On 2017 Jul 12, Christian J. Wiedermann commented:

After critical reading of the paper, the authors' conclusions suggesting renal safety of hydroxyethyl starch (HES) do not appear warranted. Since BMC Anesthesiology does not offer a correspondence or letters-to-the-editor section, where some of the study's limitations could be discussed, I would like to post a comment here.

Zhang et al. describe a multicenter, double-blind, controlled randomized clinical trial that evaluated the renal safety of HES in patients undergoing hip arthroplasty under spinal anesthesia, apparently showing that there is no increase in renal injury with 6% HES 130/0.4 compared with lactated Ringer’s solution during this type of orthopedic surgery:

• The reported methodology for the study provided no information on the statistical approach, either regarding the sample size calculation or the comparisons between groups for each outcome. Thus, it is impossible to determine whether this study, which involved a relatively small patient population (120 patients randomized), was powered sufficiently to detect statistically significant and clinically important differences between HES and Ringer’s lactate in the primary and secondary outcomes.
• Eligibility criteria meant that the patient population did not include patients with American Society of Anesthesiologists physical status score >III, thus limiting this elderly population to those at a lower risk of developing AKI.
• The primary outcome of the study was the levels of urine and plasma neutrophil gelatinase-associated lipocalin (NGAL) and plasma interleukin 18 (IL-18), which were used as biomarkers for the early detection of AKI. NGAL has been widely investigated as a biomarker for AKI; however, its clinical utility remains unclear because of difficulties in interpreting results due to different settings, sampling time points, measurement methods, and cut-off values [Singer E, 2013]. Although IL-18 holds promise as a biomarker for the prediction of AKI, it has only moderate diagnostic value [Lin X, 2015].
• The follow-up period in the study was only 5 days, and consequently HES-induced AKI may have been missed (the FDA and EMA recommended monitoring of renal function in patients for at least 90 days [Wiedermann CJ, 2017].

Thus, no conclusions regarding the renal safety of HES can be drawn from the study. The assessment of the benefit/risk profile associated with the perioperative administration of HES will require rigorously designed, sufficiently powered randomized controlled clinical trials incorporating a clinically meaningful outcome for the licensed dosage/indication in an appropriate patient population. Most clinical research fails to be useful not because of its findings but because of its design [Ioannidis JP, 2016], which is particularly true for studies with HES [Wiedermann CJ, 2014].

On 2017 Jul 12, Christian J. Wiedermann commented:

After critical reading of the paper, the authors' conclusions suggesting renal safety of hydroxyethyl starch (HES) do not appear warranted. Since BMC Anesthesiology does not offer a correspondence or letters-to-the-editor section, where some of the study's limitations could be discussed, I would like to post a comment here.

Zhang et al. describe a multicenter, double-blind, controlled randomized clinical trial that evaluated the renal safety of HES in patients undergoing hip arthroplasty under spinal anesthesia, apparently showing that there is no increase in renal injury with 6% HES 130/0.4 compared with lactated Ringer’s solution during this type of orthopedic surgery:

• The reported methodology for the study provided no information on the statistical approach, either regarding the sample size calculation or the comparisons between groups for each outcome. Thus, it is impossible to determine whether this study, which involved a relatively small patient population (120 patients randomized), was powered sufficiently to detect statistically significant and clinically important differences between HES and Ringer’s lactate in the primary and secondary outcomes.
• Eligibility criteria meant that the patient population did not include patients with American Society of Anesthesiologists physical status score >III, thus limiting this elderly population to those at a lower risk of developing AKI.
• The primary outcome of the study was the levels of urine and plasma neutrophil gelatinase-associated lipocalin (NGAL) and plasma interleukin 18 (IL-18), which were used as biomarkers for the early detection of AKI. NGAL has been widely investigated as a biomarker for AKI; however, its clinical utility remains unclear because of difficulties in interpreting results due to different settings, sampling time points, measurement methods, and cut-off values [Singer E, 2013]. Although IL-18 holds promise as a biomarker for the prediction of AKI, it has only moderate diagnostic value [Lin X, 2015].
• The follow-up period in the study was only 5 days, and consequently HES-induced AKI may have been missed (the FDA and EMA recommended monitoring of renal function in patients for at least 90 days [Wiedermann CJ, 2017].

Thus, no conclusions regarding the renal safety of HES can be drawn from the study. The assessment of the benefit/risk profile associated with the perioperative administration of HES will require rigorously designed, sufficiently powered randomized controlled clinical trials incorporating a clinically meaningful outcome for the licensed dosage/indication in an appropriate patient population. Most clinical research fails to be useful not because of its findings but because of its design [Ioannidis JP, 2016], which is particularly true for studies with HES [Wiedermann CJ, 2014].