Biomarkers for the Early Detection and Prognosis of Acute Kidney Injury

Abstract

AKI is an increasingly common disorder that is strongly linked to short- and long-term morbidity and mortality. Despite a growing heterogeneity in its causes, providing a timely and certain diagnosis of AKI remains challenging. In this review, we summarize the evolution of AKI biomarker studies over the past few years, focusing on two major areas of investigation: the early detection and prognosis of AKI. We highlight some of the lessons learned in conducting AKI biomarker studies, including ongoing attempts to address the limitations of creatinine as a reference standard and the recent shift toward evaluating the prognostic potential of these markers. Lastly, we suggest current gaps in knowledge and barriers that may be hindering their incorporation into care and a full ascertainment of their value.

Have biomarkers failed in acute kidney injury? No

“…Over the past decade, large prospective cohort studies have repeatedly shown that novel biomarkers are superior in performance to serum creatinine (SCr) in the early diagnosis and prognosis of acute kidney injury (AKI) with this data being summarized in recent reviews [1,2]. Several investigations have linked these first-generation serum and urinary biomarkers of AKI [e.g., neutrophil gelatinase-associated lipocalin (NGAL) or tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7)] with adverse patient outcomes even in the absence of a change in SCr concentrations (biomarker-"positive"/creatinine-"negative" status) [3,4].…”

“…It took decades to overcome the barriers and refine the assays before the high sensitivity troponin immunoassays could be optimized for use. The association of first-generation biomarkers with clinically meaningful endpoints such as early AKI, progression of AKI, need for RRT, and long-term mortality is clear [1,2]. As above, a recent consensus statement included biomarkers in the definitions of AKI and given the imperfections of SCr and difficulty in assessing renal reserve there is increasing acceptance of the importance of the biomarker-positive creatinine-negative cohorts [9].…”

Have biomarkers failed in acute kidney injury? We are not sure

“…More than 15 separate biomarkers, plasma and urine, have been identified and investigated to various levels, the majority in the context of AKI complicating critical illness [1]. However, opinion remains divided as to the clinical value of biomarker measurements in the care of patients at risk or with AKI, as reflected in opposing opinion pieces in this issue of Intensive Care Medicine.…”

“…Studies of biomarkers have occurred in several large prospective cohorts with differing clinical settings (post-surgery, post-procedure, sepsis, emergency department) and different timing of biomarker measurements. However, in just about every study, the discrimination for AKI detection is modest with area under the curves (AUCs) typically between 0.7 and 0.8 for most biomarkers [1]. Notably, in the circumstances where biomarkers performed best, such as pediatric cardiac surgery [2] and in animal models [3], the renal insult was precisely timed, the cause of AKI fairly uniform and the clinical population homogenous.…”

“…Conversely, interventional studies of biomarker-targeted intervention are a very promising approach avoiding the limitations of conventional AKI diagnosis, but require careful matching of biomarker, setting and intervention to be successful. 1 Queen Mary University of London Adult Critical Care Unit, Royal London Hospital, Whitechapel Road, London E1 1BB, UK.…”