Usefulness of the VExUS Protocol for Dry-Weight Adjustment in Hemodialysis Patients: The Multicenter VExHD Study (VEX-HD)

Background

Patients undergoing hemodialysis (HD) have a markedly increased risk of cardiovascular mortality, particularly in the presence of volume overload. Increased preload promotes left ventricular (LV) hypertrophy and dysfunction, pulmonary vascular congestion, and diastolic dysfunction. Therefore, assessment of volume status represents a cornerstone of optimal HD management, and the accurate determination of dry weight is essential to prevent cardiovascular and hemodynamic complications.

Several approaches are available for volume status assessment, including clinical examination, biomarkers, and imaging techniques. However, the evaluation of volume status based on traditional signs and symptoms such as dyspnea, orthopnea, jugular venous distension, peripheral edema, hypertension, and pulmonary crackles has demonstrated limited sensitivity and specificity for the detection of intravascular volume overload. Likewise, the utility of conventional biomarkers for acute volume assessment in HD patients is limited because natriuretic peptides are substantially influenced by impaired renal function and underlying chronic cardiovascular disease.

Over the last decade, Point-of-Care Ultrasonography (PoCUS) has emerged as a valuable tool for congestion assessment owing to its non-invasive nature, wide availability, reproducibility, and absence of ionizing radiation. PoCUS-based evaluation of congestion encompasses three complementary approaches: assessment of tissue congestion through lung ultrasound (LUS), evaluation of systemic venous congestion using the Venous Excess Ultrasound Score (VExUS), and focused cardiac ultrasound (FoCUS) for the assessment of cardiac structure and function.

In this context, the Lung Water by Ultrasound-Guided Treatment (LUST) study demonstrated that LUS-guided ultrafiltration is an effective strategy for fluid management in HD patients. Nevertheless, the role of the VExUS protocol in the assessment of venous congestion among HD patients and its potential utility for dry-weight adjustment has not yet been systematically evaluated.

Study Objectives Primary Objective

To evaluate the utility of the Venous Excess Ultrasound Score (VExUS) protocol for dry-weight adjustment in patients receiving maintenance hemodialysis.

Secondary Objective

To assess the utility of the VExUS protocol in improving blood pressure control in patients undergoing maintenance hemodialysis.

Study Hypothesis

The use of the VExUS protocol may facilitate the identification of occult intravascular congestion in clinically euvolemic patients receiving maintenance hemodialysis.

Materials and Methods Study Design

This is a prospective, multicenter study conducted within the framework of routine clinical practice.

Before the midweek hemodialysis session (Wednesday or Thursday, depending on the patient's dialysis schedule), participants will undergo a modified VExUS ultrasound examination. Patients demonstrating evidence of intravascular congestion despite being clinically euvolemic will be identified. Clinical euvolemia will be defined as the absence of peripheral edema, jugular venous distension, pulmonary crackles, dyspnea, and orthopnea.

Patients classified as congested according to the modified VExUS protocol will undergo an increase in ultrafiltration prescription, corresponding to a standardized dry-weight reduction of 0.3 kg.

Study Population

Eligible participants will include adults aged ≥18 years receiving maintenance hemodialysis for at least 90 days in participating dialysis units and treated on a thrice-weekly schedule, provided that written informed consent is obtained.

Exclusion Criteria Clinical signs or symptoms of volume overload. Significant liver disease, including cirrhosis, hepatic steatosis, or portal vein thrombosis.

Severe tricuspid regurgitation. Inability to undergo adequate abdominal ultrasonographic examination (e.g., inability to perform breath-holding maneuvers or severe obesity).

Study Procedures Baseline Assessment

On the first study visit (midweek dialysis session), the following data will be collected:

Demographic and Clinical Variables Age and sex. Traditional cardiovascular risk factors (diabetes mellitus, hypertension, and dyslipidemia).

Cardiovascular comorbidities, including heart failure (with NYHA functional class), ischemic heart disease, peripheral arterial disease, arrhythmias, and previous stroke.

Etiology of chronic kidney disease. Residual urine output. Dialysis vintage. Type of vascular access. Dialysis modality. Dialysate conductivity. Dialysate temperature. Dialysate composition (citrate-, acetate-, or hydrochloric acid-based). Prescribed dry weight. Predialysis systolic and diastolic blood pressure (mean of the previous three dialysis sessions).

Antihypertensive treatment. Echocardiographic Parameters

The most recent transthoracic echocardiographic examination will be reviewed, including:

Left ventricular ejection fraction (LVEF). Left ventricular hypertrophy (LVH). E/e' ratio as a marker of diastolic dysfunction. Presence and severity of valvular heart disease. Laboratory Assessment

Routine laboratory measurements will include:

Complete blood count. Total serum proteins. Albumin. C-reactive protein. Ferritin. Transferrin saturation. Calcium. Phosphate. Intact parathyroid hormone. NT-proBNP. CA-125. Cardiac troponin.

Additional biomarkers of congestion and inflammation will be analyzed in a central laboratory, including:

bioADM. sST2. CD146. Copeptin. IGFBP-7. Klotho. FGF-23. Galectin-3. IL-33. IL-6. IL-18. IL-1β. TNF-α. IL1 receptor-like 1 (IL1RL1). Fatty acid-binding protein 4 (FABP4). GDF-15.

Serum samples will be centrifuged, frozen, and stored until shipment to the central laboratory at study completion.

Imaging and Hemodynamic Assessment

Before dialysis initiation, all participants will undergo:

Modified VExUS examination (excluding intrarenal venous Doppler assessment). Lung ultrasound according to the LUS protocol. Multifrequency bioimpedance spectroscopy (BCM®, Fresenius Medical Care, or equivalent device if unavailable).

Predialysis blood pressure measurement. Follow-up

Weekly assessments will be performed during four consecutive weeks before the midweek dialysis session and will include:

Modified VExUS examination. Lung ultrasound. Multifrequency bioimpedance spectroscopy. Predialysis blood pressure measurement.

At every dialysis session, the following parameters will be recorded:

Intradialytic blood pressure measurements. Hemodynamic tolerance. Interdialytic weight gain. Post-dialysis body weight. Relative blood volume decline measured by the blood-volume monitoring system.

At week 5, all baseline laboratory and biomarker assessments will be repeated.