Effect of balanced crystalloids versus saline on urinary biomarkers of acute kidney injury in critically ill adults

Funke, Blake E.; Jackson, Karen E.; Self, Wesley H.; Collins, Sean P.; Saunders, Christina T.; Wang, Li; Blume, Jeffrey D.; Wickersham, Nancy; Brown, Ryan M.; Casey, Jonathan D.; Bernard, Gordon R.; Rice, Todd W.; Siew, Edward D.; Semler, Matthew W.

BACKGROUND: Recent trials have suggested use of balanced crystalloids may decrease the incidence of major adverse kidney events compared to saline in critically ill adults. The effect of crystalloid composition on biomarkers of early acute kidney injury remains unknown. METHODS: From February 15 to July 15, 2016, we conducted an ancillary study to the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) comparing the effect of balanced crystalloids versus saline on urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) among 261 consecutively-enrolled critically ill adults admitted from the emergency department to the medical ICU. After informed consent, we collected urine 36 ± 12 h after hospital admission and measured NGAL and KIM-1 levels using commercially available ELISAs. Levels of NGAL and KIM-1 at 36 ± 12 h were compared between patients assigned to balanced crystalloids versus saline using a Mann-Whitney U test. RESULTS: The 131 patients (50.2%) assigned to the balanced crystalloid group and the 130 patients (49.8%) assigned to the saline group were similar at baseline. Urinary NGAL levels were significantly lower in the balanced crystalloid group (median, 39.4 ng/mg [IQR 9.9 to 133.2]) compared with the saline group (median, 64.4 ng/mg [IQR 27.6 to 339.9]) (P < 0.001). Urinary KIM-1 levels did not significantly differ between the balanced crystalloid group (median, 2.7 ng/mg [IQR 1.5 to 4.9]) and the saline group (median, 2.4 ng/mg [IQR 1.3 to 5.0]) (P = 0.36). CONCLUSIONS: In this ancillary analysis of a clinical trial comparing balanced crystalloids to saline among critically ill adults, balanced crystalloids were associated with lower urinary concentrations of NGAL and similar urinary concentrations of KIM-1, compared with saline. These results suggest only a modest reduction in early biomarkers of acute kidney injury with use of balanced crystalloids compared with saline. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02444988. Date registered: May 15, 2015. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-021-02236-x.