Biomarker-Guided Risk Assessment for Acute Kidney Injury: Time for Clinical Implementation?

Abstract

Acute kidney injury (AKI) is a common and serious complication in hospitalized patients, which continues to pose a clinical challenge for treating physicians. The most recent Kidney Disease Improving Global Outcomes practice guidelines for AKI have restated the importance of earliest possible detection of AKI and adjusting treatment accordingly. Since the emergence of initial studies examining the use of neutrophil gelatinase-associated lipocalin (NGAL) and cycle arrest biomarkers, tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein (IGFBP7), for early diagnosis of AKI, a vast number of studies have investigated the accuracy and additional clinical benefits of these biomarkers. As proposed by the Acute Dialysis Quality Initiative, new AKI diagnostic criteria should equally utilize glomerular function and tubular injury markers for AKI diagnosis. In addition to refining our capabilities in kidney risk prediction with kidney injury biomarkers, structural disorder phenotypes referred to as “preclinical-” and “subclinical AKI” have been described and are increasingly recognized. Additionally, positive biomarker test findings were found to provide prognostic information regardless of an acute decline in renal function (positive serum creatinine criteria). We summarize and discuss the recent findings focusing on two of the most promising and clinically available kidney injury biomarkers, NGAL and cell cycle arrest markers, in the context of AKI phenotypes. Finally, we draw conclusions regarding the clinical implications for kidney risk prediction.

Meta‐analysis of diagnostic accuracy studies with multiple thresholds: Comparison of different approaches

“…We note that our case study data were somewhat artificial, with the same number of thresholds and same requirement for each threshold (that gave 95% sensitivity, 95% specificity, and maximized the Youden index, respectively) in all primary studies. This specific setting resulted from the original study's aim to identify urinary and plasma NGAL cut‐off concentrations with high sensitivity or high specificity to complement the identification of patients at high kidney risk in clinical research and practice (Albert et al., 2020b, 2021).…”

Predictive Value of Plasma NGAL:Hepcidin-25 for Major Adverse Kidney Events After Cardiac Surgery with Cardiopulmonary Bypass: A Pilot Study

“…Progress has been made in the development of new biomarkers to diagnose and manage AKIs that go beyond the current AKI definition/staging criteria [ 36 ]. Importantly, biomarker-based improved risk assessment after cardiac surgery may guide timely initiation of effective nephroprotective measures addressing hemodynamic and medication adjustments after cardiac surgery [ 37 - 40 ].…”

Serum 5-Hydroxyindoleacetic Acid and Ratio of 5-Hydroxyindoleacetic Acid to Serotonin as Metabolomics Indicators for Acute Oxidative Stress and Inflammation in Vancomycin-Associated Acute Kidney Injury

“…An increase in serum creatinine concentration (SCr) and a reduction in urine output are the current diagnostic markers for VAKI [5,6,10]; however, these traditional markers of kidney function might not be sensitive to kidney damage, and their changes lag several days behind actual changes in glomerular filtration rate (GFR) [11]. Recent studies have shown that novel biomarkers of kidney damage, including kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver-type fatty acid-binding protein, and interleukin-18, increase before SCr [12][13][14][15][16]. However, it is unclear whether these biomarkers could reveal the different AKI-inducing mechanisms and conditions, such as toxicity, nephron obstruction, ischemia, and inflammation [10,11].…”