Renal Hemodynamics Research Articles

Effect of controlled hypotensive hemorrhage on plasma sodium levels in anesthetized pigs: An exploratory study.

Perioperative hyponatremia, due to non-osmotic release of the antidiuretic hormone arginine vasopressin, is a serious electrolyte disorder observed in connection with many types of surgery. Since blood loss during surgery contributes to the pathogenesis of hyponatremia, we explored the effect of bleeding on plasma sodium using a controlled hypotensive hemorrhage pig model. After 30-min baseline period, hemorrhage was induced by aspiration of blood during 30 min at mean arterial pressure <50 mmHg. Thereafter, the animals were resuscitated with retransfused blood and a near-isotonic balanced crystalloid solution and monitored for 180 min. Electrolyte and water balances, cardiovascular response, renal hemodynamics, and markers of volume regulation and osmoregulation were investigated. All pigs (n = 10) developed hyponatremia. All animals retained hypotonic fluid, and none could excrete net-free water. Urinary excretion of aquaporin 2, a surrogate marker of collecting duct responsiveness to antidiuretic hormone, was significantly reduced at the end of the study, whereas lysine vasopressin, i.e., the pig antidiuretic hormone remained high. In this animal model, hyponatremia developed due to net positive fluid balance and generation of electrolyte-free water by the kidneys. A decreased urinary aquaporin 2 excretion may indicate an escape from antidiuresis.

Chemogenetic Activation of Pericytes Alters Systemic and Renal Hemodynamics

Chemogenetic Activation of Pericytes Alters Systemic and Renal Hemodynamics

An adolescent female with intentional ingestion of a large amount of metformin requiring extracorporeal membrane oxygenation and continuous renal replacement therapy

Acute overdose of metformin can show potentially fatal lactic acidosis. Management should be directed towards close monitoring of renal function and hemodynamics. Patients may require dialysis or extracorporeal membrane oxygenation in cases of hemodynamic instability. This case presents an adolescent with massive metformin ingestion estimated at 100 g leading to metformin-associated lactic acidosis and subsequent respiratory failure, cardiovascular collapse, and acute kidney injury. The complications were successfully managed with venoarterial extracorporeal membrane oxygenation, continuous renal replacement therapy, and mechanical ventilation.

Comparative evaluation of fetal renal artery hemodynamics in normohydramnios, idiopathic oligohydramnios and polyhydramnios in third trimester pregnancy

AbstractObjectiveTo compare the renal artery (RA) flow indices (RI and PI) among normohydramnios, idiopathic oligohydramnios, and polyhydramnios and determine applicability of fetal RA Doppler indices in predicting the pregnancy outcome.MethodsTotal 106 3rd trimester pregnant patients were divided into cases and controls based on amniotic fluid index. Routine antenatal and color Doppler (including kidneys) ultrasound was performed for all patients in this study. The postnatal follow‐up was done, and the pregnancies having poor outcomes in terms of NICU admissions were assessed.ResultsStatistically significant differences were noted when comparing RI and PI values of normohydramnios (0.91 ± 0.04 and 2.38 ± 0.21, respectively) with oligohydramnios (1.02 ± 0.07 and 2.99 ± 0.38, respectively) and polyhydramnios (0.90 ± 0.12 and 2.7 ± 0.84, respectively) independently (p value &lt; 0.05). Our study demonstrated an increase in NICU admissions in the fetus having raised values of RI and PI.ConclusionFetal RA RI and PI can be used as an antenatal predictor for the pregnancy outcome associated with idiopathic oligohydramnios; however, fetal RA PI was found to be a better predictor for the pregnancy outcome than fetal RA RI value in our study.

Maternal dexamethasone exposure does not affect glucose tolerance but alters renal haemodynamics in F1 rats in a sex-dependent manner.

