0,9% NaCl Effect on Kidney Function and Glycocalyx in Patients Operated on for Primary Hiparthrosis (KIPA)

The Effect of 0,9% NaCl on the Kidney Function, Vasoactive Hormones, Biomarkers and Glycosaminglycanes in Plasma in Patients Operated on for Primary Hiparthrosis

The purpose of this study is to determine if chloride is nephrotoxic using 0,9% saline versus Plasma-Lytein in patients having primary hip replacement surgery. The outcome is found measuring bio markers, vasoactive hormones and salt regulation. And to measure syndecan as a marker for glycocalyx degradation.

Study Overview

• Status: Unknown
• Conditions: Nephrotoxicity
• Intervention / Treatment: Drug: Plasma-lyte; Drug: 0,9% saline

Detailed Description

Hypothesis:

Chloride has a nephrotoxic effect, which can be shown partially by measuring bio markers for tubular injury in urine, partially by the changes in tubular transport of sodium and water in different parts of the nephron. This can be demonstrated using isotone sodium solutions with a lower chloride concentration in this study plasma-lyte versus normal isotone saline.

Klorid has a toxic effect on the glycocalyx layer and leads to a rise in syndecan 1 and simultaneously a change in Salt Blood Test either by a direct simulation and ANP levels in plasma or as a consequence of the hyperchloremic acidosis. This can be demonstrated using isotone sodium solutions with a lower chloride concentration in this study plasma-lyte versus normal isotone saline.

Purpose:

The purpose is to observe changes in bio markers, vasoactive hormones and salt regulation in patients randomized to either 0,9% saline or plasma-lyte undergoing primary uncemented hip replacement surgery.

Design:

40 patients undergoing primary uncemented hip replacement surgery will be randomized to either 0,9% saline or plasma-lyte for standard fluid resuscitation and blood loss replacement in this controlled and double blinded study. The patients will deliver a 24 hour urine sample before surgery and approximately 10 days after. From the start of the surgery and to the day after all urine will be collected and blood samples will be taken.

Perspective:

If chloride is found to be nephrotoxic it could lead to a general change in fluid resuscitation recommendations in critically ill patient, patients with kidney disease and patients undergoing surgery. It will also expand our knowledge about the permeability of the blood vessels.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Holstebro, Denmark, 7500
    • Recruiting
    • Department of Medical Research, Regional Hospital Holstebro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Indication for uncemented primary hiparthroplasty
• age < 60

Exclusion Criteria:

• Blooddonation or transfusion during the last month
• Not willing to participate
• estimated GFR below 30ml/min
• type 1 diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: plasma-lyte; Continuous 1 hour infusion of plasma-lyte 15 micrograms/kg/hour for the first hour then 5 micrograms/kg/hour + amount needet for blood replacement	Drug: Plasma-lyte; Continuous 1 hour infusion of plasma-lyte 15 micrograms/kg/hour for the first hour then 5 micrograms/kg/hour + amount needet for blood replacement; Other Names: ATC: B 05 BB 01
Active Comparator: 0,9% saline; Continuous 1 hour infusion of 0,9% saline15 micrograms/kg/hour for the first hour then 5 micrograms/kg/hour + amount needet for blood replacement	Drug: 0,9% saline; Continuous 1 hour infusion of 0,9% saline 15 micrograms/kg/hour for the first hour then 5 micrograms/kg/hour + amount needet for blood replacement; Other Names: sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Urinary excretion of Neutrophil gelatinase-associated lipocalin	two days

Secondary Outcome Measures

Outcome Measure	Time Frame
plasma Syndecan-1	two days
plasma renin concentration	two days
Urinary excretion of cyclic guanosine monophosphate	two days
Urinary excretion of epithelial sodium channels	two days
Urinary excretion of water channels	two days
Plasma concentration of angiotensin 2	two days
Plasma concentration of aldosterone	two days
Plasma concentration of atrial natriuretic peptide (ANP)	two days
Plasma concentration of brain natriuretic peptide (BNP)	two days
Plasma concentration of cyclic guanosine monophosphate (cGMP)	two days
Plasma concentration of endothelin	two days
Plasma concentration of vasopressin (AVP, ADH)	two days
Urinary excretion of Fatty acid-binding protein	two days
Urinary excretion of Kidney Injury Molecule	two days
Free water clearance	two days
Plasma concentration of albumin	two days
Plasma concentration of chloride	two days
Plasma concentration of creatinine	two days
Plasma osmolarity	two days
Plasma concentration of sodium	two days
Plasma concentration of potassium	two days
Urinary excretion of creatinine	two days
Urinary excretion of chloride	two days
Urinary excretion of sodium	two days
Urinary excretion of potassium	two days
Fractional urinary sodium excretion	two days
Urinary osmolarity	two days
Urinary excretion of albumin	two days
Urinary excretion of sodium-chloride symporter	two days
pH	two days
pulse	two days
middle arterial pressure	two days

Collaborators and Investigators

• Sponsor: Regional Hospital Holstebro
• Investigators: Principal Investigator: Jesper N Bech, MD, PhD, Regional Hospital Holstebro; Study Director: Erling B Perdersen, MD, DMSc, Regional Hospital Holstebro; Principal Investigator: Niels Peter Ekeløf, MD, PhD, Regional Hospital Holstebro

Publications and helpful links

General Publications

• Ostergaard AM, Jorgensen AN, Bovling S, Ekelof NP, Mose FH, Bech JN. Effect of 0.9% NaCl compared to plasma-lyte on biomarkers of kidney injury, sodium excretion and tubular transport proteins in patients undergoing primary uncemented hip replacement - a randomized trial. BMC Nephrol. 2021 Mar 26;22(1):111. doi: 10.1186/s12882-021-02310-4.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): February 1, 2016

Study Registration Dates

• First Submitted: August 17, 2015
• First Submitted That Met QC Criteria: August 18, 2015
• First Posted (Estimate): August 19, 2015

Study Record Updates

• Last Update Posted (Estimate): August 19, 2015
• Last Update Submitted That Met QC Criteria: August 18, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Renal variables; Vasoactive hormones; bio markers; salt regulation
• Additional Relevant MeSH Terms: Pharmaceutical Solutions; Ophthalmic Solutions; Plasma-lyte 148
• Other Study ID Numbers: NPE-01-2014