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Background: Hydroxyethyl starch (HES) is applied to achieve volume expansion during surgery; however, nephrotoxicity may be induced in patients with sepsis. Simultaneously, neutrophil gelatinase-associated lipocalin (NGAL) and IL-18 have been illustrated as pivotal indicators to diagnose the acute kidney injury (AKI) early. This multi-center, randomized, double-blinded, placebo-controlled study aimed to investigate whether 6% HES 130/0.4 administration caused postoperative AKI, which can be revealed by urinary and plasma NGAL and IL-18 estimations in elderly patients with normal renal function undergoing hip arthroplasty under spinal anesthesia. Methods: 120 ASA I-III, patients aged >65 y undergoing hip arthroplasty under spinal anesthesia randomly received 6% HES 130/0.4 or sodium lactate Ringer's solution 7.5 mL/kg during the first hour of surgery. 118 patients completed the study. Blood pressure, NGAL concentrations, IL18, β2 micro-albumin and albumin in urine and creatinine, NGAL and IL-18 in plasma were repeatedly measured before, during, and after surgery. Results: The groups were balanced in mean arterial pressure, urine and plasma NGAL, plasma IL-18 and creatinine, urine β2 microalbumin and albumin (P > 0.05). Urine IL-18 was dramatically elevated in both groups after surgery (P < 0.05), but did not vary significantly between the groups (P > 0.05). Conclusion: Elderly patients undergoing surgery under spinal anesthesia are a high-risk population in AKI. These patients with normal renal function receiving a spinal anesthesia for a short duration surgery would not develop AKI when 500 mL (small volume) HES is infused. Trial registration: Identifier: NCT02361736. Registration date was 2 February 2015. [ABSTRACT FROM AUTHOR]