Subclinical AKI: ready for primetime in clinical practice?

There has been considerable progress over the last decade in the standardization of the acute kidney injury (AKI) definition with the publication of the RIFLE, AKIN, KDIGO and ERBP classification criteria. However, these classification criteria still rely on imperfect parameters such as serum creatinine and urinary output. The use of timed urine collections, kinetic eGFR (estimated glomerular filtration rate), real time measurement of GFR and direct measures of tubular damage can theoretically aid in a more timely diagnosis of AKI and improve patients' outcome. There has been an extensive search for new biomarkers indicative of structural tubular damage but it remains controversial whether these new markers should be included in the current classification criteria. The use of these markers has also led to the creation of a new concept called subclinical AKI, a condition where there is an increase in biomarkers but without clinical AKI, defined as an increase in serum creatinine and/or a decrease in urinary output. In this review we provide a framework on how to critical appraise biomarker research and on how to position the concept of subclinical AKI. The evaluation of biomarker performance and the usefulness of the concept 'subclinical AKI' requires careful consideration of the context these biomarkers are used in (clinical versus research setting) and the goal we want to achieve (risk assessment versus prediction versus early diagnosis versus prognostication). It remains currently unknown whether an increase in biomarkers levels without functional repercussion is clinically relevant and whether including biomarkers in classification criteria will improve patients' outcome.