Modulation of Tissue Sodium in Hemodialysis Patients

October 25, 2023 updated by: University of Erlangen-Nürnberg Medical School

Impact of Changes in Dialysis Sodium Concentration on Tissue Sodium Storage in Hemodialysis Patients

Salt (NaCl) intake is implicated in causing hypertension and cardiovascular disease, the commonest cause of death worldwide. The investigators recently established that Na+ is stored in tissues, bound to glycosaminoglycans (GAGs) in skin and muscle. The resulting local hypertonicity leads to immune cell-driven induction of local tissue electrolyte clearance via modulation of cutaneous lymph capillary density. To visualize these complex processes in man directly, the investigators established Na+ magnetic resonance imaging (23Na-MRI) and investigated Na+ stores in hemodialysis (HD) patients. Hemodialysis patients were sodium-"overloaded" and HD treatment lowered tissue Na+ stores in this study. The observed effects were highly variable and independent of Na+ or water removal from the body during a dialysis session. Tissue Na+ mobilization correlated with circulating vascular endothelial growth factor-C (VEGF-C). The investigators believe that excessive Na+ storage is a reversible condition and therefore susceptible for therapeutic interventions. The investigators hypothesize that lowering dialysate Na+ concentration may favorably affect accelerated tissue Na+ accumulation in hemodialysis patients. Besides, improved tissue Na+ storage, osmostress-induced as well as pro-inflammatory immune cell response should be affected by such a revised dialysis management.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

To evaluate effects of moderate reduction of dialysate Na+ concentration on tissue Na+ content the investigators intend to recruit 40 hemodialysis patients, who will be offered a therapeutic change of their dialysate Na+ concentration. After detection of tissue Na+ content using 23Na-MRI technique, the applied dialysate [Na+] will be initially increased stepwise by 2 mmol/l per week from 138 to 142 mmol/l and maintained for a period of 5 weeks. After another 23Na-MRI measurement, dialysate [Na+] will then be lowered stepwise by 1-2 mmol/l per week to a minimum of 135 mmol/l, which will be also maintained for a period of 5 weeks followed by a final 23Na-MRI assessment.

Hypothesis: Reduction of dialysate Na+ concentration will decrease tissue sodium storage.

Additionally, the investigators will assess changes in body fluid distribution by bioimpedance spectroscopy. Furthermore, vascular compliance in response to the modulation of dialysate [Na+] and its correlation with tissue Na+ will be assessed. To investigate the immune response to tissue Na+ accumulation, the osmostress-induced as well as pro-inflammatory immune cell response of isolated monocytes will be quantified.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Bavaria
      • Erlangen, Bavaria, Germany, 91054
        • Nephrology Department, University Hospital Erlangen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Chronic Kidney Disease Stage 5D, hemodialysis performed for at least 6 months, three times hemodialysis per week, signed informed consent

Exclusion Criteria:

  • Pregnancy, severe heart failure (NYHA III - IV), severe liver disease (CHILD C), acute infection, pacemaker or other non-MRI suitable conditions, hyponatremia < 132 mmol/l

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: dialysate [Na+] 138 mmol/l
Intervention: Change of dialysate [Na+] from 138 mmol/l to 142 mmol/l The dialysate [Na+] will be increased by 2 mmol/l per week and kept constant for 5 weeks (altogether 6 weeks). Before and after intervention tissue [Na+] will be determined by sodium MRI. Additionally body fluid distribution (by bioimpedance spectroscopy) and central arterial pressure wave form, pulse wave velocity as well as flow-mediated vasodilatation will be assessed.
Procedure: Change of dialysate [Na+]
Stepwise modulation of dialysate sodium concentration by 1-2 mmo/l per week
Active Comparator: dialysate [Na+] 142 mmol/l
Intervention: Change of dialysate [Na+] from 142 mmol/l to 135 mmol/l The dialysate [Na+] will be decreased by 2 mmol/l per week for 3 weeks and by 1mmol/l for 1 further week. Afterwards the dialysate [Na+] will be kept constant for 5 weeks (altogether 8 weeks). Before and after intervention tissue [Na+] will be determined by sodium MRI. Additionally body fluid distribution (by bioimpedance spectroscopy) and central arterial pressure wave form, pulse wave velocity as well as flow-mediated vasodilatation will be assessed.
Procedure: Change of dialysate [Na+]
Stepwise modulation of dialysate sodium concentration by 1-2 mmo/l per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tissue sodium content
Time Frame: 14 weeks
Tissue sodium content measured by 23Na MRI
14 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lymphangiogenic profile
Time Frame: 14 weeks
Serum VEGF-C and sFLT4 levels will be determined
14 weeks
Body fluid distribution (extracellular and intracellular water)
Time Frame: 14 weeks
Change in body fluid distribution will be assessed by body composition monitor (bioimpedance spectroscopy)
14 weeks
Pulse wave analysis and pulse wave velocity
Time Frame: 14 weeks
Change in central arterial pressure wave form and pulse wave velocity will be analyzed by SphygmoCor
14 weeks
Flow-mediated vasodilatation (FMD)
Time Frame: 14 weeks
Measurement of vasodilatation and thereby arterial stiffness by a semi-automated ultrasound System (UNEXEF)
14 weeks
Immune response to tissue Na+ accumulation
Time Frame: 14 weeks
Blood monocytes will be isolated and their osmotic and inflammatory response will be determined
14 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Erlangen-Nürnberg Medical School

Investigators

  • Principal Investigator: Christoph Kopp, MD, Nephrology Department, University Erlangen, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2018

Primary Completion (Actual)

September 6, 2022

Study Completion (Actual)

September 6, 2022

Study Registration Dates

First Submitted

April 24, 2018

First Submitted That Met QC Criteria

May 3, 2018

First Posted (Actual)

May 15, 2018

Study Record Updates

Last Update Posted (Actual)

October 26, 2023

Last Update Submitted That Met QC Criteria

October 25, 2023

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DNa

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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