Fluid Overload Management and Vascular Stiffness in Chronic Kidney Disease Patients With Hypertension

This study aims to reduce fluid overload in order to control blood pressure of hypertensive CKD patients using bio-impedance assessment of fluid status and using a diuretic therapy algorithm.

Study Overview

• Status: Terminated
• Conditions: Hypertension
• Intervention / Treatment: Other: Diuretic algorithm

Detailed Description

Hypertension is highly prevalent in individuals with chronic kidney disease (CKD). Gradual loss of kidney function is associated with sodium retention. This ultimately leads to fluid overload which has been associated with high blood pressure and heart failure in patients with CKD. In such cases, diuretics are prescribed to reduce fluid overload and thereby control blood pressure. In clinical practice, diuretics are mostly prescribed based on clinical assessment of fluid status (e.g. hypertension, shortness of breath, edema). Less often biomarkers are used like brain natriuretic peptide and bio-impedance spectroscopy. Nevertheless, uncontrolled hypertension is highly prevalent in CKD patients, and leads to accelerated decline in kidney function as well as to cardiovascular disease. Bio-impedance spectroscopy is an accurate tool to assess fluid overload in CKD patients. Accurate assessment of fluid overload and appropriate prescription of diuretics are two pivotal factors to control blood pressure ultimately leading to preservation of kidney function in patients with CKD and decreased cardiovascular risk. Fluid overload in CKD is well documented, however, there are no randomized controlled trials demonstrating that strict fluid overload control in CKD patients improves blood pressure and outcome. Therefore, this study aims to reduce fluid overload in order to control blood pressure of hypertensive CKD patients using bio-impedance assessment of fluid status and using a diuretic therapy algorithm. First, fluid status will be assessed in all study participants using bio-impedance spectroscopy. Second, the study participants will be divided into two groups; the control group which will initially receive standard conventional therapy (no intervention) for 6 months. In the intervention group, the treatment regimen will be adjusted using bio-impedance spectroscopy and a treatment algorithm for diuretic therapy. Medications will be adjusted for 3 months and patients will be followed up for another 3 months. After 6 months, the control group will be subjected to the fluid overload management strategy. The primary outcomes of the current study are improvement in, a) fluid status towards normovolemia, and b) blood pressure toward normotension. Secondary outcome is improvement in vascular health as assessed by pulse wave velocity and augmentation index. Altogether, an optimized fluid status via a fluid management plan will provide better control of fluid overload, blood pressure, and improvement in vascular health in CKD patients.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2P4
      • University of Alberta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult (>18 years old) outpatient with uncontrolled hypertension; defined as, AMBP ≥ 130/80 mmHg despite treatment
• With an estimated glomerular filtration rate (eGFR) of 15-45 ml/min/1.73 m2.
• Fluid overload of more than 5% of estimated normal ECFV, as assessed by Bio-impedance spectroscopy (we are using the Body Composition Monitor, a validated device marketed by Fresenius, Canada).

Exclusion Criteria:

• Pregnancy or lactation
• Declined informed consent
• Patients with cognitive dysfunction
• Surgery within six weeks of the study
• Patients with heart failure, atrial fibrillation, stroke, nephrotic syndrome and active auto-immune disease
• Patients with severe life-limiting comorbidities like cancer
• Patients with amputated limbs (despite the fact that the BCM device can be used if people have a unilateral amputation, the home devices measure via 2 legs).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; No intervention.
Experimental: Intervention group; Bio-impedance spectroscopy. Treatment algorithm for diuretic therapy.	Other: Diuretic algorithm; Implementing diuretic algorithm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluid status	Decrease in fluid status measured using bio-impedance spectroscopy	12 months
Blood pressure	Decrease in blood pressure	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular stiffness	Improvement in vascular health as assessed by augmentation index.	12 months

Collaborators and Investigators

• Sponsor: University of Alberta

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: April 1, 2022
• First Submitted That Met QC Criteria: May 12, 2022
• First Posted (Actual): May 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; Vascular Stiffness; Fluid Overload
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hypertension; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Natriuretic Agents; Diuretics
• Other Study ID Numbers: Pro00108113

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