Correlation of Internal Jugular Vein Collapsibility With Central Venous Pressure in Patients With Liver Cirrhosis.

We aimed to compare internal jugular vein and inferior vena cava ultrasonography as predictors of central venous pressure in cirrhotic patients. We performed ultrasound assessments of the internal jugular vein (IJV) and the inferior vena cava and then invasively measured central venous pressure (CVP). We then compared their correlation with CVP and performed area under the receiver operating characteristic curves to determine which had best sensitivity and specificity. IJV cross-sectional area collapsibility index at 30° correlated better with CVP ( r = -0.56, P < 0.001), and an IJV AP-CI at 30° ≤ 24.8% was better at predicting a CVP ≥8 mm Hg, with 100% sensitivity and 97.1% specificity. Thus, IJV point-of-care ultrasound might be superior than inferior vena cava point-of-care ultrasound as a predictor of CVP in cirrhotic patients.

The burden of chronic kidney disease in Mexico: data analysis based on the Global Burden of Disease 2021 study.

BACKGROUND: Chronic kidney disease (CKD) represents a substantial global burden of disease due to a lack of universal tests and misinterpretation of biomarkers. OBJECTIVE: To analyze CKD epidemiology in Mexico and guide public policies. MATERIAL AND METHODS: Data from the Global Burden of Disease (GBD) 2021 study were used to describe CKD prevalence and mortality in Mexico for the 1990-2021 period, stratifying by gender and age groups. RESULTS: The prevalence of CKD in Mexico in 2021 was 9,184.9 per 100,000 population. Diabetes was the most common cause of CKD, and CKD-related mortality was high, with an increase in 2019 and 2021, possibly as a consequence of the COVID-19 pandemic. CONCLUSIONS: CKD in Mexico entails a high burden of mortality and years of life lost, but it barely contributes to disability. It is essential to improve CKD early detection, access to treatments and coding of the causes of the disease. Moreover, investigating the causes of CKD of unknown etiology, including genetic factors, is crucial in order for specific treatments to be developed in the future.

ANTECEDENTES: La enfermedad renal crónica (ERC) representa una elevada carga global de enfermedad debido a la falta de pruebas universales y a la interpretación errónea de biomarcadores. OBJETIVO: Analizar la epidemiología de la ERC en México y orientar las políticas públicas. MATERIAL Y MÉTODOS: Se utilizaron los datos del estudio Global Burden of Disease (GBD) 2021 para describir la prevalencia y mortalidad de la ERC en México durante el periodo de 1990 a 2021, estratificando por sexo y grupos de edad. RESULTADOS: La prevalencia de la ERC en México en 2021 fue de 9184.9 por 100 000 habitantes. La diabetes constituyó la causa más común de ERC y la mortalidad por ERC fue elevada, se incrementó en 2019 y 2021, posiblemente debido a la pandemia de COVID-19. CONCLUSIONES: La ERC en México presenta una alta carga de mortalidad y años de vida perdidos, pero contribuye poco a la discapacidad. Es esencial mejorar la detección temprana de la ERC, el acceso a tratamientos y la codificación de las causas de la enfermedad. Además, investigar las causas de la ERC de etiología desconocida, incluidos factores genéticos, es crucial para desarrollar tratamientos específicos en el futuro.

Role of KLHL3 and dietary K+ in regulating KS-WNK1 expression.

