Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass

Abstract

Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary a and glutathione S-transferases (a-GST and -GST), urinary L-type fatty acid-binding protein (L-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24 h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. Despite statistical significance in receiver-operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24 h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.

Oliguria and Biomarkers of Acute Kidney Injury: Star Struck Lovers or Strangers in the Night?

“…According to Westhuyzen et al [26,] the normalization of urinary enzymes to urinary creatinine appears to improve the utility of tubular markers. Similar findings were reported by Prowle et al [40] in a cohort of surgical patients for prediction of AKI when combining biomarkers of tubular injury (NGAL, π-GST) and glomerular filtration (cystatin C, hepcidin). Whereas the time-profile of the point estimates for (TIMP-2) × (IGFBP-7) values shifted slightly when normalizing to urine creatinine, no relevant difference for diagnosing early AKI was detected in cardiac surgery patients [35].…”

Kinetic estimated glomerular filtration rate and acute kidney injury in cardiac surgery patients

“…The similar perioperative losses in keGFR suffered by both the AKI stage 1 and AKI-min patients facilitate future study to determine the factors associated with renal recovery before AKI stage 1 develops with its greater increased mortality risk [12]. Recent studies have studied the ability of biomarkers, such as urinary neutrophil gelatinase-associated lipocalin, urinary hepcidin, and serum cystatin C to identify early AKI after cardiopulmonary bypass, but before creatinine AKI stage 1 is reached [26,28,29]. The discrimination of keGFR is equal to these individual biomarkers, and given that there is no extra cost to keGFR and less laboratory delay in measuring creatinine than the other biomarkers, studies need to be conducted to determine if keGFR is superior to these biomarkers.…”

Urinary, Plasma, and Serum Biomarkers’ Utility for Predicting Acute Kidney Injury Associated With Cardiac Surgery in Adults: A Meta-analysis

“…All were prospective observational studies, with the exception of one that used a randomized controlled trial cohort. 49 The included studies examined a total of 13 urinary (neutrophil gelatinase- Table 1. Of these studies, 26 reported diagnostic performance in the early postoperative period, whereas 4 studies reported intraoperative data, defined as the period after induction of anesthesia to closure of the thoracic cavity.…”