Acute kidney injury (AKI), previously referred to as acute renal failure (ARF), represents a significant and devastating problem in clinical medicine [
1‐
3]. The incidence of AKI varies from 5% of hospitalized patients to 30–50% of patients in intensive care units, and there is now substantial evidence that the incidence is rising at an alarming rate [
4]. Despite significant improvements in therapeutics, the mortality and morbidity associated with AKI remain high. Outstanding advances in basic research have illuminated the pathogenesis of AKI and have paved the way for successful therapeutic approaches in animal models [
2]. However, translational research efforts in humans have yielded disappointing results. 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 [
5,
6]. In current clinical practice, AKI is typically diagnosed by measuring serum creatinine. Unfortunately, creatinine is an unreliable indicator during acute changes in kidney function [
7]. First, serum creatinine levels can vary widely with age, gender, lean muscle mass, muscle metabolism, and hydration status. Second, serum creatinine concentrations may not change until about 50% of kidney function has already been lost. Third, at lower rates of glomerular filtration, the amount of tubular secretion of creatinine results in overestimation of renal function. Finally, during acute changes in glomerular filtration, serum creatinine does not accurately depict kidney function until steady-state equilibrium has been reached, which may require several days. However, animal studies have shown that whereas AKI can be prevented and/or treated by several maneuvers, these must be instituted very early after the insult, well before the rise in serum creatinine [
2,
5]. The lack of early biomarkers of AKI in humans has negatively impacted on a number of landmark clinical trials investigating highly promising therapies for AKI in adults [
8,
9]. In addition, pediatric continuous renal replacement therapy (CRRT) studies have shown an association between increasing degrees of fluid overload at the time of CRRT initiation and mortality [
10]. Early predictive AKI biomarkers could identify patients who may benefit from early initiation of CRRT.