Evaluation of 32 urine biomarkers to predict the progression of acute kidney injury after cardiac surgery

Abstract

Biomarkers for acute kidney injury (AKI) have been used to predict the progression of AKI but a systematic comparison of the prognostic ability of each biomarkers alone or in combination has not been performed. In order to assess this, we measured the concentration of 32 candidate biomarkers in the urine of 95 patients with AKIN stage 1 after cardiac surgery. Urine markers were divided into eight groups based on the putative pathophysiologic mechanism they reflect. We then compared the ability of the markers alone or in combination to predict the primary outcome of worsening AKI or death (23 patients) and the secondary outcome of AKIN stage 3 or death (13 patients). IL-18 was the best predictor of both outcomes (AUC of 0.74 and 0.89). L-FABP (AUC of 0.67 and 0.85), NGAL (AUC of 0.72 and 0.83) and KIM-1 (AUC of 0.73 and 0.81) were also good predictors. Correlation between most of the markers was generally related to their predictive ability but KIM-1 had a relatively weak correlation with other markers. The combination of IL-18 and KIM-1 had a very good predictive value with an AUC of 0.93 to predict AKIN 3 or death. Thus, combination of IL-18 and KIM-1 would result in improved identification of high risk patients for enrollment in clinical trials.

Urinary Biomarkers at the Time of AKI Diagnosis as Predictors of Progression of AKI among Patients with Acute Cardiorenal Syndrome

“…Consistently, our results confirmed the ability of uIL-18 and uNGAL to predict worsening of AKI in acute CRS. However, we did not find benefit to pNGAL, uKIM-1, and UACR measurements after adjusting for variables known to affect AKI progression, although prior reports show these biomarkers may predict worsening of AKI (18,19). Notably, these prior reports were not specific to ADHF.…”

“…Most of these studies are conducted in patients after cardiac surgery (18,19). A recent study tested the ability of 32 biomarkers to predict worsening of renal function in patients with AKIN stage 1 AKI after cardiac surgery (19). They found that uIL-18 was the best predictor of worsening AKI or death.…”

“…However, the identification of biomarkers that predict the outcomes of patients with established AKI has not been fully highlighted. Most of these studies are conducted in patients after cardiac surgery (18,19). A recent study tested the ability of 32 biomarkers to predict worsening of renal function in patients with AKIN stage 1 AKI after cardiac surgery (19).…”

“…Diagnostic mainstays such as the fractional excretion of sodium and urea have been shown to be suboptimal in a variety of clinical settings (13)(14)(15)(16)(17). Assessment of biomarkers for renal tubular injury (e.g., neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1] and IL-18) at the time of creatinine-based diagnosis of AKI offers prognostic information in multiple clinical settings such as cardiac surgery, ICU, transplantation, and cirrhosis (18)(19)(20)(21)(22)(23). However, their utility has not been tested in ADHF.…”

Biomarkers for AKI improve clinical practice: no

“…Consequently, research in the last decade has focussed on the discovery and validation of more specific and sensitive markers of tubular damage/functional impairment. The most advanced biomarkers promise to identify patients at risk of AKI, diagnose AKI earlier than conventional tests and prognosticate risk of progression, including need for (RRT) renal replacement therapy [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. The hope is that, with such an approach and more timely and relevant interventions, the outcome of patients with AKI can be improved.…”