Biomarkers of AKI

Abstract

AKI is a common clinical condition associated with a number of adverse outcomes. More timely diagnosis would allow for earlier intervention and could improve patient outcomes. The goal of early identification of AKI has been the primary impetus for AKI biomarker research, and has led to the discovery of numerous novel biomarkers. However, in addition to facilitating more timely intervention, AKI biomarkers can provide valuable insight into the molecular mechanisms of this complex and heterogeneous disease. Furthermore, AKI biomarkers could also function as molecular phenotyping tools that could be used to direct clinical intervention. This review highlights the major studies that have characterized the diagnostic and prognostic predictive power of these biomarkers. The mechanistic relevance of neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, IL-18, livertype fatty acid-binding protein, angiotensinogen, tissue inhibitor of metalloproteinase-2, and IGF-binding protein 7 to the pathogenesis and pathobiology of AKI is discussed, putting these biomarkers in the context of the progressive phases of AKI. A biomarker-integrated model of AKI is proposed, which summarizes the current state of knowledge regarding the roles of these biomarkers and the molecular and cellular biology of AKI.

Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

“…4,24,25,26 Similar efforts are underway in veterinary medicine and show great promise. [28][29][30][31][32][33][34][35][36] (See also, Yerramilli in this issue) An AKI biomarker should be detectable in urine and/or plasma such that it can be assessed routinely and serve as an indicator of kidney function or dysfunction or response to injury.…”

“…Unfortunately, static kidney function tests only detect the impact of these active processes after substantial functional or structural damage has occurred. 4,24 A sensitive and specific predictor that discriminates whether a patient is likely to progress or remain stable with CKD would provide tremendous diagnostic and therapeutic advantage. 4,17,23 For patients with identified progressive CKD, this could provide earlier opportunity to seek subclinical conditions which might be injuring the kidneys and institute more timely monitoring of the disease.…”

“…4,24,25,26 However, this restricted focus to AKI constrains their broader and potentially important application to CKD. Kidney-specific biomarkers that localize to functional renal tubular epithelia (or other kidney-specific loci) and respond to diverse stresses or disruption of normal cellular function have potential to signal the early, specific, and sensitive existence of kidney injury and are perhaps better termed "active kidney injury" biomarkers.…”

“…Despite the interest and efforts to validate KIM-1 as an AKI biomarker in human patients, 7,18,23,24,26,27 The attraction of these novel biomarkers is their exclusive origins to renal tubular epithelia, integral association with cellular activities coupled to stress or damage, and their highly specific analytical evaluation. As such, these markers offer the potential sensitivity and specificity to forecast active and sustained disruption of normal cellular processes as harbingers of subsequent loss of steady-state kidney functions or residual renal mass.…”

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

“…However, to discount the value of biomarkers in the care of patients with AKI would be a mistake. For example, the positive predictive values for identification of AKI are poor (10-30%), but, importantly, negative predictive values are good (86-97%) [6]. Thus, clinical value may lie in directing of low-risk patients away from expensive interventions (such as ICU care), much in the way that d-dimer, troponin and BNP are best used to rule out venous thromboembolism, myocardial infarction and heart failure, respectively.…”