Evaluation of clinically available renal biomarkers in critically ill adults: a prospective multicenter observational study

Abstract

Background: Although serum cystatin C (sCysC), urinary N-acetyl-β-D-glucosaminidase (uNAG), and urinary albumin/creatinine ratio (uACR) are clinically available, their optimal combination for acute kidney injury (AKI) detection and prognosis prediction remains unclear. We aimed to assess the discriminative abilities of these biomarkers and their possible combinations for AKI detection and intensive care unit (ICU) mortality prediction in critically ill adults.

Methods: A multicenter, prospective observational study was conducted in mixed medical-surgical ICUs at three tertiary care hospitals. One thousand eighty-four adult critically ill patients admitted to the ICUs were studied. We assessed the use of individual biomarkers (sCysC, uNAG, and uACR) measured at ICU admission and their combinations with regard to AKI detection and prognosis prediction.

Results: AUC-ROCs for sCysC, uNAG, and uACR were calculated for total AKI (0.738, 0.650, and 0.683, respectively), severe AKI (0.839, 0.706, and 0.771, respectively), and ICU mortality (0.727, 0.793, and 0.777, respectively). The panel of sCysC plus uNAG detected total and severe AKI with significantly higher accuracy than either individual biomarkers or the other two panels (uNAG plus uACR or sCysC plus uACR). For detecting total AKI, severe AKI, and ICU mortality at ICU admission, this panel yielded AUC-ROCs of 0.756, 0.863, and 0.811, respectively; positive predictive values of 0.71, 0.31, and 0.17, respectively; and negative predictive values of 0.81, 0.97, and 0.98, respectively. Moreover, this panel significantly contributed to the accuracy of the clinical models for AKI detection and ICU mortality prediction, as measured by the AUC-ROC, continuous net reclassification index, and incremental discrimination improvement index. The comparable performance of this panel was further confirmed with bootstrap internal validation.

Conclusions: The combination of a functional marker (sCysC) and a tubular damage marker (uNAG) revealed significantly superior discriminative performance for AKI detection and yielded additional prognostic information on ICU mortality.

Keywords: Acute kidney injury; Intensive care unit; N-acetyl-β-D-glucosaminidase; Renal biomarker; Serum cystatin C; Urinary albumin/creatinine ratio.

Fig. 1

Admission concentrations of the three biomarkers, stratified by AKI severity. a sCysC. b uNAG. c uACR. Concentrations of the three biomarkers are shown in each AKI severity category (non-AKI [n = 758], mild AKI [stage 1; n = 224], severe AKI [stage 2 and stage 3; n = 102]). * P < 0.05. AKI Acute kidney injury, Cre Creatinine, sCysC Serum cystatin C, uNAG Urinary N-acetyl-β-d-glucosaminidase, uACR Urinary albumin/creatinine ratio

Fig. 2

ROC analysis of three biomarkers and their combinations for AKI detection. Among 1084 adult critically ill patients, 326 (30.07%) were diagnosed with AKI (a total AKI). Of 326 patients with AKI, 102 patients were diagnosed with severe AKI (b severe AKI). AKI Acute kidney injury, ICU Intensive care unit, sCysC Serum cystatin C, uNAG Urinary N-acetyl-β-d-glucosaminidase, uACR Urinary albumin/creatinine ratio

Fig. 3

ROC analysis of the three biomarkers and their combinations for ICU mortality. Among 1084 adult critically ill patients, 66 patients died in the ICU. ICU Intensive care unit, sCysC Serum cystatin C, uNAG Urinary N-acetyl-β-d-glucosaminidase, uACR Urinary albumin/creatinine ratio