Can Changes in Dialysate Sodium Concentration Improve Blood Pressure and Endothelial Function in Chronic HD Patients?

NCT07459348 | Not Yet Recruiting

• 1 other identifier: 1-10-72-19-26
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

People with end stage kidney disease cannot regulate salt and water normally, which often leads to high blood pressure, fluid overload, and a higher risk of heart disease. Hemodialysis is a life sustaining treatment that removes waste products, excess fluid, and electrolytes from the blood. However, the treatment itself can influence blood pressure and how the blood vessels function. Many patients experience symptoms such as thirst, headaches, fatigue, and swelling, which affect both daily well being and long term health. One possible way to reduce these problems may be as simple as adjusting the amount of sodium in the dialysis fluid. During dialysis, substances move between the patient's blood and the dialysate, the special fluid used in the machine. Sodium is one of the most important components because it helps regulate fluid balance and blood pressure. A higher sodium concentration in the dialysate can make patients feel more thirsty, cause them to drink more, and lead to fluid retention and higher blood pressure. On the other hand, lowering sodium too much can cause dizziness, low blood pressure, cramps, and discomfort during treatment. Because of this, there is ongoing debate about what the "right" sodium level should be. Too much sodium over time may also harm the blood vessels. The inner lining of the vessels, called the endothelium, is protected by a thin layer known as the glycocalyx. This layer helps prevent sodium from entering the vessel wall and supports the production of nitric oxide, a molecule that relaxes blood vessels and reduces inflammation. High salt exposure can damage the glycocalyx and reduce nitric oxide production, making the vessels stiffer and raising blood pressure. In dialysis patients, low nitric oxide levels are linked to worse outcomes and episodes of rising blood pressure during treatment. Some small studies suggest that lowering dialysate sodium can improve blood pressure and endothelial function, but larger studies have not shown clear effects on survival. This indicates that we still do not fully understand which patients benefit most or how sodium changes affect both physical and subjective symptoms. This study aims to fill these knowledge gaps by examining how a lower sodium concentration in the dialysate affects blood pressure, blood vessel function, fluid overload, inflammation, and patient reported symptoms. The goal is to provide new insights that could help tailor dialysis treatment to individual patients in a simple and cost effective way. The study will compare two sodium concentrations: a lower level (133 mmol/L) and the standard level used in many clinics (139 mmol/L). Twenty five patients receiving chronic in center hemodialysis will participate. Each patient will undergo both treatments for three weeks each, in random order, with a two week washout period in between. This crossover design allows each patient to serve as their own control, making it easier to detect meaningful differences. The main outcome is the difference in 24 hour systolic blood pressure between the two sodium levels. Secondary outcomes include changes in nitric oxide levels in the blood, measures of fluid overload using two different techniques, markers of inflammation, arterial stiffness, and patient reported symptoms such as thirst, fatigue, and overall well being. The study will also compare two methods for assessing fluid overload: bioimpedance spectroscopy and a newer carbon monoxide rebreathing technique. Blood pressure and arterial stiffness will be measured over 44 hours using a portable device. Blood samples will be collected to analyze nitric oxide, inflammatory markers, and sodium handling in red blood cells. Fluid status will be measured using both bioimpedance and the CO rebreathing method. Patients will complete a weekly questionnaire developed together with dialysis patients to capture their experiences and symptoms.

Conditions

Dialysis Dependent Chronic Kidney Disease; Dialysis Patients; Sodium Excess; High Blood Pressure

Keywords

Dialysate Sodium Concentration; Hemodialysis; Blood Pressure Control; Endothelial Function / Nitric Oxide (NOx); Fluid Overload Assessment (CO Rebreathing & Bioimpedance)

Outcome Measures

Primary Outcomes (1)

• 24h systolic blood pressure

  Change in systolic 24-hour ambulatory blood pressure measured at the end of each 3-week intervention period (low-sodium dialysate vs. standard-sodium dialysate). Each participant undergoes 44-hour ambulatory blood pressure monitoring at the end of both periods, and the primary comparison is the within-participant difference between the two dialysate sodium concentrations. Unit of Measure: mmHg

  Day 19 in each intervention period

Secondary Outcomes (10)

• Diastolic 24-hour ambulatory blood pressure

  Day 19 in each intervention period

• Pulse wave velocity (arterial stiffness)

  Day 19 in each intervention period

• Salt Blood Test

  Day 19 in each intervention period

• Plasma nitric oxide metabolites (NOx)

  Day 19 of each intervention period

• Inflammatory cytokines

  Day 19 of each intervention period

Study Arms (2)

Low-Sodium Dialysate First (Crossover Sequence 1)

EXPERIMENTAL

Participants receive low-sodium dialysate (133 mmol/L) for 3 weeks, followed by standard-sodium dialysate (139 mmol/L) after a 2-3 week washout.

Device: Low-Sodium Dialysate (133 mmol/L); Device: Standard-Sodium Dialysate (139 mmol/L)

tandard-Sodium Dialysate First (Crossover Sequence 2)

EXPERIMENTAL

Participants receive standard-sodium dialysate (139 mmol/L) for 3 weeks, followed by low-sodium dialysate (133 mmol/L) after a 2-3 week washout.

Device: Low-Sodium Dialysate (133 mmol/L); Device: Standard-Sodium Dialysate (139 mmol/L)

Interventions

Low-Sodium Dialysate (133 mmol/L) DEVICE

Hemodialysis performed with dialysate sodium concentration of 133 mmol/L.

Also known as: Intervention 1

Low-Sodium Dialysate First (Crossover Sequence 1); tandard-Sodium Dialysate First (Crossover Sequence 2)

Standard-Sodium Dialysate (139 mmol/L) DEVICE

Hemodialysis performed with dialysate sodium concentration of 139 mmol/L.

