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

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.

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.

Eligibility Criteria:
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