Hydroxyethyl Starch and Renal Function After Hip Replacement Surgery

Study Overview
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Brief Summary
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The purpose of this project is to investigate if hydroxyethyl starch (HES) is potential nephrotoxic and examine the effects on the circulation and kidneys during administration of HES during surgery.

Detailed Description
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Hydroxyethyl starch (HES) is widely used in hospitals to maintain circulation in critically ill patients. In recent years studies have raised suspicion that HES is nephrotoxic. So far acute kidney injury has been diagnosed based on creatinine measurements, but new technology allows for earlier diagnosis using measurements of biomarkers in urine. The purpose of this project is to investigate HES's potential toxicity and effects on the circulation and kidneys using measurements of biomarkers specific for toxicity and for the sodium/water balance in the urine and by measurements of vasoactive hormones in the blood after administration of HES 130/0.4

Official Title
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Effect of Hydroxyethyl Starch on Renal Handling of Sodium and Water, Vasoactive Hormones,Biomarkers and the Circulatory System in Patients Undergoing Hip Replacement Surgery

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: Voluven (Hydroxyethyl starch 130/0,4)
* Drug: Sodium Chloride 9 mg/ml


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Males and females Indication for Arthroplasty of hip Exclusion Criteria: Blood donation within the last month Lack of wish to participate eGFR< 15ml/min pregnancy or breast feeding Need of NSAID

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Voluven (Hydroxyethyl starch 130/0,4)<br>Patients undergoing hip replacement surgery will receive either fluid therapy with active comparator (Voluven) or placebo (Sodium Chloride. Patients will receive minimum 7,5 ml/kg in the first hour of the surgery and 5 ml/kg in the subsequent hours. | Drug: Voluven (Hydroxyethyl starch 130/0,4)<br>* 7,5 ml/kg in the first hour and then 5 ml/kg<br>* Other names: Hydroxyethyl starch;|
| Placebo Comparator: Sodium Chloride 9 mg/ml<br>Patients undergoing hip replacement surgery will receive either fluid therapy with active comparator (Voluven) or placebo (Sodium Chloride. Patients will receive minimum 7,5 ml/kg in the first hour of the surgery and 5 ml/kg in the subsequent hours. | Drug: Sodium Chloride 9 mg/ml<br>* 7,5 ml/kg in the first hour and then 5 ml/kg<br>* Other names: Isotone saline solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| u-NGAL | The main objective is for the trial (only patients undergoing elective hip replacement surgery) to measure the effect of hydroxyethyl starch on u-NGAL, which is a biomarker of nephrotoxicity | 2-4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| u-Kim1, u-LFABP | Another objective of the trial (only patients undergoing elective hip replacement surgery) to measure the effect of hydroxyethyl starch on u-Kim1 and u-LFABP, which are biomarkers of nephrotoxicity | 2-4 hours | 
| FENa, u-ENaCβ, CH2O, u-AQP2,u-NCC, u-NK2CC | Secondarily to measure the effect of hydroxyethyl starch on the renal tubular transport of sodium and water during elective hip replacement surgery | 2-4 hours | 
| PRC, p-Ang-II, p -Aldo, p-ANP,P-GDP, p-AVP, p-Endot | Secondarily to measure the effect of hydroxyethyl starch on vasoactive hormones during elective hip replacement surgery | 2-4 hours | 
| SBP, DBP, heartrate | Secondarily to measure the effect of hydroxyethyl starch on central hemodynamics during elective hip replacement surgery | 2-4 hours |