Also known as: Intervention 2

Low-Sodium Dialysate First (Crossover Sequence 1); tandard-Sodium Dialysate First (Crossover Sequence 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults receiving chronic in-center hemodialysis at Regional Hospital Gødstrup
• Age ≥ 18 years
• On thrice-weekly hemodialysis for a stable period (as assessed in EPJ)
• Plasma sodium within the range required for safe participation (as per screening)
• Able to understand study information and provide written informed consent
• Eligible based on review of electronic patient record (dialysis duration, frequency, age, p-sodium)

You may not qualify if:

• Significant cardiac disease that may interfere with participation, including:
• Heart failure (with clinically relevant instability)
• Recent acute myocardial infarction (date verified in EPJ)
• Pacemaker (specific types that interfere with measurements)
• History of stroke or TCI (date verified in EPJ)
• Amputation of an extremity (affects body composition measurements)
• Diabetes with unstable glycemic control or recent major treatment changes
• Any condition that prevents accurate blood pressure measurement or CO-rebreathing
• Inability to complete study procedures (questionnaires, monitoring, blood sampling)
• Expected inability to complete both intervention periods (e.g., planned transfer, transplantation)
• Declines participation after receiving oral and written information

Sponsors & Collaborators

• Gødstrup Hospital: lead

Study Sites (1)

Gødstrup Hospital

Herning, 7400, Denmark

Location

Related Publications (17)

• Flythe JE,Chang TI,Gallagher MP,Lindley E,Madero M,Sarafidis PA,Unruh ML,Wang AY,Weiner DE,Cheung M,Jadoul M,Winkelmayer WC,Polkinghorne KR,Conference Participants

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• Iatridi F,Malandris K,Ekart R,Xagas E,Karpetas A,Theodorakopoulou MP,Karagiannidis A,Georgiou A,Papagianni A,Sarafidis P

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• Reitsma S,Slaaf DW,Vink H,van Zandvoort MA,oude Egbrink MG

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• Oberleithner H,Peters W,Kusche-Vihrog K,Korte S,Schillers H,Kliche K,Oberleithner K

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• Oberleithner H,Riethmüller C,Schillers H,MacGregor GA,de Wardener HE,Hausberg M

  BACKGROUND

• Zhou YL, Liu J, Ma LJ, Sun F, Shen Y, Huang J, Cui TG. Effects of increasing diffusive sodium removal on blood pressure control in hemodialysis patients with optimal dry weight. Blood Purif. 2013;35(1-3):209-15. doi: 10.1159/000346631. Epub 2013 Mar 19.

  PMID: 23548637 BACKGROUND

• Macunluoglu B, Gumrukcuoglu HA, Atakan A, Demir H, Alp HH, Akyol A, Akdag S, Yavuz A, Eren Z, Keskin S, Ari E. Lowering dialysate sodium improves systemic oxidative stress in maintenance hemodialysis patients. Int Urol Nephrol. 2016 Oct;48(10):1699-704. doi: 10.1007/s11255-016-1367-z. Epub 2016 Jul 29.

  PMID: 27473155 BACKGROUND

• Konukoglu D, Uzun H. Endothelial Dysfunction and Hypertension. Adv Exp Med Biol. 2017;956:511-540. doi: 10.1007/5584_2016_90.

  PMID: 28035582 BACKGROUND

• Georgianos PI, Agarwal R. Epidemiology, diagnosis and management of hypertension among patients on chronic dialysis. Nat Rev Nephrol. 2016 Oct;12(10):636-47. doi: 10.1038/nrneph.2016.129. Epub 2016 Aug 30.

  PMID: 27573731 BACKGROUND

• Fischereder M, Michalke B, Schmockel E, Habicht A, Kunisch R, Pavelic I, Szabados B, Schonermarck U, Nelson PJ, Stangl M. Sodium storage in human tissues is mediated by glycosaminoglycan expression. Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F319-F325. doi: 10.1152/ajprenal.00703.2016. Epub 2017 Apr 26.

  PMID: 28446462 BACKGROUND

• Elattaby GH, Kora MA, Emara MM, El-Khair NTA, Kasem HE. Nitric Oxide Levels as a Marker of Intradialytic Hypertension in End-Stage Renal Disease Patients. Saudi J Kidney Dis Transpl. 2023 Mar 1;34(2):134-141. doi: 10.4103/1319-2442.391891. Epub 2023 Dec 25.

  PMID: 38146722 BACKGROUND

MeSH Terms

Conditions

Hypernatremia; Hypertension

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Jesper N Bech, Consultant, Professor

  University Clinic in Nephrology and Hypertension

  STUDY DIRECTOR

Central Study Contacts

Bodil G Hornstrup, MD, PhD

CONTACT

004578431398; bodil.hornstrup@rm.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a randomized, crossover, single blinded interventional trial in which each participant receives both interventions-dialysis with low and standard sodium concentration-in two consecutive 3 week periods. Participants are blinded, while dialysis nurses and investigators are unblinded. Interventions: * Low sodium concentration: 133 mmol/L * Standard sodium concentration: 139 mmol/L The sequence is determined by randomization. After the first 3 week period, participants cross over to the opposite intervention following a 2 to 3 week washout period.

Study Record Dates

• First Submitted: March 4, 2026
• First Posted: March 9, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: From publication (date unknown) untill 5 years after publication.
• Access Criteria: De-identified individual participant data underlying the results reported in this study will be available to researchers upon reasonable request to the corresponding author after publication. Data will be shared with researchers who provide a methodologically sound proposal and whose proposed use aligns with the aims of the approved project. Access may require a data sharing agreement in accordance with institutional and ethical regulations. Details regarding which data will be shared and the method of access will be arranged between the corresponding author and the requesting researcher.

Locations

DK (1)