Impact of Changes in Dialysis Sodium Concentration on Tissue Sodium Storage in Hemodialysis Patients
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Chronic Kidney Disease Requiring Chronic Dialysis
- Sponsor
- University of Erlangen-Nürnberg Medical School
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Tissue sodium content
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
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.
Investigators
Eligibility Criteria
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
Outcomes
Primary Outcomes
Tissue sodium content
Time Frame: 14 weeks
Tissue sodium content measured by 23Na MRI
Secondary Outcomes
- Lymphangiogenic profile(14 weeks)
- Flow-mediated vasodilatation (FMD)(14 weeks)
- Immune response to tissue Na+ accumulation(14 weeks)
- Pulse wave analysis and pulse wave velocity(14 weeks)
- Body fluid distribution (extracellular and intracellular water)(14 weeks)