The physiological role of the shorter isoform of with no lysine kinase (WNK)1 that is exclusively expressed in the kidney (KS-WNK1), with particular abundance in the distal convoluted tubule, remains elusive. KS-WNK1, despite lacking the kinase domain, is nevertheless capable of stimulating the NaCl cotransporter, apparently through activation of WNK4. It has recently been shown that a less severe form of familial hyperkalemic hypertension featuring only hyperkalemia is caused by missense mutations in the WNK1 acidic domain that preferentially affect cullin 3 (CUL3)-Kelch-like protein 3 (KLHL3) E3-induced degradation of KS-WNK1 rather than that of full-length WNK1. Here, we show that full-length WNK1 is indeed less impacted by the CUL3-KLHL3 E3 ligase complex compared with KS-WNK1. We demonstrated that the unique 30-amino acid NH2-terminal fragment of KS-WNK1 is essential for its activating effect on the NaCl cotransporter and recognition by KLHL3. We identified specific amino acid residues in this region critical for the functional effect of KS-WNK1 and KLHL3 sensitivity. To further explore this, we generated KLHL3-R528H knockin mice that mimic human mutations causing familial hyperkalemic hypertension. These mice revealed that the KLHL3 mutation specifically increased expression of KS-WNK1 in the kidney. We also observed that in wild-type mice, the expression of KS-WNK1 was only detectable after exposure to a low-K+ diet. These findings provide new insights into the regulation and function of KS-WNK1 by the CUL3-KLHL3 complex in the distal convoluted tubule and indicate that this pathway is regulated by dietary K+ levels.NEW & NOTEWORTHY In this work, we demonstrated that the kidney-specific isoform of with no lysine kinase 1 (KS-WNK1) in the kidney is modulated by dietary K+ and activity of the ubiquitin ligase protein Kelch-like protein 3. We analyzed the role of different amino acid residues of KS-WNK1 in its activity against the NaCl cotransporter and sensitivity to Kelch-like protein 3.

Detection of Pulmonary Shunts by Transcranial Doppler in Hospitalized Non-mechanically Ventilated Coronavirus Disease-19 Patients.

In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated disease coronavirus disease 2019 (COVID-19), hypoxemia mechanisms differ from those observed in acute respiratory distress syndrome. Hypoxemia and respiratory failure in COVID- 19 are attributed to pulmonary angiopathy, increasing physiological pulmonary shunting1-3.

Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC.

Familial hyperkalemic hypertension (FHHt) can be mainly attributed to increased activity of the renal Na+:Cl- cotransporter (NCC), which is caused by altered expression and regulation of the with-no-lysine (K) 1 (WNK1) or WNK4 kinases. The WNK1 gene gives rise to a kidney-specific isoform that lacks the kinase domain (KS-WNK1), the expression of which occurs primarily in the distal convoluted tubule. The role played by KS-WNK1 in the modulation of the WNK/STE20-proline-alanine rich kinase (SPAK)/NCC pathway remains elusive. In the present study, we assessed the effect of human KS-WNK1 on NCC activity and on the WNK4-SPAK pathway. Microinjection of oocytes with human KS-WNK1 cRNA induces remarkable activation and phosphorylation of SPAK and NCC. The effect of KS-WNK1 was abrogated by eliminating a WNK-WNK-interacting domain and by a specific WNK inhibitor, WNK463, indicating that the activation of SPAK/NCC by KS-WNK1 is due to interaction with another WNK kinase. Under control conditions in oocytes, the activating serine 335 of the WNK4 T loop is not phosphorylated. In contrast, this serine becomes phosphorylated when the intracellular chloride concentration ([Cl-]i) is reduced or when KS-WNK1 is coexpressed with WNK4. KS-WNK1-mediated activation of WNK4 is not due to a decrease of the [Cl-]i. Coimmunoprecipitation analysis revealed that KS-WNK1 and WNK4 interact with each other and that WNK4 becomes autophosphorylated at serine 335 when it is associated with KS-WNK1. Together, these observations suggest that WNK4 becomes active in the presence of KS-WNK1, despite a constant [Cl-]i.

The European Eel NCCß Gene Encodes a Thiazide-resistant Na-Cl Cotransporter.

The thiazide-sensitive Na-Cl cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian distal convoluted tubule. NCC plays a key role in the regulation of blood pressure. Its inhibition with thiazides constitutes the primary baseline therapy for arterial hypertension. However, the thiazide-binding site in NCC is unknown. Mammals have only one gene encoding for NCC. The eel, however, contains a duplicate gene. NCCα is an ortholog of mammalian NCC and is expressed in the kidney. NCCß is present in the apical membrane of the rectum. Here we cloned and functionally characterized NCCß from the European eel. The cRNA encodes a 1043-amino acid membrane protein that, when expressed in Xenopus oocytes, functions as an Na-Cl cotransporter with two major characteristics, making it different from other known NCCs. First, eel NCCß is resistant to thiazides. Single-point mutagenesis supports that the absence of thiazide inhibition is, at least in part, due to the substitution of a conserved serine for a cysteine at position 379. Second, NCCß is not activated by low-chloride hypotonic stress, although the unique Ste20-related proline alanine-rich kinase (SPAK) binding site in the amino-terminal domain is conserved. Thus, NCCß exhibits significant functional differences from NCCs that could be helpful in defining several aspects of the structure-function relationship of this important cotransporter.

