Biomarkers of acute kidney injury

Abstract

Acute kidney injury (AKI) is a common condition with a high risk of death. The standard metrics used to define and monitor the progression of AKI, such as serum creatinine and blood urea nitrogen levels, are insensitive, nonspecific, and change significantly only after significant kidney injury and then with a substantial time delay. This delay in diagnosis not only prevents timely patient management decisions, including administration of putative therapeutic agents, but also significantly affects the preclinical evaluation of toxicity thereby allowing potentially nephrotoxic drug candidates to pass the preclinical safety criteria only to be found to be clinically nephrotoxic with great human costs. Studies to establish effective therapies for AKI will be greatly facilitated by two factors: (a) development of sensitive, specific, and reliable biomarkers for early diagnosis/prognosis of AKI in preclinical and clinical studies, and (b) development and validation of high-throughput innovative technologies that allow rapid multiplexed detection of multiple markers at the bedside.

Figure 1

Schematic representation of (a) pathophysiological and (b) cellular mechanisms of acute kidney injury.

Figure 2

(a) Kidney injury continuum: The process of acute kidney injury can be divided into various reversible stages depending on the severity of insult, starting from increased risk to damage followed by decrease in glomerular filtration rate (GFR) further progressing to kidney failure and death. Diminished renal perfusion may result in decreased GFR in the absence of intrinsic damage, a condition termed prerenal azotemia. (b) Biomarkers of AKI: Traditionally used markers, such as blood urea nitrogen (BUN) and creatinine (CR), are insensitive, nonspecific, and do not adequately differentiate between the different stages of AKI. A delay in diagnosis prevents timely patient management decisions, including administration of putative therapeutic agents. Urinary biomarkers of AKI will facilitate earlier diagnosis and specific preventative and therapeutic strategies, ultimately resulting in fewer complications and improved outcomes.