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Because of its still rising incidence and high mortality rate in intensive care unit (ICU) patients, early recognition of acute kidney injury (AKI) remains a critical issue. Surprisingly, effective biomarkers for early detection and hence appropriate and timely therapy of AKI have not yet entered the clinical arena. We performed a systematic search of the literature published between 1999 and 2011 on potential early biomarkers for acute renal failure/kidney injury in an at-risk adult and pediatric population following the Quorum Guidelines. Based on this review, recommendations for the clinical use of these biomarkers were proposed. In general, kidney biomarkers may aid to direct early aggressive treatment strategies for AKI thereby decreasing the associated high mortality. To date, however, sensitivity and specificity of individual biomarker assays are low and do not sustain their routine clinical use. “Kits” containing a combination of established biomarkers, in conjunction with measured glomerular filtration rate, may enhance diagnostic and prognostic accuracy in the future.