Euvolemia-Based Assessment of Pulmonary Hypertension in Stable Hemodialysis Patients (EU-PHASE-HD)

Prospective Observational Study on Predictors and Types of Pulmonary Hypertension in Euvolemic Patients With End-Stage Kidney Disease on Maintenance Hemodialysis

Pulmonary hypertension (PH) is a frequent and clinically significant complication in patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis (HD). However, PH assessment in this population is often confounded by volume overload, leading to potential overestimation and misclassification.

This prospective, multicenter observational study aims to evaluate the prevalence, phenotype, and predictors of PH in HD patients under standardized euvolemic conditions. A structured pretrial phase including volume assessment and correction will be performed prior to echocardiographic evaluation, which will be conducted after confirmation of euvolemia, post-hemodialysis or on the following day.

In participants with echocardiographic findings suggestive of PH, right heart catheterization may be performed when clinically indicated and after obtaining specific informed consent.

The study integrates clinical, biological, dialysis-related, and echocardiographic data to provide a comprehensive characterization of PH in a well-defined ESKD population.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemodialysis; Hemodialysis Patients; Volume Assessment; End Stage Kidney Disease (ESRD); Volume Overload; Pulmonary Hypertension (PH)
• Intervention / Treatment: Other: Observational Assessment

Detailed Description

Pulmonary hypertension (PH), defined as mean pulmonary arterial pressure (mPAP) >20 mmHg, is increasingly recognized in patients with chronic kidney disease and is particularly prevalent in those with ESKD on maintenance HD.

Despite its prognostic importance, PH remains under-recognized and insufficiently characterized in HD patients. A major limitation of prior studies is the lack of standardized assessment of volume status, which significantly influences pulmonary pressures.

This prospective, multicenter cohort study aims to address this gap by evaluating PH after rigorous volume optimization. The study includes:

• A pretrial volume assessment phase (3 consecutive HD sessions)
• A structured volume correction phase (if needed)
• A main study cohort including only euvolemic patients
• An exploratory subgroup of patients with persistent hypervolemia

Euvolemia is defined using a multimodal approach including clinical examination, bioimpedance spectroscopy, inferior vena cava (IVC) diameter, interdialytic weight gain, blood pressure stability, and lung ultrasound criteria.

The primary objective is to determine the prevalence of PH in euvolemic HD patients. Secondary objectives include characterization of PH phenotypes and identification of clinical, dialysis-related, and echocardiographic predictors.

Right heart catheterization (RHC) is not mandated for all participants. In patients with echocardiographic findings suggestive of PHafter confirmation of euvolemia, RHC may be performed when clinically indicated and separately consented. When available, invasive hemodynamic data will be used to confirm PH and refine phenotype classification.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Stefan N Lujinschi, MD, PhD candidate; Phone Number: +40728102643; Email: stefanlujinschi@gmail.com

Study Locations

• Romania
  • Bucharest, Romania, 022328
    • Fundeni Clinical Institute
    • Contact: Stefan N Lujinschi, MD, PhD candidate; Phone Number: +40728102643; Email: stefanlujinschi@gmail.com
    • Principal Investigator: Stefan N Lujinschi, MD, PhD candidate
  • Bucharest, Romania, 022322
    • Institute for Cardiovascular Diseases C.C. Iliescu
    • Contact: Georgiana Olaru, MD; Phone Number: +40767805197; Email: dr.georgianaolaru@yahoo.com
    • Principal Investigator: Georgiana Olaru, MD
    • Sub-Investigator: Lucian M Predescu, Assist. Prof., MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with end-stage kidney disease (ESKD) receiving maintenance hemodialysis in two tertiary referral centers. Participants are consecutively enrolled and undergo structured volume assessment and optimization. The primary analysis includes patients who achieve predefined euvolemia criteria.

Description

Inclusion Criteria:

• Age ≥ 18 years.
• End-stage kidney disease on maintenance HD for ≥ 3 months.
• Stable clinical condition (no hospitalization in last 30 days).
• Able and willing to comply with study protocol.
• Provision of written informed consent

Exclusion Criteria:

• Moderate/severe left-sided valvular disease.
• Active pulmonary or cardiac decompensation.
• Persistent hypervolemia after completion of the volume assessment and correction phase
• Inability to undergo echocardiography or bioimpedance assessment.
• Acute infection or inflammatory condition at the time of enrollment.
• Inadequate echocardiographic window preventing reliable assessment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Euvolemic Hemodialysis Cohort; Participants with end-stage kidney disease on maintenance hemodialysis undergo a structured volume assessment (including clinical assessment, bioimpedance spectroscopy, inferior vena cava measurement, lung ultrasound and echocardiography) and, if necessary, a volume optimization phase. The primary study cohort includes patients who meet predefined euvolemia criteria. An exploratory subgroup includes patients with persistent hypervolemia, analyzed separately. Additional invasive evaluation, including right heart catheterization, may be performed only when clinically indicated and is not assigned as a study intervention.

Other: Observational Assessment; Participants undergo structured clinical, echocardiographic, and volume status assessments, including bioimpedance spectroscopy, lung ultrasound and inferior vena cava evaluation. Volume optimization measures are applied as part of routine clinical care and are not assigned as experimental interventions. Right heart catheterization may be performed in selected patients when clinically indicated and after specific informed consent, and is not considered a study intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Pulmonary Hypertension in Euvolemic Hemodialysis Patients	Pulmonary hypertension will be identified based on echocardiographic criteria (systolic pulmonary arterial pressure [sPAP] ≥40 mmHg) after confirmation of euvolemia. In participants undergoing clinically indicated right heart catheterization, invasive hemodynamic data (mean pulmonary arterial pressure [mPAP] ≥20 mmHg) will be used for confirmation of pulmonary hypertension.	At baseline echocardiographic evaluation after confirmation of euvolemia (within 1 week, post-hemodialysis or next day); in participants undergoing clinically indicated right heart catheterization, assessment may occur within 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Hypertension Phenotype Distribution	Distribution of pulmonary hypertension phenotypes based on echocardiographic assessment in the overall cohort, with definitive classification based on right heart catheterization in patients undergoing clinically indicated invasive evaluation.	At baseline echocardiography after euvolemia (within 1 week, post-hemodialysis or next day); in participants with clinically indicated right heart catheterization, assessment may occur within 3 months
Predictors of Pulmonary Hypertension	Clinical, laboratory, dialysis-related, vascular access-related, and volume-related variables associated with the presence of pulmonary hypertension	At baseline evaluation
Association Between Vascular Access and Pulmonary Hypertension	Relationship between vascular access type and pulmonary hypertension parameters.	At baseline evaluation
Association Between Volume Status and Pulmonary Hypertension	Association between bioimpedance, inferior vena cava diameter, interdialytic weight gain, and pulmonary hypertension.	At baseline evaluation
Blood Pressure Variability and Pulmonary Hypertension	Relationship between intradialytic blood pressure variability and pulmonary hypertension parameters.	At baseline evaluation

Collaborators and Investigators

• Sponsor: Stefan Lujinschi
• Collaborators: Carol Davila University of Medicine and Pharmacy; Institutul Clinic Fundeni; Institutul de Urgenţă pentru Boli Cardiovasculare Prof.Dr. C.C. Iliescu
• Investigators: Study Chair: Gener Ismail, Professor, MD, PhD, Fundeni Clinical Institute; Principal Investigator: Georgiana N Olaru, MD, Institute for Cardiovascular Diseases C.C. Iliescu; Study Chair: Ioan M Coman, Professor, MD, PhD, Institute for Cardiovascular Diseases C.C. Iliescu

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): June 30, 2026

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Echocardiography; Hemodialysis; Vascular Access; Euvolemia; End-Stage Kidney Disease; Interdialytic Weight Gain; Volume Status; Blood Pressure Variability; Lung Ultrasound; Volume Overload; Bioimpedance Spectroscopy
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Hypertension; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Kidney Failure, Chronic; Hypertension, Pulmonary; Edema
• Other Study ID Numbers: 12798 (Other Identifier: Fundeni Clinical Institute - Ethics Committee); EU-PHASE-HD-01 (Other Identifier: Fundeni Clinical Institute - Adult Nephrology Department)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No