Prenatal programming with dexamethasone increases the risk of the development of hyperglycaemia and insulin resistance, leading to diabetes in adulthood. Dexamethasone also causes a decline in renal glomerular filtration in the adult offspring. Sodium-glucose cotransporter-2 (SGLT2) plays a significant role in regulating blood glucose and renal haemodynamics in diabetic patients. However, the role of SGLT2 in dexamethasone-induced programming and the putative sex-dependent effects on the changes named earlier is unknown. Therefore, this study aimed to investigate the impact of maternal dexamethasone treatment on glucose tolerance, insulin sensitivity, renal perfusion and renal function in adult male and female offspring and the possible contribution of SGLT2 to these changes. Pregnant Sprague Dawley rats (F0 ) were treated with either vehicle or dexamethasone (0.2 mg/kg ip) from gestation Day 15 to 20. F1 males and F1 females were randomly selected from each mother at 4 months of age. There was no change in serum Na+ , Na+ excretion rate, glucose tolerance or insulin sensitivity in F1 male or female rats. However, dexamethasone caused significant glomerular hypertrophy and decreases in CSinistrin and CPAH indicating decreased glomerular filtration rate and renal plasma flow, respectively, in dexamethasone-treated F1 male but not female rats. Dexamethasone did not affect SGLT2 mRNA or protein expression in F1 males or females. We conclude that dexamethasone-mediated prenatal programming of glomerular volume, renal function and haemodynamics is sex-dependent, occurring only in adult male offspring.

Efficacy of Dynamics-based Features for Machine Learning Classification of Renal Hemodynamics.

Different machine learning approaches for analyzing renal hemodynamics using time series of arterial blood pressure and renal blood flow rate measurements in conscious rats are developed and compared. Particular emphasis is placed on features used for machine learning. The test scenario involves binary classification of Sprague-Dawley rats obtained from two different suppliers, with the suppliers' rat colonies having drifted slightly apart in hemodynamic characteristics. Models used for the classification include deep neural network (DNN), random forest, support vector machine, multilayer perceptron. While the DNN uses raw pressure/flow measurements as features, the latter three use a feature vector of parameters of a nonlinear dynamic system fitted to the pressure/flow data, thereby restricting the classification basis to the hemodynamics. Although the performance in these cases is slightly reduced in comparison to that of the DNN, they still show promise for machine learning (ML) application. The pioneering contribution of this work is the establishment that even with features limited to hemodynamics-based information, the ML models can successfully achieve classification with reasonably high accuracy.

Abstract P137: Lack Of Atrial Natriuretic Peptide Aggravates Glomerular Disease In Type 1 Diabetic Nephropathy

Introduction: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and DKD patients have a significantly higher risk of developing cardiovascular disease. Some studies have suggested the role of the Atrial Natriuretic Peptide (ANP) in DKD development. ANP is a cardiac hormone that regulates renal salt/water homeostasis and plays a major role in renal hemodynamics. We hypothesized here that ANP plays a critical role in T1DKD, playing a potential protective role in podocytes of the glomeruli. Methods: We used the ANP knock-out (SS NPPA-/- ) rat on the Dahl Salt-Sensitive (Dahl SS) background injected with streptozotocin (STZ; 75mg/kg) as a model of T1DKD. At 9-10 weeks of age, male SS NPPA-/- and Dahl SS wild-type (SS WT ) rats were i.p. injected with either STZ or vehicle. Baseline, midpoint, and endpoint blood glucose, urine, and body weights were collected. Glomerular filtration rate (GFR) was assessed before animals were. Glomerular injury was scored blindly on a scale from 0-4 (0 = healthy glomerulus, 4 = severely sclerosed) in Masson Trichrome stained kidneys. One-way ANOVA through Origin 2019b was used for statistical analysis. Results: STZ- SS WT and STZ-SS NPPA-/- groups exhibited similar body weight (237.8 ± 18.9 vs. 234.5 ± 10.03 g, respectively), two-kidney weight to body weight ratio (32.1 ± 1.6 vs. 29.4 ± 1.6 mg/g, respectively), and endpoint blood glucose levels (&gt;650 mg/dL). Interestingly, we observed a significantly higher heart to body weight ratio for the STZ-SS NPPA-/- vs STZ- SS WT rats (7.0 ± 0.33 vs. 5.1 ± 0.07 mg/g, respectively, p&lt;0.05). STZ- SS WT and STZ-SS NPPA-/- had similar diuresis (54.4 ± 2.8 vs. 52.5 ± 4.01 mL/24hr/100gTBW, respectively). Importantly, histological analysis displayed a more profound glomerular injury in the STZ-SS NPPA-/- when they were compared to STZ- SS WT (3.4 ± 0.02 vs. 3.2 ± 0.03 au, respectively, p&lt;0.05). Conclusion: Thus far the data suggest that lack of ANP has a detrimental impact on DKD-related renal tissue damage, specifically, glomerular disease progression. Future studies will provide mechanistic insight into the role of ANP in oxidative stress and assess the role of ANP in nitric oxide production and calcium transients in the podocyte.