SPAK and OSR1 play essential roles in potassium homeostasis through actions on the distal convoluted tubule.

KEY POINTS: STE20 (Sterile 20)/SPS-1 related proline/alanine-rich kinase (SPAK) and oxidative stress-response kinase-1 (OSR1) phosphorylate and activate the renal Na(+) -K(+) -2Cl(-) cotransporter 2 (NKCC2) and Na(+) Cl(-) cotransporter (NCC). Mouse models suggest that OSR1 mainly activates NKCC2-mediated sodium transport along the thick ascending limb, while SPAK mainly activates NCC along the distal convoluted tubule, but the kinases may compensate for each other. We hypothesized that disruption of both kinases would lead to polyuria and severe salt-wasting, and generated SPAK/OSR1 double knockout mice to test this. Despite a lack of SPAK and OSR1, phosphorylated NKCC2 abundance was still high, suggesting the existence of an alternative activating kinase. Compensatory changes in SPAK/OSR1-independent phosphorylation sites on both NKCC2 and NCC and changes in sodium transport along the collecting duct were also observed. Potassium restriction revealed that SPAK and OSR1 play essential roles in the emerging model that NCC activation is central to sensing changes in plasma [K(+) ]. ABSTRACT: STE20 (Sterile 20)/SPS-1 related proline/alanine-rich kinase (SPAK) and oxidative stress-response kinase-1 (OSR1) activate the renal cation cotransporters Na(+) -K(+) -2Cl(-) cotransporter (NKCC2) and Na(+) -Cl(-) cotransporter (NCC) via phosphorylation. Knockout mouse models suggest that OSR1 mainly activates NKCC2, while SPAK mainly activates NCC, with possible cross-compensation. We tested the hypothesis that disrupting both kinases causes severe polyuria and salt-wasting by generating SPAK/OSR1 double knockout (DKO) mice. DKO mice displayed lower systolic blood pressure compared with SPAK knockout (SPAK-KO) mice, but displayed no severe phenotype even after dietary salt restriction. Phosphorylation of NKCC2 at SPAK/OSR1-dependent sites was lower than in SPAK-KO mice, but still significantly greater than in wild type mice. In the renal medulla, there was significant phosphorylation of NKCC2 at SPAK/OSR1-dependent sites despite a complete absence of SPAK and OSR1, suggesting the existence of an alternative activating kinase. The distal convoluted tubule has been proposed to sense plasma [K(+) ], with NCC activation serving as the primary effector pathway that modulates K(+) secretion, by metering sodium delivery to the collecting duct. Abundance of phosphorylated NCC (pNCC) is dramatically lower in SPAK-KO mice than in wild type mice, and the additional disruption of OSR1 further reduced pNCC. SPAK-KO and kidney-specific OSR1 single knockout mice maintained plasma [K(+) ] following dietary potassium restriction, but DKO mice developed severe hypokalaemia. Unlike mice lacking SPAK or OSR1 alone, DKO mice displayed an inability to phosphorylate NCC under these conditions. These data suggest that SPAK and OSR1 are essential components of the effector pathway that maintains plasma [K(+) ].

The regulation of Na+Cl- cotransporter by with-no-lysine kinase 4.

PURPOSE OF REVIEW: Abundant evidence supports that the NaCl cotransporter (NCC) activity is tightly regulated by the with-no-lysine (WNK) kinases. Here, we summarize the data regarding NCC regulation by WNKs, with a particular emphasis on WNK4. RECENT FINDINGS: Several studies involving in-vivo and in-vitro models have provided paradoxical data regarding WNK4 regulation of the NCC. Although some studies show that WNK4 can activate the NCC, other equally compelling studies show that WNK4 inhibits the NCC. Recent studies have shown that WNK4 is regulated by the intracellular chloride concentration ([Cl]i), which could account for these paradoxical results. In conditions of high [Cl]i, WNK4 could act as an inhibitor via heterodimer formation with other WNKs. In contrast, when [Cl]i is low, WNK4 can activate Ste20-related, proline-alanine-rich kinase (SPAK)/oxidative stress responsive kinase 1 (OSR1) and thus the NCC. Modulation of WNK4 by [Cl]i has been shown to account for the potassium-sensing properties of the distal convoluted tubule. Other regulators of WNK4 include hormones and ubiquitination. SUMMARY: Modulation of WNK4 activity by [Cl]i can account for its dual role on the NCC, and this has important physiological implications regarding the regulation of extracellular potassium concentration. Defective regulation of WNKs by ubiquitination explains most cases of familial hyperkalemic hypertension.

