Clinical trial NCT02528448: 0,9% NaCl Effect on Kidney Function and Glycocalyx in Patients Operated on for Primary Hiparthrosis
Official title: The Effect of 0,9% NaCl on the Kidney Function, Vasoactive Hormones, Biomarkers and Glycosaminglycanes in Plasma in Patients Operated on for Primary Hiparthrosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Nephrotoxicity
Keywords: Vasoactive hormones
bio markers
salt regulation
Renal variables
Lead sponsor: Regional Hospital Holstebro
Sponsor class: OTHER
First posted: 2015-08-19
Enrollment: 40
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Urinary excretion of Neutrophil gelatinase-associated lipocalin
timeFrame: two days
Secondary outcomes:
measure: plasma Syndecan-1
timeFrame: two days
measure: plasma renin concentration
timeFrame: two days
measure: Urinary excretion of cyclic guanosine monophosphate
timeFrame: two days
measure: Urinary excretion of epithelial sodium channels
timeFrame: two days
measure: Urinary excretion of water channels
timeFrame: two days
measure: Plasma concentration of angiotensin 2
timeFrame: two days
measure: Plasma concentration of aldosterone
timeFrame: two days
measure: Plasma concentration of atrial natriuretic peptide (ANP)
timeFrame: two days
measure: Plasma concentration of brain natriuretic peptide (BNP)
timeFrame: two days
measure: Plasma concentration of cyclic guanosine monophosphate (cGMP)
timeFrame: two days
measure: Plasma concentration of endothelin
timeFrame: two days
measure: Plasma concentration of vasopressin (AVP, ADH)
timeFrame: two days
measure: Urinary excretion of Fatty acid-binding protein
timeFrame: two days
measure: Urinary excretion of Kidney Injury Molecule
timeFrame: two days
measure: Free water clearance
timeFrame: two days
measure: Plasma concentration of albumin
timeFrame: two days
measure: Plasma concentration of chloride
timeFrame: two days
measure: Plasma concentration of creatinine
timeFrame: two days
measure: Plasma osmolarity
timeFrame: two days
measure: Plasma concentration of sodium
timeFrame: two days
measure: Plasma concentration of potassium
timeFrame: two days
measure: Urinary excretion of creatinine
timeFrame: two days
measure: Urinary excretion of chloride
timeFrame: two days
measure: Urinary excretion of sodium
timeFrame: two days
measure: Urinary excretion of potassium
timeFrame: two days
measure: Fractional urinary sodium excretion
timeFrame: two days
measure: Urinary osmolarity
timeFrame: two days
measure: Urinary excretion of albumin
timeFrame: two days
measure: Urinary excretion of sodium-chloride symporter
timeFrame: two days
measure: pH
timeFrame: two days
measure: pulse
timeFrame: two days
measure: middle arterial pressure
timeFrame: two days
Other outcomes:
Locations:
city: Holstebro
country: Denmark
facility: Department of Medical Research, Regional Hospital Holstebro
Study officials:
affiliation: Regional Hospital Holstebro
name: Jesper N Bech, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Regional Hospital Holstebro
name: Erling B Perdersen, MD, DMSc
role: STUDY_DIRECTOR
affiliation: Regional Hospital Holstebro
name: Niels Peter Ekeløf, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.