Abstract P212: NMDA Receptor Glutn2c Deficient Mouse Associates With Hypertension

Introduction: N-methyl-D-Aspartate (NMDA) receptors are glutamate receptors located in the CNS and peripheral tissues. We previously showed that kidney NMDA receptors in the connecting/collecting ducts (CNT/CCD) participate in renal autoregulation and kidney vasodilation. We also showed that the use of non-specific NMDA inhibitors increases blood pressure. This work aims to identify which NMDA receptor subtypes are associated with hypertension. Methods: We simultaneously evaluated the expression of GluN2C and 2D in the CNT/CCD by using in-situ hybridization (RNA scope) with the presence of CNT/CCD marker AQP-2 using immunofluorescence. Blood pressure was evaluated in C57B mice and global genetic ablated mice on C57B background: GluN2C-KO or GluN2D-KO. Blood pressure was measured using the tail-cuff method three times a week for two weeks after three sesión training. We used both male and female mice. Animals were fed on regular and high salt diets (4%). Results: RNA expression of NMDA subunits 2C and 2D were found to be present in AQP2-positive regions from mouse kidneys, compatible with CNT/CCD regions. The average systolic blood pressure (SBP) for C57B control mice was 105.6±10.5 mmHg; on GluN2C-KO mice, SBP was 114.6±7.3 mmHg, significantly elevated compared to the matched C57B control mice (p&lt;0.01), and GluN2D mice’s SBP was 111.6±10.4 mmHg with no significant differences from the matched control (111.1±4.6 mmHg; p=0.93). No difference was observed between male and female mice in both genetically ablated mice. After a challenge with a high salt diet, blood pressure did not change in all three groups. Conclusion: NMDA receptors subunits GluN2C and GluN2D are expressed in the CNT/CCD region. The genetic absence of GlutN2C is associated with high blood pressure; however, the lack of GLUN2D did not change SBP. No salt sensitivity was observed in any of the genetically ablated mice. Future work will explore the role of renal hemodynamics in these blood pressure phenotypes.

Renal hemodynamics in patients with resistant hypertension and type 2 diabetes mellitus.

Aim To study renal hemodynamics in patients with resistant arterial hypertension (RAH) in combination with type 2 diabetes mellitus (DM2) and to identify factors involved in the increase in intrarenal vascular resistance.Material and methods This study included 59 patients (25 men) with RAH in combination with DM2. Mean age of patients was 60.3±7.9 years; 24-h blood pressure (24-BP) (systolic, diastolic, SBP/DBP) was 158.0±16.3 / 82.5±12.7 mm Hg during the treatment with 4.3 [4.0;5.0] antihypertensive drugs; glycated hemoglobin (HbA1c) was 7.5±1.5 %; estimated glomerular filtration rate (eGFR) was 73.1±21.8 ml/min / 1.73 m2 (CKD-EPI equation). Measurement of office BP, 24-h BP monitoring, renal artery (RA) Doppler, routine lab tests including determination of GFR (CKD-EPI), 24-h urine albumin excretion, and ELISA measurement of blood lipocalin-2, cystatin C, high-sensitive C-reactive protein (hsCRP), and asymmetric dimethylarginine (ADMA) were performed for all patients.Results Incidence of increased RA resistive index (RI) was 39% despite the high rate of vasodilator treatment (93% for renin-angiotensin-aldosterone system inhibitors, 78% for calcium antagonists). According to a correlation and regression analysis, RA RI values were correlated with the kidney function (r=-0.46, p&lt;0.001 for eGFR, r=0.56; p=0.006 for lipocalin-2), age (r=0.54, p&lt;0.001), increases in concentrations of hsCRP (r=0.35, p&lt;0.001) and ADMA (r=0.39, p=0.028), the increase in vascular stiffness (r=0.59, p&lt;0.001 for pulse BP (PBP) as well as DM2 duration, and HbA1c (r=0.33, p&lt;0.001 for both). The independent association of RA RI with the age, PBP, and duration of DM2 was confirmed by the results of multivariate regression analysis. According to the ROC analysis, the threshold level of RA RI corresponding to a decrease in GFR &lt;60 ml / min / 1.73 m2 was ≥0.693 conv. units.Conclusion In more than one third of patients with RAH in combination with DM2, increased renal vascular resistance was documented, which was closely associated with impaired kidney function, age, DM2 duration and severity, and markers of low-grade inflammation, endothelial dysfunction, and vascular stiffness. The value of RA RI ≥0.693 conv. units was a threshold for the development of chronic kidney disease (CKD).