The Effect of WNK4 on the Na+-Cl- Cotransporter Is Modulated by Intracellular Chloride.

It is widely recognized that the phenotype of familial hyperkalemic hypertension is mainly a consequence of increased activity of the renal Na(+)-Cl(-) cotransporter (NCC) because of altered regulation by with no-lysine-kinase 1 (WNK1) or WNK4. The effect of WNK4 on NCC, however, has been controversial because both inhibition and activation have been reported. It has been recently shown that the long isoform of WNK1 (L-WNK1) is a chloride-sensitive kinase activated by a low Cl(-) concentration. Therefore, we hypothesized that WNK4 effects on NCC could be modulated by intracellular chloride concentration ([Cl(-)]i), and we tested this hypothesis in oocytes injected with NCC cRNA with or without WNK4 cRNA. At baseline in oocytes, [Cl(-)]i was near 50 mM, autophosphorylation of WNK4 was undetectable, and NCC activity was either decreased or unaffected by WNK4. A reduction of [Cl(-)]i, either by low chloride hypotonic stress or coinjection of oocytes with the solute carrier family 26 (anion exchanger)-member 9 (SLC26A9) cRNA, promoted WNK4 autophosphorylation and increased NCC-dependent Na(+) transport in a WNK4-dependent manner. Substitution of the leucine with phenylalanine at residue 322 of WNK4, homologous to the chloride-binding pocket in L-WNK1, converted WNK4 into a constitutively autophosphorylated kinase that activated NCC, even without chloride depletion. Elimination of the catalytic activity (D321A or D321K-K186D) or the autophosphorylation site (S335A) in mutant WNK4-L322F abrogated the positive effect on NCC. These observations suggest that WNK4 can exert differential effects on NCC, depending on the intracellular chloride concentration.

Impaired oxidative metabolism and calcium mishandling underlie cardiac dysfunction in a rat model of post-acute isoproterenol-induced cardiomyopathy.

Stress-induced cardiomyopathy, triggered by acute catecholamine discharge, is a syndrome characterized by transient, apical ballooning linked to acute heart failure and ventricular arrhythmias. Rats receiving an acute isoproterenol (ISO) overdose (OV) suffer cardiac apex ischemia-reperfusion damage and arrhythmia, and then undergo cardiac remodeling and dysfunction. Nevertheless, the subcellular mechanisms underlying cardiac dysfunction after acute damage subsides are not thoroughly understood. To address this question, Wistar rats received a single ISO injection (67 mg/kg). We found in vivo moderate systolic and diastolic dysfunction at 2 wk post-ISO-OV; however, systolic dysfunction recovered after 4 wk, while diastolic dysfunction worsened. At 2 wk post-ISO-OV, cardiac function was assessed ex vivo, while mitochondrial oxidative metabolism and stress were assessed in vitro, and Ca(2+) handling in ventricular myocytes. These were complemented with sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), and RyR2 expression studies. Ex vivo, basal mechanical performance index (MPI) and oxygen consumption rate (MVO2) were unchanged. Nevertheless, upon increase of metabolic demand, by ß-adrenergic stimulation (1-100 nM ISO), the MPI versus MVO2 relation decreased and shifted to the right, suggesting MPI and mitochondrial energy production uncoupling. Mitochondria showed decreased oxidative metabolism, membrane fragility, and enhanced oxidative stress. Myocytes presented systolic and diastolic Ca(2+) mishandling, and blunted response to ISO (100 nM), and all these without apparent changes in SERCA, PLB, or RyR2 expression. We suggest that post-ISO-OV mitochondrial dysfunction may underlie decreased cardiac contractility, mainly by depletion of ATP needed for myofilaments and Ca(2+) transport by SERCA, while exacerbated oxidative stress may enhance diastolic RyR2 activity.

