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NCT Number: NCT06408077

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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department II of Internal Medicine,University of Cologne

Cologne, 50937, Germany

Location status: Recruiting

Location contact

Cornelia Böhme

CONTACT

[email protected]

+49 221 478 97222

Moritz Trappe

SUB_INVESTIGATOR

Sadrija Cukoski, MD

SUB_INVESTIGATOR

Volker Burst, MD

CONTACT

[email protected]

+49 221 478 86285

Volker Burst, MD

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Water administration

Other

Intravenous administration of water (Aqua ad injectabilia) until a decrease of plasma sodium of 5 to 8 mmol/l has been achieved

NaCl-Administration

Other

Intravenous administration of NaCl 3% until an increase of plasma sodium of 5 to 8 mmol/l has been achieved

Primary outcomes

  1. acute changes of extracellular osmolality

    Time frame: 300 minutes after infusion

    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

Secondary outcomes

  1. change of extracellular electrolyte concentrations

    Time frame: 300 minutes after infusion

    extracellular electrolyte concentrations in response to an intravenous challenge with either water or sodium.

  2. change of intracellular electrolyte concentrations

    Time frame: 300 minutes after infusion

    intracellular (red blood cells/white blood cells) electrolyte concentrations in response to an intravenous challenge with either water or sodium.

  3. change of osmolality

    Time frame: 300 minutes after infusion

    change of osmolality in response to an intravenous challenge with either water or sodium

  4. change of cell volume

    Time frame: 300 minutes after infusion

    cell volume (red blood cells) in response to an intravenous challenge with either water or sodium

Study contacts

Contact information is provided by the study sponsor or research team.

Sadrija Cukoski, MD

CONTACT

[email protected]

Volker Burst, MD

CONTACT

[email protected]

+49 221 478 86285

Sponsors and collaborators

Lead sponsor

University of Cologne

Other

Registry information

Official study title

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

Acronym: RESERVE

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
May 9, 2024
Registry last updated
Sep 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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