Drug–drug interaction signals between loop diuretics and teicoplanin during acute kidney injury evaluated using Japanese spontaneous adverse drug event reports

Teicoplanin can cause acute kidney injury, but little is known about the risk of acute kidney injury when teicoplanin is co-administered with loop diuretics (a powerful diuresis), which can alter renal hemodynamics and glomerular filtration rate. We performed a signal detection analysis using a Japanese adverse event database to determine the additive impact of loop diuretics on acute kidney injury associated with teicoplanin. The dataset originated between April 2004 and August 2022. Disproportionality analysis was performed to detect the signals for acute kidney injury (the Standardized MedDRA Query) when co-administered teicoplanin or vancomycin (a positive control) with individual diuretics, including loop diuretics. Multivariate logistic regression analysis was tested to estimate the adjusted reporting odds ratio (aROR) and 95% confidence interval (95% CI). There were 147 and 515 events of acute kidney injury associated with teicoplanin and vancomycin, respectively. A significant positive signal for acute kidney injury when teicoplanin was co-administered with loop diuretics was present (aROR 4.83, 95% CI 3.52–6.61, p < 0.0001). Contrastingly, no significant signals were observed when vancomycin was co-administered with any diuretics. These findings suggest that co-administered loop diuretics may have an unfavorable effect on acute kidney injury while undertaking teicoplanin but not vancomycin.

Geniposide ameliorates acute kidney injury via enhancing the phagocytic ability of macrophages towards neutrophil extracellular traps

Acute kidney injury (AKI) is a clinically serious disorder associated with high mortality rates and an increased risk of progression to end-stage renal disease. As an essential supportive treatment for patients with respiratory failure, mechanical ventilation not only save many critically ill patients, but also affect glomerular filtration function by changing renal hemodynamics, neurohumoral and positive end-expiratory pressure, eventually leading to AKI. AMP-activated protein kinase (AMPK), a crucial energy homeostasis regulator, could enhance macrophage phagocytic ability and inhibit inflammation, but whether it can engulf neutrophil extracellular traps (NETs) and alleviate mechanical ventilation-associated AKI is still unclear. In this study, we found that geniposide significantly ameliorated histopathological damage, reduced serum Cre and BUN levels. Besides, geniposide can also induce AMPK activation and enhance macrophage phagocytic ability toward NETs. Moreover, geniposide can markedly reduce the levels of high mobility group box 1 (HMGB1), and these effects were dependent on AMPK-PI3K/Akt signaling. Altogether, these results indicated that geniposide promoted macrophage efferocytosis by inducing AMPK-PI3K/Akt signaling activation, clearing NETs and ameliorating AKI.

The role of Mas receptor on renal hemodynamic responses to angiotensin II administration in chronic renal sympathectomized male and female rats.

Renal hemodynamics is influenced by renal sympathetic nerves and the renin-angiotensin system. On the other hand, renal sympathetic denervation impacts kidney weight by affecting renal hemodynamics. The current study evaluated the role of the Mas receptor on renal hemodynamic responses under basal conditions and in response to angiotensin II (Ang II) in chronic renal sympathectomy in female and male rats. Forty-eight nephrectomized female and male rats were anesthetized and cannulated. Afterward, the effect of chronic renal sympathectomy was investigated on hemodynamic parameters such as renal vascular resistance (RVR), mean arterial pressure (MAP), and renal blood flow (RBF). In addition, the effect of chronic sympathectomy on kidney weight was examined. Chronic renal sympathectomy increased RVR and subsequently decreased RBF in both sexes. Renal perfusion pressure also increased after sympathectomy in male and female rats, while MAP did not change, significantly. In response to the Ang II injection, renal sympathectomy caused a greater decrease in RBF in all experimental groups, while it did not affect the MAP response. In addition, chronic sympathectomy increased left kidney weight in right nephrectomized rats. Chronic renal sympathectomy changed systemic/renal hemodynamics in baseline conditions and only renal hemodynamics in response to Ang II administration. Moreover, chronic sympathectomy increased compensatory hypertrophy in nephrectomized rats. These changes are unaffected by gender difference and Mas receptor blocker.

Role of Alström syndrome 1 in the regulation of glomerular hemodynamics.