[Structural functional and pathological aspects of the NaCl contransporter thiazide sensitive]. / Aspectos estructurales, funcionales y patológicos del cotransportador de NaCl sensible a tiazidas.

NCC cotransporter is the mayor pathway for sodium chloride reabsorption in the distal nephron and the target of thiazide diuretics which, given their clinical utility in the management of arterial hypertension, are amongst the top sold drugs in the world. NCC protein is of great physiological importance given its role in the maintenance of water and salt homeostasis on the organism. Inactivating mutations in the gene that codes for NCC cause Gitelman's syndrome: an autosomal recessive disease associated with arterial hypotension, metabolic alkalosis, hipokalemia and hypocalciuria. This syndrome represents strong evidence of the relevance of the role of NCC in blood pressure regulation, electrolyte and acid base balance. In this work we review the up to date knowledge regarding this cotransporter with special attention to the molecular aspects of the protein that determine is physiological function and pathological roles.

Sound waves and solutions: Point-of-care ultrasonography for acute kidney injury in cirrhosis.

This article delves into the intricate challenges of acute kidney injury (AKI) in cirrhosis, a condition fraught with high morbidity and mortality. The complexities arise from distinguishing between various causes of AKI, particularly hemodynamic AKI, in cirrhotic patients, who experience hemodynamic changes due to portal hypertension. The term "hepatocardiorenal syndrome" is introduced to encapsulate the intricate interplay among the liver, heart, and kidneys. The narrative emphasizes the often-overlooked aspect of cardiac function in AKI assessments in cirrhosis, unveiling the prevalence of cirrhotic cardiomyopathy marked by impaired diastolic function. The conventional empiric approach involving volume expansion and vasopressors for hepatorenal syndrome is critically analyzed, highlighting potential risks and variable patient responses. We advocate for a nuanced algorithm for AKI evaluation in cirrhosis, prominently featuring point-of-care ultrasonography (POCUS). POCUS applications encompass assessing fluid tolerance, detecting venous congestion, and evaluating cardiac function.

Portal Vein Doppler is a sensitive marker for evaluating venous congestion in End Stage Kidney Disease.

INTRODUCTION: Determining ultrafiltration volume in patients undergoing intermittent hemodialysis (IHD) is an essential component in the assessment and management of volume status. Venous Excess Ultrasound (VExUS) is a novel tool used to quantify the severity of venous congestion at the bedside. Given the high prevalence of pulmonary hypertension in patients with End Stage Kidney Disease (ESKD), venous Doppler could represent a useful tool to monitor decongestion in these patients. METHODS: This is a prospective observational study conducted in ESKD patients who were admitted to the hospital requiring IHD and Ultrafiltration. Inferior vena cava maximum diameter (IVCd), portal vein Doppler (PVD) and hepatic vein Doppler (HVD) were performed in all patients before and after a single IHD session. RESULTS: Forty-one patients were included. The prevalence of venous congestion was 88% based on IVCd and 63% based on portal vein pulsatility fraction (PVPF). Both mean IVCd and PVPF displayed a significant improvement after ultrafiltration. The percent decrease in PVPF was significantly larger than the percent decrease in IVCd. HVD alterations did not significantly improve after ultrafiltration. CONCLUSIONS: Our study revealed a high prevalence of venous congestion in hospitalized ESKD patients undergoing hemodialysis. After a single IHD session there was a significant improvement in both IVCd and PVPF. HVD showed no significant improvement with one IHD session. PVPF changes were more sensitive than IVCd changes during volume removal. This study suggests that, due to its rapid response to volume removal, PVD, among the various components of the venous excess ultrasound grading system, could be more effective in monitoring real-time decongestion in patients undergoing IHD.

Acute kidney injury and point-of-care ultrasound in liver cirrhosis: redefining hepatorenal syndrome.

