Trajectory pattern of serially measured acute kidney injury biomarkers in critically ill patients: a prospective observational study

Abstract

Background: The clinical value of the trajectory of temporal changes in acute kidney injury (AKI) biomarkers has not been well established among intensive care unit (ICU) patients.

Methods: This is a single-center, prospective observational study, performed at a mixed ICU in a teaching medical institute in Tokyo, Japan. Adult ICU patients with an arterial line and urethral catheter were enrolled from September 2014 to March 2015. Patients who stayed in the ICU for less than 48 h and patients with known end-stage renal disease were excluded from the study. Blood and urine samples were collected for measurement of AKI biomarkers at 0, 12, 24, and 48 h after ICU admission. The primary outcome was major adverse kidney events (MAKE) at discharge, defined as a composite of death, dialysis dependency, and persistent loss of kidney function (≥ 25% decline in eGFR).

Results: The study included 156 patients. Serum creatinine-based estimated glomerular filtration rate (eGFR), plasma neutrophil gelatinase-associated lipocalin (NGAL), and urinary liver-type fatty acid-binding protein (uL-FABP) were serially measured and each variable was classified into three groups based on group-based trajectory modeling analysis. While the trajectory curves moved parallel to each other (i.e., "low," "middle," and "high") for eGFR and plasma NGAL, the uL-FABP curves showed distinct trajectory patterns and moved in different directions ("low and constant," "high and exponential decrease," and "high and exponential increase"). These trajectory patterns were significantly associated with MAKE. MAKE occurred in 16 (18%), 16 (40%), and 9 (100%) patients in the "low and constant," "high and exponential decrease," and "high and exponential increase" groups, respectively, based on uL-FABP levels (p-value < 0.001). The initial value and the 12-h change in uL-FABP were both significantly associated with MAKE, even after adjusting for eGFR [Odds ratio (95% confidence interval): 1.45 (1.17-1.83) and 1.43 (1.12-1.88) for increase of initial value and 12-h change of log-transformed uL-FABP by 1 point, respectively].

Conclusions: Trajectory pattern of serially measured urinary L-FABP was significantly associated with MAKE in ICU patients.

Keywords: Acute kidney injury; Biomarker; Group-based trajectory modeling; Liver-type fatty acid-binding protein; Major adverse kidney event; Neutrophil gelatinase-associated lipocalin; Trajectory.

Fig. 1

Study design and statistical model development. After patient enrollment, two types of analyses were performed, i.e., analysis of the trajectory patterns and multivariate logistic regression model. One patient (outlier) was excluded from the analysis of the trajectory patterns for eGFR, due to extremely high values (295.6, 347.0, 391.9, and 328.1 mL/min/1.73 m² at time 0, 12, 24, and 48 h after ICU admission, respectively). ESRD end-stage renal disease, eGFR estimated glomerular filtration rate, uL-FABP urinary liver-type fatty acid-binding protein, ICU intensive care unit, NGAL neutrophil gelatinase-associated lipocalin

Fig. 2

Renal function and AKI biomarkers at different time points. Patients who developed MAKE tended to have higher sCr, lower eGFR, higher plasma NGAL, and higher uL-FABP, as compared to those without MAKE. eGFR estimated glomerular filtration rate, uL-FABP urinary liver-type fatty acid-binding protein, MAKE major adverse kidney events at discharge, NGAL neutrophil gelatinase-associated lipocalin, sCr serum creatinine

Fig. 3

Trajectory patterns of kidney-related variables. Solid lines indicate the mean predicted trajectories. Dashed lines indicate the 95% confidence intervals. Note that NGAL and uL-FABP were log-transformed prior to the trajectory analysis. The trajectory models for eGFR and log (NGAL) showed almost parallel classes, with differences in magnitude only. In contrast, the model for log (uL-FABP) exhibited differences in both the magnitude and direction of changes. The class names of log (uL-FABP) are as follows. “High and exponential increase (H/eI),” “high and exponential decrease (H/eD),” and “low and constant (L/C).” eGFR estimated glomerular filtration rate, uL-FABP urinary liver-type fatty acid-binding protein, NGAL neutrophil gelatinase-associated lipocalin