Biomarkers for the early detection of acute kidney injury

Abstract

Acute kidney injury (AKI), previously referred to as acute renal failure (ARF), represents a persistent problem in clinical medicine. Despite significant improvements in therapeutics, the mortality and morbidity associated with AKI remain high. A major reason for this is the lack of early markers for AKI, akin to troponins in acute myocardial disease, and hence an unacceptable delay in initiating therapy. Fortunately, the application of innovative technologies such as functional genomics and proteomics to human and animal models of AKI has uncovered several novel genes and gene products that are emerging as biomarkers. The most promising of these are chronicled in this article. These include a plasma panel [neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C] and a urine panel [NGAL, interleukin 18 (IL-18), and kidney injury molecule 1 (KIM)-1]. As they represent sequentially expressed biomarkers, it is likely that the AKI panels will be useful for timing the initial insult and assessing the duration of AKI. Based on the differential expression of the biomarkers, it is also likely that the AKI panels will distinguish between the various types and etiologies of AKI. It will be important in future studies to validate the sensitivity and specificity of these biomarker panels in clinical samples from large cohorts and from multiple clinical situations.

Fig. 1

Three hypothetical receiver-operating characteristic (ROC) curves are shown. The blue (straight) line represents a biomarker with an area under the curve (AUC) of 0.5, which indicates a result that is no better than expected by random chance. The red (middle) curve yields an AUC of about 0.75, which is generally considered a good biomarker. The green (top) curve gives an AUC of approximately 0.9, which would represent an excellent biomarker