Abstract
BackgroundRecent 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.MethodsFrom 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.ResultsThe 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).ConclusionsIn 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 registrationClinicalTrials.gov number: NCT02444988. Date registered: May 15, 2015.
Highlights
Recent trials have suggested use of balanced crystalloids may decrease the incidence of major adverse kidney events compared to saline in critically ill adults
Study design and oversight To examine the effects of balanced crystalloids versus saline on early biomarkers of acute tubular injury, we performed a pre-specified ancillary study within a large, pragmatic trial comparing balanced crystalloids to saline among critically ill adults
The Isotonic Solutions and Major Adverse Renal Events Trial (SMART) was a cluster-randomized, cluster-crossover trial comparing balanced crystalloids to saline for intravenous fluid administration among 15,802 critically ill adults admitted to five intensive care units (ICUs) at Vanderbilt University Medical Center between June 1, 2015 and April 30, 2017 [4]
Summary
Recent trials have suggested use of balanced crystalloids may decrease the incidence of major adverse kidney events compared to saline in critically ill adults. Recent data from clinical trials suggest that crystalloid composition may affect patient outcomes [4], including kidney injury, but the mechanistic effects of balanced crystalloids versus saline on the development of acute kidney injury (AKI) remain uncertain. A small randomized trial among patients undergoing major abdominal surgery found lower concentrations of urinary neutrophil gelatinase-associated lipocalin (NGAL), an early biomarker of renal tubular injury, with balanced crystalloids compared to saline [11]. Two recent clinical trials found balanced crystalloid solutions decreased the composite of death, RRT, or persistent renal dysfunction during acute illness [4, 14]. Whether the differences in clinical outcomes between balanced crystalloids and saline in these trials were mediated by kidney injury or by other mechanisms remains unknown
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