Inactivating mutations in the ALMS1 gene in humans cause Alström syndrome, characterized by the early onset of obesity, insulin resistance, and renal dysfunction. However, the role of ALMS1 in renal function and hemodynamics is unclear. We previously found that ALMS1 is expressed in thick ascending limbs, where it binds and decreases Na+-K+-2Cl- cotransporter activity. We hypothesized that ALMS1 is expressed in macula densa cells and that its deletion enhances tubuloglomerular feedback (TGF) and reduces glomerular filtration rate (GFR) in rats. To test this, homozygous ALMS1 knockout (KO) and littermate wild-type Dahl salt-sensitive rats were studied. TGF sensitivity was higher in ALMS1 KO rats as measured by in vivo renal micropuncture. Using confocal microscopy, we confirmed immunolabeling of ALMS1 in macula densa cells (nitric oxide synthase 1 positive), supporting a role for ALMS1 in TGF regulation. Baseline glomerular capillary pressure was higher in ALMS1 KO rats, as was mean arterial pressure. Renal interstitial hydrostatic pressure was lower in ALMS1 KO rats, which is linked to increased Na+ reabsorption and hypertension. GFR was reduced in ALMS1 KO rats. Seven-week-old ALMS1 KO rats were not proteinuric, but proteinuria was present in 18- to 22-wk-old ALMS1 KO rats. The glomerulosclerosis index was higher in 18-wk-old ALMS1 KO rats. In conclusion, ALMS1 is involved in the control of glomerular hemodynamics in part by enhancing TGF sensitivity, and this may contribute to decreased GFR. Increased TGF sensitivity, enhanced glomerular capillary pressure, and hypertension may lead to glomerular damage in ALMS1 KO rats. These are the first data supporting the role of ALMS1 in TGF and glomerular hemodynamics.NEW & NOTEWORTHY ALMS1 is a novel protein involved in regulating tubuloglomerular feedback (TGF) sensitivity, glomerular capillary pressure, and blood pressure, and its dysfunction may reduce renal function and cause glomerular damage.

Role of Magnesium in Diabetic Nephropathy for Better Outcomes.

Diabetic nephropathy (DN) is a major cause of end-stage renal disease worldwide, resulting from uncontrolled diabetes. Oxidative stress plays a critical role in the pathophysiology of DN, leading to cellular damage and disease progression. Magnesium, an essential mineral, has emerged as a potential therapeutic agent due to its antioxidative, anti-inflammatory, and antifibrotic properties. An extensive literature search was conducted on Medline using the keywords "Diabetic nephropathy," "Magnesium," and "Chronic Kidney Disease," and the results published after 2000 were exclusively studied to build this review. This review aims to summarize the role of magnesium in DN and explore its therapeutic potential. Magnesium acts as a cofactor for antioxidant enzymes, directly scavenges reactive oxygen species, and enhances the expression of antioxidant proteins. Furthermore, magnesium exhibits anti-inflammatory effects by suppressing pro-inflammatory cytokine production and inhibiting inflammatory signaling pathways. Magnesium supplementation has been shown to reduce oxidative stress markers and improve antioxidant enzyme activities in clinical studies. Additionally, magnesium has been found to mitigate renal fibrosis, maintain tubular integrity and function, improve endothelial function, and modulate renal hemodynamics. Although limited clinical trials suggest the renoprotective effects of magnesium in DN, further research is needed to determine the optimal dosage, duration, and long-term effects of magnesium supplementation. Despite existing drawbacks and gaps in the literature, magnesium holds promise as adjunctive therapy for DN by targeting oxidative stress and preserving renal function.

Rationale and study design of a randomized controlled trial to investigate the renoprotective effect of canagliflozin assessed by test of renal hemodynamics in diabetic kidney disease (the FAGOTTO study)

BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) are considered to have the potential to maintain renal function by correcting glomerular hypertension in patients with diabetic kidney disease (DKD). The aim of this study is to demonstrate the renoprotective effect of SGLT2i by measuring renal hemodynamics, including glomerular filtration fraction (FF), in type 2 diabetic patients with moderate renal dysfunction.MethodsRenoprotective effect of canagliflozin derived from test of renal hemodynamics in diabetic kidney disease (FAGOTTO) study is a 12-week multicenter, open-label, randomized (1:1), parallel-group trial of type 2 diabetic patients with diabetic kidney disease (30 ≤ estimated glomerular filtration rate [eGFR] ≤ 60 mL/min/1.73 m2). A total of 110 patients are to be randomly allocated to receive once-daily canagliflozin 100 mg or control (standard therapy). FF will be calculated by dividing the measured GFR (mGFR) by the effective renal plasma flow (eRPF). mGFR and eRPF will be measured by the clearance of inulin and para-aminohippuric acid (PAH), respectively. The primary endpoint of this trial is the percentage change in FF after 4 weeks of treatment in the canagliflozin and control groups.DiscussionThe FAGOTTO study will elucidate the mechanism of the renoprotective action of SGLT2i. The background, rationale, and study design of this trial are presented. To date, > 80 patients have been enrolled in this trial. The study will end in 2025.Trial registrationjRCT (Japan Registry Of Clinical Trials) jRCTs041200069. Date of registration: November 27, 2020.

Reno- and cardioprotective molecular mechanisms of SGLT2 inhibitors beyond glycemic control - from bedside to bench.

Large placebo-controlled clinical trials have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) delay the deterioration of renal function and reduce cardiovascular events in a glucose-independent manner, thereby ultimately reducing mortality in patients with chronic kidney disease (CKD) and/or heart failure. These exiting clinical data stimulated preclinical studies aiming to understand the observed clinical effects. In animal models, it was shown that the beneficial effect of SGLT2i on the tubuloglomerular feedback (TGF) improves glomerular pressure and reduces tubular workload by improving renal haemodynamics, which appears to be dependent on salt intake. High salt intake might blunt the SGLT2i effects on the TGF. Beyond the salt-dependent effects of SGLT2i on renal haemodynamics, the beneficial effects of SGLT2i on CKD progression are at least partly mediated by targeting TGF-β1 and or STAT3 and or AMPK signaling pathways affecting macrophage differentiation and polarization as well as inhibiting the activation of inflammatory factors within macrophages. As macrophages are also important cells mediating atherosclerosis and myocardial remodeling after injury, the inhibitory effects of SGLT2i on macrophage differentiation and inflammatory responses may also play a role in stabilizing atherosclerotic plaques and ameliorating myocardial inflammation and fibrosis. Recent studies suggest that SGLT2i may also act directly on the Na+/H+ exchanger and Late-INa in cardiomyocytes thus reducing Na+ and Ca2+ overload-mediated myocardial damage, but studies in this area are limited. In addition, the renal-cardioprotective mechanisms of SGLT2i include systemic effects on the sympathetic nervous system, blood volume, salt excretion and energy metabolic patterns.

Artificial Intelligence Assisted Multi-modal Photoacoustic-Ultrasound Imaging for Studying Renal Tissue Function and Hemodynamics.

Combined functional-anatomic imaging modalities, which integrate the benefits of visualizing gross anatomy along with the functional or metabolic information of tissue has revolutionized the world of medical imaging. However, such existing imaging modalities are very costly. An alternative option could be a hybrid modality combining contrast-enhanced ultrasound, doppler and photoacoustic imaging. In the current study, we propose an artificial intelligence assisted multi-modal imaging platform where we have used U-net model for segmenting the anatomical features from the ultrasound images obtained from an animal model study. The neural network has performed accurately for three different cases, each with a high dice score. The model was co-validated with doppler images. Further, blood perfusion and tissue oxygenation information from the predicted anatomical structures were also studied. The present findings confirm the feasibility of using this multimodal imaging modality facilitated by artificial intelligence for better understanding of the hemodynamics of the kidney.Clinical Relevance-A multi-modal imaging technique has been proposed which would provide anatomical and functional information to the clinicians for early detection and tracking of the disease prognosis. Unlike existing imaging modalities like PET-CT (Positron Emission Tomography- Computed Tomography), the proposed modality is much more costeffective and radiation free (non-ionizing nature).

Elevated urinary angiotensinogen excretion links central and renal hemodynamic alterations

Inappropriate activation of intrarenal renin–angiotensin system (RAS) may contribute to the pathogenesis of cardio-renal syndrome (CRS). We aimed to examine the cross-sectional associations of urinary angiotensinogen (AGT) excretion, a biomarker of intrarenal RAS activity, with central (aortic) and renal hemodynamic parameters in middle-aged and older adults, including patients with chronic kidney disease. Aortic and renal hemodynamic parameters were measured using applanation tonometry and duplex ultrasonography in 282 participants. Urinary AGT, liver-type fatty acid-binding protein (L-FABP), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured for each participant. Multiple linear regression analyses demonstrated that urinary AGT levels were associated with aortic blood pressures, pulsatile measures of renal blood flow, plasma NT-proBNP and urinary L-FABP levels after adjusting for potential covariates, including age, sex, body mass index, estimated glomerular filtration rate (GFR), and medication use. Additionally, when classified based on GFR stages and urinary AGT levels, plasma NT-proBNP and urinary L-FABP levels increased in participants with lower GFR and higher AGT groups. Our findings suggest that urinary AGT excretion is a shared determinant of central (aortic) and renal hemodynamics in middle-aged and older adults, providing clinical evidence for the potential role of intrarenal RAS activity in the development of CRS.

