Modulation of Tissue Sodium in Hemodialysis Patients

NCT03525223 | Completed

• 1 other identifier: DNa
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Kidney Disease Requiring Chronic Dialysis

Keywords

23Na MRI

Outcome Measures

Primary Outcomes (1)

• Tissue sodium content

  Tissue sodium content measured by 23Na MRI

  14 weeks

Secondary Outcomes (5)

• Lymphangiogenic profile

  14 weeks

• Body fluid distribution (extracellular and intracellular water)

  14 weeks

• Pulse wave analysis and pulse wave velocity

  14 weeks

• Flow-mediated vasodilatation (FMD)

  14 weeks

• Immune response to tissue Na+ accumulation

  14 weeks

Study Arms (2)

dialysate [Na+] 138 mmol/l

ACTIVE COMPARATOR

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+]

dialysate [Na+] 142 mmol/l

ACTIVE COMPARATOR

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+]

Interventions

Change of dialysate [Na+] PROCEDURE

Stepwise modulation of dialysate sodium concentration by 1-2 mmo/l per week

dialysate [Na+] 138 mmol/l; dialysate [Na+] 142 mmol/l

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (1)

Nephrology Department, University Hospital Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Related Publications (3)

• Dahlmann A, Dorfelt K, Eicher F, Linz P, Kopp C, Mossinger I, Horn S, Buschges-Seraphin B, Wabel P, Hammon M, Cavallaro A, Eckardt KU, Kotanko P, Levin NW, Johannes B, Uder M, Luft FC, Muller DN, Titze JM. Magnetic resonance-determined sodium removal from tissue stores in hemodialysis patients. Kidney Int. 2015 Feb;87(2):434-41. doi: 10.1038/ki.2014.269. Epub 2014 Aug 6.

  PMID: 25100048 BACKGROUND

• Kopp C, Linz P, Maier C, Wabel P, Hammon M, Nagel AM, Rosenhauer D, Horn S, Uder M, Luft FC, Titze J, Dahlmann A. Elevated tissue sodium deposition in patients with type 2 diabetes on hemodialysis detected by 23Na magnetic resonance imaging. Kidney Int. 2018 May;93(5):1191-1197. doi: 10.1016/j.kint.2017.11.021. Epub 2018 Feb 15.

  PMID: 29455909 BACKGROUND

• Titze J, Dahlmann A, Lerchl K, Kopp C, Rakova N, Schroder A, Luft FC. Spooky sodium balance. Kidney Int. 2014 Apr;85(4):759-67. doi: 10.1038/ki.2013.367. Epub 2013 Oct 9.

  PMID: 24107854 BACKGROUND

MeSH Terms

Interventions

Sodium

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Study Officials

• Christoph Kopp, MD

  Nephrology Department, University Erlangen, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2018
• First Posted: May 15, 2018
• Study Start: May 15, 2018
• Primary Completion: September 6, 2022
• Study Completion: September 6, 2022
• Last Updated: October 26, 2023

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)