Regulation of Extracellular Sodium in End Stage Renal Disease Upon Volume and Electrolyte Challenges (RESERVE)

Regulation of Extracellular Sodium in End Stage Renal Disease Upon Volume and Electrolyte Challenges - a Prospective Trial.

Hyponatremia is the most common electrolyte disorder of all and can be observed in more than 30% of all patients in hospitals. Osmotic homeostasis of body fluids is essential for survival of all living creatures. It is widely accepted that extra- and intracellular osmolalities are in equilibrium at all times and thus, changes in the extracellular osmolality will lead to either shrinkage or swelling of cells which can be detrimental. In severe cases, it can lead to swelling of the brain and death. Even in less dramatic scenarios, symptoms such as epileptic seizures, headaches, depression and dizziness exist, leading to an increased risk of fractures, hospital admissions and a considerable burden for affected patients.

As short-term defense against osmotic stress, each individual cell is capable of actively externalizing or internalizing osmotically active solutes which restores normal or near-normal cell volume at the expense of an altered milieu interior. Obviously, there must be limitations to this strategy if intracellular integrity is meant to be kept stable. It has therefore been postulated that, apart from this cell-immanent mechanism, extracellular and intracellular electrolyte stores could assist in buffering osmotic imbalances.

The Edelman formula states that extracellular sodium is determined by the total amount of exchangeable body sodium (the major extracellular cation) plus potassium (the major intracellular cation) divided by total body water. Several studies have shown, that it only partially explains the changes in patients outside the osmotic equilibrium.

To better understand these physiological responses might not only promote the researcher's insight into the most basic cellular self-defense systems by measuring and comparing extra- and intracellular electrolyte concentrations with estimated changes in a patient that will be intravenously challenged with either water or sodium chloride 3%.

The evolution over time of extra- and intracellular sodium and other electrolytes will be assessed quantitatively in patients with impaired renal function after water or sodium chloride (NaCl) administration.

Study Overview

• Status: Recruiting
• Conditions: Hyponatremia
• Intervention / Treatment: Other: Water administration; Other: NaCl-Administration

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Volker Burst, MD; Phone Number: +49 221 478 86285; Email: volker.burst@uk-koeln.de
• Study Contact Backup: Name: Sadrija Cukoski, MD; Email: sadrija.cukoski@uk-koeln.de

Study Locations

• Germany
  • Cologne, Germany, 50937
    • Recruiting
    • Department II of Internal Medicine,University of Cologne
    • Contact: Volker Burst, MD; Phone Number: +49 221 478 86285; Email: volker.burst@uk-koeln.de
    • Contact: Cornelia Böhme; Phone Number: +49 221 478 97222; Email: cornelia.boehme@uk-koeln.de
    • Principal Investigator: Volker Burst, MD
    • Sub-Investigator: Sadrija Cukoski, MD
    • Sub-Investigator: Moritz Trappe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients ≥18 years
• Requirement of renal replacement therapy due to surgical (i.e., nephrectomy) or non-surgical (chronic kidney disease) reason
• Stable hemodialysis treatment for at least 3 months
• Urine output <100ml in 24 hours
• Glucose-corrected plasma sodium between 135 mmol/l and 145 mmol/l
• Plasma potassium between 3.5 mmol/l and 5 mmol/l
• Written informed consent

Exclusion Criteria:

• Peritoneal dialysis patients
• Signs of volume expansion or contraction
• Congestive heart failure (NYHA ≥2)
• acute illness (infection, congestive heart failure, liver cirrhosis, etc.) requiring hospital admission
• Uncontrolled arterial hypertension
• Hemoglobin ≤8g/dL
• Alcohol abuse
• Malnutrition
• Persons, who are in a dependency/employment relationship with the investigators
• Accommodation in an institution by judicial or administrative order

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Water-Group; Intravenous administration of water (Aqua ad injectabilia) until a decrease of plasma sodium of 5 to 8 mmol/l has been achieved	Other: Water administration; Intravenous administration of water (Aqua ad injectabilia) until a decrease of plasma sodium of 5 to 8 mmol/l has been achieved
Experimental: NaCl-Group; Intravenous administration of NaCl 3% until an increase of plasma sodium of 5 to 8 mmol/l has been achieved	Other: NaCl-Administration; Intravenous administration of NaCl 3% until an increase of plasma sodium of 5 to 8 mmol/l has been achieved

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
acute changes of extracellular osmolality	The primary aim is to compare the actual acute change of extracellular sodium with the estimated change of extracellular sodium in response to an intravenous challenge with either water or sodium. Precise evaluation of the validity of the concept of Edelman in acute changes of extracellular osmolality	300 minutes after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of extracellular electrolyte concentrations	extracellular electrolyte concentrations in response to an intravenous challenge with either water or sodium.	300 minutes after infusion
change of intracellular electrolyte concentrations	intracellular (red blood cells/white blood cells) electrolyte concentrations in response to an intravenous challenge with either water or sodium.	300 minutes after infusion
change of osmolality	change of osmolality in response to an intravenous challenge with either water or sodium	300 minutes after infusion
change of cell volume	cell volume (red blood cells) in response to an intravenous challenge with either water or sodium	300 minutes after infusion

Collaborators and Investigators

• Sponsor: University of Cologne
• Investigators: Principal Investigator: Volker Burst, MD, University Hospital of Cologne

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: May 3, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 9, 2024

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: hyponatremia; prospective trial; Water-Electrolyte Imbalance; intracellular measurements
• Additional Relevant MeSH Terms: Metabolic Diseases; Nutritional and Metabolic Diseases; Hyponatremia; Water-Electrolyte Imbalance
• Other Study ID Numbers: V1.2_2023-06-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No