The differences in renal hemodynamic response following high-intensity exercise between younger and older males.

Renal blood flow (RBF) decreases with exercise, but this change is only temporary, and habitual exercise may be an effective method to improve renal function. The kidney shows structural and functional changes with aging, but it is unclear how aging affects the hemodynamic response of the kidneys to exercise. Therefore, we evaluated the differences in the hemodynamic response of the kidneys to high-intensity exercise between younger and older men. Sixteen men (8 young and 8 older) underwent an incremental exercise test using a cycle ergometer with a 1-min warm up followed by exercise at 10-20 W/min until the discontinuation criteria were met. Renal hemodynamics were assessed before exercise, immediately after exercise, and at 60-min after exercise using ultrasound echo. High-intensity exercise significantly reduced RBF in both groups (younger: ∆ - 53 ± 16%, p = 0.0005; older: ∆ - 53 ± 19%, p = 0.0004). In the younger group, RBF returned to the pre-exercise level 60-min after exercise (∆ - 0.4 ± 5.7%, p > 0.9999). In contrast, RBF 60-min after exercise was significantly lower than that before exercise in the older group (∆ - 24 ± 19%, p = 0.0006). The older group had significantly lower RBF than younger adults 60-min after exercise (423 ± 32 vs. 301 ± 98mL/min, p = 0.0283). Our findings demonstrate that RBF following high-intensity exercise recovered 60-min after exercise in younger group, whereas RBF recovery was delayed in the older group.

Association between intrarenal venous flow from Doppler ultrasonography and acute kidney injury in patients with sepsis in critical care: a prospective, exploratory observational study

BackgroundIntrarenal venous flow (IRVF) patterns assessed using Doppler renal ultrasonography are real-time bedside visualizations of renal vein hemodynamics. Although this technique has the potential to detect renal congestion during sepsis resuscitation, there have been few studies on this method. We aimed to examine the relationship between IRVF patterns, clinical parameters, and outcomes in critically ill adult patients with sepsis. We hypothesized that discontinuous IRVF was associated with elevated central venous pressure (CVP) and subsequent acute kidney injury (AKI) or death.MethodsWe conducted a prospective observational study in two tertiary-care hospitals, enrolling adult patients with sepsis who stayed in the intensive care unit for at least 24 h, had central venous catheters placed, and received invasive mechanical ventilation. Renal ultrasonography was performed at a single time point at the bedside after sepsis resuscitation, and IRVF patterns (discontinuous vs. continuous) were confirmed by a blinded assessor. The primary outcome was CVP obtained at the time of renal ultrasonography. We also repeatedly assessed a composite of Kidney Disease Improving Global Outcomes of Stage 3 AKI or death over the course of a week as a secondary outcome. The association of IRVF patterns with CVP was examined using Student's t-test (primary analysis) and that with composite outcomes was assessed using a generalized estimating equation analysis, to account for intra-individual correlations. A sample size of 32 was set in order to detect a 5-mmHg difference in CVP between IRVF patterns.ResultsOf the 38 patients who met the eligibility criteria, 22 (57.9%) showed discontinuous IRVF patterns that suggested blunted renal venous flow. IRVF patterns were not associated with CVP (discontinuous flow group: mean 9.24 cm H2O [standard deviation: 3.19], continuous flow group: 10.65 cm H2O [standard deviation: 2.53], p = 0.154). By contrast, the composite outcome incidence was significantly higher in the discontinuous IRVF pattern group (odds ratio: 9.67; 95% confidence interval: 2.13–44.03, p = 0.003).ConclusionsIRVF patterns were not associated with CVP but were associated with subsequent AKI in critically ill adult patients with sepsis. IRVF may be useful for capturing renal congestion at the bedside that is related to clinical patient outcomes.Graphical abstract