Biomarker Predictors of Adverse Acute Kidney Injury Outcomes in Critically Ill Patients: The Dublin Acute Biomarker Group Evaluation Study

Abstract

Background: The Dublin Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective 2-center observational study investigating the utility of urinary biomarker combinations for the diagnostic and prognostic assessment of acute kidney injury (AKI) in a heterogeneous adult intensive care unit (ICU) population. The objective of this study is to evaluate whether serial urinary biomarker measurements, in combination with a simple clinical model, could improve biomarker performance in the diagnostic prediction of severe AKI and clinical outcomes such as death and need for renal replacement therapy (RRT). Methods: Urine was collected daily from patients admitted to the ICU, for a total of 7 post-admission days. Urine biomarker concentrations (neutrophil gelatinase-associated lipocalin [NGAL], α-glutathione S-transferase [GST], π-GST, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], Cystatin C, creatinine, and albumin) were measured. Urine biomarkers were combined with a clinical prediction of AKI model, to determine ability to predict AKI (any stage, within 2 days or 7 days of ICU admission), or a ­30-day composite clinical outcome (RRT – or death). Results: A total of 257 (38%) patients developed AKI within 7 days of ICU admission. Of those who developed AKI, 106 (41%) patients met stage 3 AKI within 7 days of ICU admission and 208 patients of the entire study cohort (31%) met the composite clinical endpoint of in-hospital mortality or RRT within 30 days of ICU admission. The addition of urinary NGAL/albumin to the clinical model modestly improved the prediction of AKI, in particular severe stage 3 AKI (area under the curve [AUC] of 0.9 from 0.87, p = 0.369) and the prediction of 30-day RRT or death (AUC 0.83 from 0.79, p = 0.139). Conclusion: A clinical model incorporating severity of illness, patient demographics, and chronic illness with currently available clinical biomarkers of renal function was strongly predictive of development of AKI and associated clinical outcomes in a heterogeneous adult ICU population. The addition of urinary NGAL/albumin to this simple clinical model improved the prediction of severe AKI, need for RRT and death, but not at a statistically or clinically significant level, when compared to the clinical model alone.

Urine Neutrophil Gelatinase-associated Lipocalin (NGAL) for Prediction of Persistent AKI and Major Adverse Kidney Events

“…There have been few predictive models using urine biomarkers for prediction of AKI and AKI outcomes. Mcmahon et al demonstrated the addition of urinary NGAL/albumin to the clinical model modestly improved the prediction of AKI, in particular severe stage 3 AKI and the prediction of 30-day RRT or death 24 . The TRIBE study showed that postoperative urine IL-18 and plasma NGAL improved AKI prediction over clinical model alone from AUC of 0.69 to 0.76 and 0.75, respectively 21 .…”

Defining Early Recovery of Acute Kidney Injury

“…This phenomenon was highlighted in the 2012 KDIGO AKI guidelines, which first proposed a decrement in serum creatinine of $50% occurring within a week as a retrospective definition of AKI (1). Similarly, in our recent prospective study of a critically ill cohort, we used a threshold of a $33% decrease from the intensive care unit admission (reference) serum creatinine during the first 7 days to identify patients with recovering AKI at admission (10). An additional 177 AKI cases (26% of total cohort, added to 38% who developed AKI by standard KDIGO criteria; with an overall AKI incidence of 65%) were identified using this criterion.…”

Urinary liver-type fatty acid-binding protein variation as a predictive value of short-term mortality in intensive care unit patients

“…The mechanism by which urinary L-FABP affects prognosis is yet to be elucidated but may be related to L-FABP being a marker that reflects systemic organ ischemia. Urinary L-FABP is considered a useful marker for renal ischemia [3][4][5], and in cases where urinary L-FABP is high, ischemia may occur in other organs. Thuijls et al reported a link between increased urinary L-FABP levels and intestinal damage [8].…”

“…We found that urinary L-FABP-positive cases were significantly associated with AKI development when compared to L-FABP-negative cases; however, there was no such association observed with mortality. In contrast, urinary L-FABP was reported to predict AKI as a renal ischemia marker from an early stage [ 3 , 4 ]. Contrary to our previous findings, Doi et al reported an association between urinary L-FABP and 14-day mortality, in addition to the onset of AKI [ 5 ].…”