possible role of renal microcirculatory alterations on development of renal dysfunction in a pig model of non-traumatic hemorrhagic shock (HS) induced AKI.Fully instrumented female pigs were divided into the two groups as Control (n = 6) and HS (n = 11). HS was achieved by withdrawing blood until mean arterial pressure (MAP) reached around 50 mmHg. After an hour cessation period, fluid resuscitation with balanced crystalloid was started for the duration of 1h. The systemic and renal hemodynamics, renal microcirculatory perfusion (contrast-enhanced ultrasound (CEUS)) and the sublingual microcirculation were measured.CEUS peak enhancement was significantly increased in HS during shock, early-, and late resuscitation indicating perfusion defects in the renal cortex (p < 0.05 vs. baseline, BL) despite a stable renal blood flow (RBF) and urine output. Following normalization of systemic hemodynamics, we observed persistent hypoxia (high lactate) and high red blood cell (RBC) velocity just after initiation of resuscitation resulting in further endothelial and renal damage as shown by increased plasma sialic acid (p < 0.05 vs. BL) and NGAL levels. We also showed that total vessel density (TVD) and functional capillary density (FCD) were depleted during resuscitation (p < 0.05).In this study, we showed that the correction of systemic hemodynamic variables may not be accompanied with the improvement of renal cortical perfusion, intra-renal blood volume and renal damage following fluid resuscitation. We suggest that the measurement of renal injury biomarkers, systemic and renal microcirculation can be used for guiding to the optimization of fluid therapies.

Correlation of renal cortical blood perfusion and BP response after renal artery stenting.

BackgroundThis study aimed to observe the correlation between renal cortical blood perfusion (CBP) parameters and BP response in patients with severe renal artery stenosis (RAS) who underwent stenting.MethodsThis was a single-center retrospective cohort study. A total of 164 patients with unilateral severe RAS after successful percutaneous transluminal renal artery stenting in Beijing Hospital from October 2017 to December 2020 were included. According to the results of BP evaluated at 12 months, all patients were divided into the BP response group (n = 98) and BP nonresponse group (n = 66). The baseline clinical and imaging characteristics and follow-up data about 24 h ABPM and CBP were recorded and analyzed. Pearson correlation analysis was used to evaluate the relationship between CBP parameters and 24 h average SBP. Univariate and multivariate logistic regression analysis was used to evaluate the risk factors for BP response.ResultsAmong 164 patients with severe RAS, there were 100 males (61.0%), aged 37–75 years, with an average of 56.8 ± 18.4 years, and average artery stenosis of 84.0 ± 12.5%. The BP nonresponse patients had a longer duration of hypertension, more current smoking subjects and diabetic patients, lower eGFR, increased number of hypertensive agents, and rate of insulin compared with the BP response group (P < 0.05). After PTRAS, patients in the BP response group were associated with significantly lower BP and improved CPB, characterized by increased levels of maximum intensity (IMAX), area under ascending curve (AUC1), area under the descending curve (AUC2), shortened rising time (RT), mean transit time (mTT), and prolonged time to peak intensity (TTP; P < 0.05). However, the BP nonresponse group was only associated with significantly reduced RT (P < 0.05) compared with baseline data. During an average follow-up of 11.5 ± 1.7 months, the BP response group was associated with significantly lower levels of SBP, DBP, 24 h average SBP, and 24 h average DBP compared with the nonresponse group (P < 0.05). Pearson correlation analysis showed that the the pre-operative CBP parameters, including IMAX (r = 0.317), RT (r = 0.249), AUC1 (r = 0.614), AUC2 (r = 0.558), and postoperative CBP parameters, including RT (r = 0.283), AUC1 (r = 0.659), and AUC2 (r = 0.674) were significantly positively correlated with the 24 h average SBP, while the postoperative TTP (r = −0.413) and mTT (r = −0.472) were negatively correlated with 24 h average SBP (P < 0.05). Multivariate Logistic regression analysis found that diabetes (OR = 1.294), NT-proBNP (OR = 1.395), number of antihypertensive agents (OR = 2.135), pre-operation IMAX (OR = 1.534), post-operation AUC2 (OR = 2.417), and baseline dDBP (OR = 2.038) were related factors for BP response (all P < 0.05).ConclusionPatients in the BP nonresponse group often have diabetes, a longer duration of hypertension, significantly reduced glomerular filtration rate, and heavier renal artery stenosis. CBP parameters are closely related to 24 h average SBP, and pre-operation IMAX and post-operation AUC2 are markers for a positive BP response.

Decreased renal cortical perfusion, independent of changes in renal blood flow and sublingual microcirculatory impairment, is associated with the severity of acute kidney injury in patients with septic shock

