Modulation of Tissue Sodium in Hemodialysis Patients

Chronic Kidney Disease Requiring Chronic Dialysis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03525223
• Other study ID #: DNa
• Status: Completed
• Phase: N/A
• Start date: May 15, 2018
• Est. completion date: September 6, 2022

Study information

• Verified date: November 2020
• Source: University of Erlangen-Nürnberg Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 6, 2022
• Est. primary completion date: September 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Disease Requiring Chronic Dialysis
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Procedure:
• Change of dialysate [Na+]
Stepwise modulation of dialysate sodium concentration by 1-2 mmo/l per week

Locations

Country	Name	City	State
Germany	Nephrology Department, University Hospital Erlangen	Erlangen	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tissue sodium content	Tissue sodium content measured by 23Na MRI	14 weeks
Secondary	Lymphangiogenic profile	Serum VEGF-C and sFLT4 levels will be determined	14 weeks
Secondary	Body fluid distribution (extracellular and intracellular water)	Change in body fluid distribution will be assessed by body composition monitor (bioimpedance spectroscopy)	14 weeks
Secondary	Pulse wave analysis and pulse wave velocity	Change in central arterial pressure wave form and pulse wave velocity will be analyzed by SphygmoCor	14 weeks
Secondary	Flow-mediated vasodilatation (FMD)	Measurement of vasodilatation and thereby arterial stiffness by a semi-automated ultrasound System (UNEXEF)	14 weeks
Secondary	Immune response to tissue Na+ accumulation	Blood monocytes will be isolated and their osmotic and inflammatory response will be determined	14 weeks