Acute kidney injury (AKI) in patients with cirrhosis is a diagnostic challenge due to multiple and sometimes overlapping possible etiologies. Many times, diagnosis cannot be made based on case history, physical examination or laboratory data, especially when the nephrologist is faced with AKI with a hemodynamic basis, such as hepatorenal syndrome. In addition, the guidelines still include generalized recommendations regarding withdrawal of diuretics and plasma volume expansion with albumin for 48 h, which may be ineffective and counterproductive and may have iatrogenic effects, such as fluid overload and acute cardiogenic pulmonary edema. For this reason, the use of new tools, such as hemodynamic point-of-care ultrasound (PoCUS), allows us to phenotype volume status more accurately and ultimately guide medical treatment in a noninvasive, rapid and individualized manner.

Portal Vein Doppler tracks volume status in patients with severe tricuspid regurgitation: A Proof-of-Concept Study.

BACKGROUND: Renal and liver congestion are associated with adverse outcomes in patients with tricuspid regurgitation (TR). Currently, there are no valid sonographic indicators of fluid status in this population. Intra-renal venous Doppler (IRVD) is a novel method for quantifying renal congestion but its interpretation can be challenging in severe TR due to altered hemodynamics. This study explores the potential of portal vein Doppler (PVD) as an alternative marker for decongestion during volume removal in patients with severe TR. METHODS: 42 patients with severe TR undergoing decongestive therapy were prospectively enrolled. Inferior vena cava diameter (IVCd), PVD and IRVD were sequentially assessed during volume removal. Improvement criteria were Portal Vein Pulsatility Fraction (PVPF) < 70% and Renal Venous Stasis Index (RVSI) < 0.5 for partial improvement, and PVPF <30% and RVSI <0.2 for complete improvement. RESULTS: After volume removal, PVPF significantly improved from 130 ± 39% to 47 ± 44% (p < 0.001), while IRVD improved from 0.72 ± 0.08 to 0.54 ± 0.22 (p < 0.001). A higher proportion of patients displayed improvement in PVD compared to IRVD (partial: 38% vs. 29%, complete: 41% vs. 7%) (p < 0.001). IRVD only improved in patients with concomitant improvement in severe TR. PVD was the only predictor of achieving ≥5 litres of negative fluid balance (AUC 0.83 p = 0.001). CONCLUSIONS: This proof-of-concept study suggests that PVD is the only sonographic marker that can track volume removal in severe TR, offering a potential indicator for decongestion in this population. Further intervention trials are warranted to determine if PVD-guided decongestion improves patient outcomes in severe TR.

Dynamic changes of hepatic vein Doppler velocities predict preload responsiveness in mechanically ventilated critically ill patients.

BACKGROUND: Assessment of dynamic parameters to guide fluid administration is one of the mainstays of current resuscitation strategies. Each test has its own limitations, but passive leg raising (PLR) has emerged as one of the most versatile preload responsiveness tests. However, it requires real-time cardiac output (CO) measurement either through advanced monitoring devices, which are not routinely available, or echocardiography, which is not always feasible. Analysis of the hepatic vein Doppler waveform change, a simpler ultrasound-based assessment, during a dynamic test such as PLR could be useful in predicting preload responsiveness. The objective of this study was to assess the diagnostic accuracy of hepatic vein Doppler S and D-wave velocities during PLR as a predictor of preload responsiveness. METHODS: Prospective observational study conducted in two medical-surgical ICUs in Chile. Patients in circulatory failure and connected to controlled mechanical ventilation were included from August to December 2023. A baseline ultrasound assessment of cardiac function was performed. Then, simultaneously, ultrasound measurements of hepatic vein Doppler S and D waves and cardiac output by continuous pulse contour analysis device were performed during a PLR maneuver. RESULTS: Thirty-seven patients were analyzed. 63% of the patients were preload responsive defined by a 10% increase in CO after passive leg raising. A 20% increase in the maximum S wave velocity after PLR showed the best diagnostic accuracy with a sensitivity of 69.6% (49.1-84.4) and specificity of 92.8 (68.5-99.6) to detect preload responsiveness, with an area under curve of receiving operator characteristic (AUC-ROC) of 0.82 ± 0.07 (p = 0.001 vs. AUC-ROC of 0.5). D-wave velocities showed worse diagnostic accuracy. CONCLUSIONS: Hepatic vein Doppler assessment emerges as a novel complementary technique with adequate predictive capacity to identify preload responsiveness in patients in mechanical ventilation and circulatory failure. This technique could become valuable in scenarios of basic hemodynamic monitoring and when echocardiography is not feasible. Future studies should confirm these results.

