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

Overview

The objective of this prospective observational study is to determine the utility of ultrasonographic assessment using the VExUS protocol for dry weight adjustment in clinically euvolemic patients undergoing hemodialysis. The primary hypothesis is that the assessment of venous congestion by ultrasound may help identify patients who can tolerate increased ultrafiltration, thereby improving blood pressure control. The comparison group will consist of patients who do not meet the criteria for venous congestion according to the VExUS protocol. In patients meeting the criteria for venous congestion, the ultrafiltration volume during hemodialysis will be increased.

Patients receiving maintenance hemodialysis face persistent challenges in achieving optimal volume status, and intravascular congestion is a major contributor to cardiovascular morbidity. Traditional clinical signs have limited diagnostic accuracy for detecting volume excess, as noted in the protocol: "the evaluation of volume status based on classical symptoms and signs… has shown low sensitivity and specificity". Point-of-care ultrasonography (PoCUS) offers a non-invasive and reproducible method to assess congestion, yet the role of the VExUS protocol in guiding dry-weight adjustment has not been systematically evaluated in this population. This prospective, multicenter study incorporates a structured, repeated assessment of venous congestion over a five-week period. On the mid-week dialysis day, all participants undergo a modified VExUS examination (excluding intrarenal veins), lung ultrasound, and multifrequency bioimpedance. These assessments are repeated weekly for four consecutive weeks, enabling longitudinal characterization of venous congestion and its relationship with ultrafiltration tolerance, interdialytic weight gain, and blood pressure. Patients classified as congestive according to VExUS Doppler patterns receive a standardized ultrafiltration increase of 0.3 L during the following week, consistent with the protocol statement: "patients classified as congestive will have ultrafiltration increased… reducing dry weight by 0.3 kg during that week". Hemodynamic tolerance is monitored at each dialysis session, including intradialytic blood pressure, symptoms, and the need for nursing interventions. If the patient tolerates the increased ultrafiltration, the adjusted post-dialysis weight is incorporated into the prescribed dry weight. Patients without evidence of venous congestion continue with standard ultrafiltration based solely on interdialytic weight gain. The study also includes a comprehensive biomarker program. Baseline blood samples are collected on the first mid-week session and repeated at week five, measuring cardiac biomarkers (NT-proBNP, CA-125, troponin), markers of congestion (bioADM, sST2, CD146), and inflammatory mediators (FGF-23, IL-6, IL-18, TNF-α, among others). Samples requiring specialized analysis are processed and stored according to predefined procedures. These data will help explore biological correlates of venous congestion and their evolution during follow-up. Additional weekly assessments include lung ultrasound quantification of B-lines, bioimpedance-derived fluid status, and pre-dialysis blood pressure. Intradialytic parameters such as relative blood volume changes and hemodynamic tolerance are recorded at every session. At the end of follow-up, changes in prescribed dry weight, blood pressure, and antihypertensive therapy are evaluated. The primary objective is to determine whether VExUS can serve as a useful adjunct for dry-weight adjustment in hemodialysis patients. Secondary analyses will examine the impact of congestion-guided ultrafiltration on blood pressure, fluid status, and biomarker trajectories. All clinical decisions outside the predefined ultrafiltration adjustment follow routine practice, and the study does not introduce additional therapeutic interventions. This structured, repeated-measure design may help clarify the dynamic relationship between venous congestion, ultrafiltration tolerance, and volume management in hemodialysis, and inform future strategies for integrating PoCUS-based vascular assessment into standard nephrology care.