BackgroundReduced renal perfusion has been implicated in the development of septic AKI. However, the relative contributions of macro- and microcirculatory blood flow and the extent to which impaired perfusion is an intrinsic renal phenomenon or part of a wider systemic shock state remains unclear.MethodsSingle-centre prospective longitudinal observational study was carried out. Assessments were made at Day 0, 1, 2 and 4 after ICU admission of renal cortical perfusion in 50 patients with septic shock and ten healthy volunteers using contrast-enhanced ultrasound (CEUS). Contemporaneous measurements were made using transthoracic echocardiography of cardiac output. Renal artery blood flow was calculated using velocity time integral and vessel diameter. Assessment of the sublingual microcirculation was made using handheld video microscopy. Patients were classified based on the degree of AKI: severe = KDIGO 3 v non-severe = KDIGO 0–2.ResultsAt study enrolment, patients with severe AKI (37/50) had prolonged CEUS mean transit time (mTT) (10.2 vs. 5.5 s, p < 0.05), and reduced wash-in rate (WiR) (409 vs. 1203 au, p < 0.05) and perfusion index (PI) (485 vs. 1758 au, p < 0.05); differences persisted throughout the entire study. Conversely, there were no differences in either cardiac index, renal blood flow or renal resistive index. Sublingual microcirculatory variables were not significantly different between groups at study enrolment or at any subsequent time point. Although lactate was higher in the severe AKI group at study enrolment, these differences did not persist, and there were no differences in either ScvO2 or ScvCO2-SaCO2 between groups. Patients with severe AKI received higher doses of noradrenaline (0.34 vs. 0.21mcg/kg/min, p < 0.05). Linear regression analysis showed no correlation between mTT and cardiac index (R-0.18) or microcirculatory flow index (R-0.16).ConclusionRenal cortical hypoperfusion is a persistent feature in critically ill septic patients who develop AKI and does not appear to be caused by reductions in macrovascular renal blood flow or cardiac output. Cortical hypoperfusion appears not be associated with changes in the sublingual microcirculation, raising the possibility of a specific renal pathogenesis that may be amenable to therapeutic intervention.Trial Registration Clinical Trials.gov NCT03713307, 19 Oct 2018.

Dynamic changes of renal cortical blood perfusion before and after percutaneous transluminal renal artery stenting in patients with severe atherosclerotic renal artery stenosis.

Background:This study aims to observe the dynamic changes of renal artery (RA) disease and cortical blood perfusion (CBP) evaluated by contrast-enhanced ultrasound (CEUS) after percutaneous transluminal renal artery stenting (PTRAS) in patients with severe atherosclerotic renal artery stenosis (ARAS) and to analyze the relationship between CBP and prognosis.Methods:This was a single-center retrospective cohort study. A total of 98 patients with unilateral severe ARAS after successful PTRAS in Beijing Hospital from September 2017 to September 2020 were included. According to renal glomerular filtration rate (GFR) detected by radionuclide imaging at 12 months after PTRAS, all patients were divided into the poor prognosis group (n = 21, GFR decreased by ≥20% compared with baseline) and the control group (n = 77, GFR decreased by < 20% or improved compared with baseline). Renal artery stenosis was diagnosed by digital subtraction angiography, and renal CBP was evaluated by CEUS using TomTec Imaging Systems (Germany) before PTRAS, at 6 months and 12 months after discharge. The receiver operating characteristic (ROC) curve with area under the curve (AUC) was used to analyze the predictive value of CBP parameters, including area under ascending curve (AUC1), area under the descending curve (AUC2), rising time (RT), time to peak intensity (TTP), maximum intensity (IMAX), and mean transit time (MTT) for poor prognosis.Results:Among the 98 patients, there were 52 males (53.1%), aged 55–74 years old, with an average age of 62.1 ± 8.7 years, and an average artery stenosis of 82.3 ± 12.9%. The poor prognosis group was associated with significantly increased incidence of diabetes (76.2% vs. 41.6%), and lower levels of GFR of the stenotic kidney (21.8 mL/min vs. 25.0 mL/min) and total GFR (57.6 mL/min vs. 63.7 mL/min) (all P < 0.05), compared with the control group (P < 0.05). In addition, the rate of RA restenosis was significantly higher in the poor prognosis group than in the control group (9.5% vs. 0, χ2 = 9.462, P = 0.002). Compared with the control group, the poor prognosis group was associated with significantly decreased baseline AUC1 and AUC2, and extended duration of TTP and MTT (P < 0.05). At 6 months and 12 months of follow-up, patients in the control group were associated with markedly increased AUC1, AUC2, and IMAX, and shorter duration of RT and MTT (P < 0.05). The ROC curve showed that the predictive values of AUC1, AUC2, RT, TTP, IMAX, and MTT for poor prognosis were 0.812 (95% CI: 0.698–0.945), 0.752 (95% CI: 0.591–0.957), 0.724 (95% CI: 0.569–0.961), 0.720 (95% CI: 0.522–0.993), 0.693 (95% CI: 0.507–0.947), and 0.786 (95% CI: 0.631–0.979), respectively.Conclusions:Preoperative renal CBP in severe ARAS patients with poor prognosis is significantly reduced, and does not show significant improvement after stent treatment over the first year of follow-up. The parameter AUC1 may be a good predictor for renal dysfunction after PTRAS in severe ARAS patients.Trial Registration:ChiCTR.org.cn, ChiCTR1800016252.

Evaluation of renal microperfusion in hyperuricemic nephropathy by contrast-enhanced ultrasound imaging

ABSTRACTDiagnostic tools for the early detection of renal injury caused by hyperuricemia are still lacking. Here, we investigated whether contrast-enhanced ultrasound (CEUS) could be used as a diagnostic tool for hyperuricemic nephropathy (HN). In the HN rat model, CEUS detected a significant decline in renal cortical perfusion compared with that in control rats. Peak intensity (PI) values correlated significantly with serum KIM-1 levels and fibrosis scores in HN rats. An early decline in PI values was also observed in chronic kidney disease (CKD) stage 1 patients with HN compared with the controls (61.1±4.52 dB versus 65.80±7.10 dB) and correlated with renal function in the patients with HN. In contrast, an increase in time to reach PI values was detected in HN patients with stage 1 CKD (15.14±1.75 s versus 14.52±4.75 s) and was more pronounced in CKD stage 4 patients (67.32±3.29 s). CEUS was able to detect abnormal renal perfusion in early CKD with HN, which correlated with renal function decline, suggesting that CEUS could be used as a noninvasive tool for assessing renal function in patients with HN.