Bedside Ultrasound in the Management of Cardiorenal Syndromes: An Updated Review.

BACKGROUND: Cardiorenal syndromes constitute a spectrum of disorders involving heart and kidney dysfunction modulated by a complex interplay of neurohormonal, inflammatory, and hemodynamic derangements. The management of such patients often poses a diagnostic and therapeutic challenge to physicians owing to gaps in understanding of pathophysiology, paucity of objective bedside diagnostic tools, and individual biases. SUMMARY: In this narrative review, we discuss the role of clinician who performed bedside ultrasound in the management of patients with cardiorenal syndromes. Novel sonographic applications such as venous excess ultrasound score (VExUS) are reviewed in addition to the lung and focused cardiac ultrasound. Further, underrecognized causes of heart failure such as high-flow arteriovenous fistula are discussed. KEY MESSAGE: Bedside ultrasound allows a comprehensive hemodynamic characterization of cardiorenal syndromes.

Doppler identified venous congestion in septic shock: protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS).

INTRODUCTION: Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. Venous congestion can be measured by Doppler ultrasound at the bedside through interrogation of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV) and intrarenal veins (IRV). The objective of this study is to quantify the association between Doppler identified venous congestion and the need for renal replacement therapy (RRT) or death for patients with septic shock. METHODS AND ANALYSIS: This study is a prespecified substudy of the ANDROMEDA-SHOCK 2 (AS-2) randomised control trial (RCT) assessing haemodynamic resuscitation in septic shock and will enrol at least 350 patients across multiple sites. We will include adult patients within 4 hours of fulfilling septic shock definition according to Sepsis-3 consensus conference. Using Doppler ultrasound, physicians will interrogate the IVC, HV, PV and IRV 6-12 hours after randomisation. Study investigators will provide web-based educational sessions to ultrasound operators and adjudicate image acquisition and interpretation. The primary outcome will be RRT or death within 28 days of septic shock. We will assess the hazard of RRT or death as a function of venous congestion using a Cox proportional hazards model. Sub-distribution HRs will describe the hazard of RRT given the competing risk of death. ETHICS AND DISSEMINATION: We obtained ethics approval for the AS-2 RCT, including this observational substudy, from local ethics boards at all participating sites. We will report the findings of this study through open-access publication, presentation at international conferences, a coordinated dissemination strategy by investigators through social media, and an open-access workshop series in multiple languages. TRIAL REGISTRATION NUMBER: NCT05057611.

Venous excess ultrasound score and acute kidney injury in patients with acute coronary syndrome.

AIMS: Systemic venous congestion is associated with an increased risk of acute kidney injury (AKI) in critically ill patients. Venous Excess Ultrasound Score (VExUS) has been proposed as a non-invasive score to assess systemic venous congestion. We aimed to evaluate the association between VExUS and AKI in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: This is a prospective study including patients with the diagnosis of ACS (both ST elevation and non-ST elevation ACS). VExUS was performed during the first 24 h of hospital stay. Patients were classified according to the presence of systemic congestion (VExUS 0/≥1). The primary objective of the study was to determine the occurrence of AKI, defined by KDIGO criteria. A total of 77 patients were included. After ultrasound assessment, 31 (40.2%) patients were categorized as VExUS ≥1. VExUS ≥1 was more frequently found in inferior vs. anterior myocardial infarction/non-ST-segment elevation acute myocardial infarction (48.3 vs. 25.8 and 22.5%, P = 0.031). At each increasing degree of VExUS, a higher proportion of patients developed AKI: VExUS = 0 (10.8%), VExUS = 1 (23.8%), VExUS = 2 (75.0%), and VExUS = 3 (100%; P < 0.001). A significant association between VExUS ≥1 and AKI was found [odds ratio (OR): 6.75, 95% confidence interval (CI): 2.21-23.7, P = 0.001]. After multivariable analysis, only VExUS ≥1 (OR: 6.15; 95% CI: 1.26-29.94, P = 0.02) remained significantly associated with AKI. CONCLUSION: In patients hospitalized with ACS, VExUS is associated with the occurrence of AKI. Further studies are needed to clarify the role of VExUS assessment in patients with ACS.