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

Study Overview
=================
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.

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

Conditions
-----------------
Nephrotoxicity

Intervention / Treatment
-----------------
* Drug: Plasma-lyte
* Drug: 0,9% saline


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: plasma-lyte<br>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<br>* 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<br>* Other names: ATC: B 05 BB 01;|
| Active Comparator: 0,9% saline<br>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<br>* 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<br>* Other names: sodium chloride;|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vasoactive hormones, bio markers, salt regulation, Renal variables