Modulation of Tissue Sodium in Hemodialysis Patients
- Conditions
- Chronic Kidney Disease Requiring Chronic Dialysis
- Interventions
- Procedure: Change of dialysate [Na+]
- Registration Number
- NCT03525223
- Lead Sponsor
- University of Erlangen-Nürnberg Medical School
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 10
- Chronic Kidney Disease Stage 5D, hemodialysis performed for at least 6 months, three times hemodialysis per week, signed informed consent
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description dialysate [Na+] 138 mmol/l Change of dialysate [Na+] 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. dialysate [Na+] 142 mmol/l Change of dialysate [Na+] 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.
- Primary Outcome Measures
Name Time Method Tissue sodium content 14 weeks Tissue sodium content measured by 23Na MRI
- Secondary Outcome Measures
Name Time Method Lymphangiogenic profile 14 weeks Serum VEGF-C and sFLT4 levels will be determined
Flow-mediated vasodilatation (FMD) 14 weeks Measurement of vasodilatation and thereby arterial stiffness by a semi-automated ultrasound System (UNEXEF)
Immune response to tissue Na+ accumulation 14 weeks Blood monocytes will be isolated and their osmotic and inflammatory response will be determined
Pulse wave analysis and pulse wave velocity 14 weeks Change in central arterial pressure wave form and pulse wave velocity will be analyzed by SphygmoCor
Body fluid distribution (extracellular and intracellular water) 14 weeks Change in body fluid distribution will be assessed by body composition monitor (bioimpedance spectroscopy)
Trial Locations
- Locations (1)
Nephrology Department, University Hospital Erlangen
🇩🇪Erlangen, Bavaria, Germany