Evaluate the Nephrotoxicity by 6% Hydroxyethyl Starch 130/0.4 in Old Patients During Orthopaedic Surgery

Evaluate the Nephrotoxicity by 6% Hydroxyethyl Starch 130/0.4 in Old Patients

Hydroxyethyl starch (HES) is commonly used as plasma expander during surgery but may be nephrotoxic as seen in studies in patients with sepsis. The investigators hypothesized that the possible nephrotoxicity of 6% HES 130/0.4 could be revealed by measurements of urinary and plasma neutrophil gelatinase-associated lipocalin and interleukin-18 (IL-18) in old patients with normal renal function during orthopaedic surgery.

Study Overview

• Status: Completed
• Conditions: Total Fluid Volume Increased
• Intervention / Treatment: Drug: Lactate Ringers; Drug: Hydroxyethyl Starch

Detailed Description

Hydroxyethyl starch (HES) is widely used as volume expander to maintain circulation in patients during surgery, trauma, and in critical disease, where a rapid and sustained volume expansion is the goal. However, acute kidney injury (AKI) is sometimes a complication in these patients and HES might be a contributing factor. Acute kidney injury is often diagnosed using a sudden rise in plasma creatinine (p-crea) or an abrupt decrease in urine output. P-crea depends on sex, nutrition, medication,muscle mass, and age and it increases 24 to 48 h after renal injury, so the diagnosis of AKI is delayed when using p-crea alone as an indicator for renal damage. New technology allows for earlier diagnosis of AKI using measurements of biomarkers in urine. Neutrophil gelatinase-associated lipocalin (NGAL) is a small protein, which is filtered via the glomeruli and reabsorbed in the proximal tubules, and thus low concentrations of NGAL can be measured in the blood and urine. Approximately 6 h after a renal injury, NGAL increases rapidly due to an up-regulated expression and secretion in the epithelial cells of the thick ascending limb of Henle's loop, the distal tubules, and the collecting ducts. Thus, NGAL can be used as a marker of renal damage. However, infections and malignancies can give falsely increased levels.

Interleukin-18 (IL-18) is mainly created from proximal kidney tubules which is a proinflammatory factor that can be detected in earlier urine of AKI animal models. There is significant rise in IL-18 levels in urine of AKI confirmed cases(no chronic kidney disease, no urinary tract infections, no prerenal factors), specificity and susceptibility is 90%. As a result, IL-18 can be selected as a biomarker.

Intravenously administrated HES is excreted in urine but is also partly accumulated in the tissues. Studies in animals and humans showed that HES molecules were accumulated in the proximal tubule cells with subsequent vacuolization and swelling-a condition known as osmotic nephrosis. However, recent studies, primarily conducted in patients with sepsis, found impaired renal function even when using tetrastarch. In contrast, perioperative studies found no evidence of AKI after infusion of HES. The investigators hypothesized that 6% HES 130/0.4 had a nephrotoxic effect, which could be revealed by measurements of urinary and plasma NGAL and IL-18; that 6% HES 130/0.4 influenced kidney function differently than crystalloids(lactated Ringer's solution) due to the different pharmacokinetic properties of colloids compared with that of crystalloids.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 90 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Old patients scheduled to undergo orthopaedic surgery under a intravertebral anesthesia. (American Society of Anesthesiologists physical status I-Ⅲ)

Exclusion Criteria:

• Allergy and contraindication to HES
• Infections and malignancies
• Sepsis
• History of heart failure or New York Heart Association(NYHA)>Ⅲ
• Renal failure or Cr>108μmol/L，BUN>8.3mmol/L
• Undergoing dialytic treatments
• Intracranial hemorrhages
• Taking non-steroidal antiinflammatory agent for a long time
• Inability to understand the Study Information Sheet and provide a written consent to take part in the study

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Lactate Ringers; Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery	Drug: Lactate Ringers; Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery; Other Names: LR
Experimental: Hydroxyethyl Starch; 6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery	Drug: Hydroxyethyl Starch; 6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery; Other Names: HES

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of NGAL in Urine on 5 Time Point	Neutrophil gelatinase-associated lipocalin (NGAL) is a small protein, which is filtered via the glomeruli and reabsorbed in the proximal tubules, and thus low concentrations of NGAL can be measured in the blood and urine.	-1d, 0d, 1d, 3d, 5d after surgery
Concentration of IL-18 in Urine on 5 Time Point	IL-18 is mainly created from proximal kidney tubules which is a proinflammatory factor that can be detected in earlier urine of AKI animal models.	-1d, 0d, 1d, 3d, 5d after surgery
Concentration of IL-18 in Plasma on 5 Time Point		-1d, 0d, 1d, 3d, 5d after surgery
Concentration of NGAL in Plasma on 5 Time Point.	concentration of NGAL in plasma on 5 time point. Biomarkers are measured by ELISA.	-1d, 0d, 1d, 3d, 5d after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of β2 Microglobulin in Urine		-1d, 0d, 1d, 3d, 5d after surgery
Estimated Glomerular Filtration Rate(eGFR) on 5 Time Point	eGFR is calculated by concentration of creatinine and CKD-EPI2009	-1d, 0d, 1d, 3d, 5d after surgery
Ratio of the Urine Trace Albumin and Creatinine(ACR) on 5 Time Point	ACR is calculated by the urine trace albumin divided by the urine creatinine	-1d, 0d, 1d, 3d, 5d after surgery

Collaborators and Investigators

• Sponsor: Yuanyuan Zhang
• Collaborators: Tianjin First Central Hospital; Tianjin Union Medical Center
• Investigators: Principal Investigator: Yu Yonghao, M.D.,Ph.D, Tianjin Medical University General Hospital

Publications and helpful links

General Publications

• Zhang Y, Yu Y, Jia J, Yu W, Xu R, Geng L, Wei Y. Administration of HES in elderly patients undergoing hip arthroplasty under spinal anesthesia is not associated with an increase in renal injury. BMC Anesthesiol. 2017 Feb 21;17(1):29. doi: 10.1186/s12871-017-0320-8.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: February 2, 2015
• First Submitted That Met QC Criteria: February 6, 2015
• First Posted (Estimate): February 12, 2015

Study Record Updates

• Last Update Posted (Estimate): March 24, 2016
• Last Update Submitted That Met QC Criteria: February 23, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: IRB2014-102-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED