Acute Kidney Injury Biomarkers: What Do They Tell Us?

Abstract

The definition of acute kidney injury (AKI) is now well established and encompasses changes in both the urine output and the serum creatinine (SCr) over time. Many studies to date have concentrated solely on the SCr criteria, as this is relatively easy to monitor, given that accurate urine output is rarely measured outside critical care areas. However, many studies have emphasised the inadequacies of SCr in highlighting potential renal injury in a timely fashion. These limitations reflect not only acute changes in creatinine metabolism in the critically ill but also the kinetics of creatinine generation that may hinder early recognition of AKI. In turn, this may prevent judicious intervention promoting the misconception that little can be done for patients with this devastating condition except treating the consequences. Such observations have led to much research focused on identifying early indicators of AKI that may enable early treatment and hopefully lead to improved outcomes. This explains in part the reasoning behind the interest in biomarkers of AKI and which may see them develop a role as part of established clinical tool(s) in both the assessment of severity of AKI and the potential to assess recovery. However, much of the effort behind biomarker research has focused on the ability of such candidate molecules to predict AKI as defined by the imperfect gold standards used currently. It may be that the presence of renal biomarkers associated with renal stress or injury in isolation dictates poor outcomes and as such may provide diagnostic certainty in their own right.

The determinants, biomarkers, and consequences of microvascular injury in kidney transplant recipients

“…Biomarkers of acute kidney injury. Most of the biomarkers of renal damage characterized in the field of AKI and DGF, such as neutrophil gelatinase-associated lipocain (NGAL) and kidney injury molecule-1 (KIM-1), are associated with tubular injury (9,99). Neither KIM-1 nor NGAL have shown any association with ulterior graft function in patients with DGF (85).…”

Dual assessment of kidney perfusion and pH by exploiting a dynamic CEST‐MRI approach in an acute kidney ischemia–reperfusion injury murine model

“…glomerular filtration rate) by assessing ureic nitrogen (BUN) and Serum creatinine (SCr) in the blood. They are quick and cheap analyses conducted on blood samples, but they can detect injuries only when consistent damage or consistent loss of function have occurred in the kidneys, and are not able to distinguish single kidney injuries [6][7][8][9] . This lack of ability to detect early damage, combined with the inability to distinguish which kidney is involved, is a severe limitation in current diagnoses.…”

Assessment of neutrophil gelatinase-associated lipocalin as an early biomarker for canine renal ischemia-reperfusion injury

“…By far, there have been a large number of studies aimed at a variety of potential biomarkers of AKI under different conditions, such as interleukin-18 (IL-18) (8), kidney injury molecule-1 (KIM-1) (9,10), cysteine protease inhibitor (Cystatin C) (11,12), liver type fatty acid binding protein (L-FABP) (13), tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP-7) (13) and neutrophil gelatinase-associated lipocalin (NGAL). NGAL and IL-18 are both secreted molecules, while KIM-1 and L-FABP are localized on cell membrane and in lysosomes of renal tubular cells separately (9,10). Although the four molecules can reflect the status of kidney injury, there are distribution differences among them.…”

“…Although the four molecules can reflect the status of kidney injury, there are distribution differences among them. The detection of IL-18, KIM-1 and L-FABP may be followed by the apoptosis of renal tubular cells, while NGAL can be released soon even if the injury cells are detected (9,10,13). Other molecules like canine serum Cys C, TIMP-2 and IGFBP-7 are also used, for their reporting of GFR or cell cycle arrest in kidney, but the usage for AKI diagnoses are still under discussion (9,13).…”

“…The detection of IL-18, KIM-1 and L-FABP may be followed by the apoptosis of renal tubular cells, while NGAL can be released soon even if the injury cells are detected (9,10,13). Other molecules like canine serum Cys C, TIMP-2 and IGFBP-7 are also used, for their reporting of GFR or cell cycle arrest in kidney, but the usage for AKI diagnoses are still under discussion (9,13). Among the various early AKI diagnosis mentioned above, NGAL has been used as one of the earliest and most sensitive biomarkers for AKI in mice and humans (14,15).…”