Acute Kidney Injury Biomarkers: Are We Ready for the Biomarker Curve?

Acute kidney injury (AKI) is common in critically ill patients and carries severe complications and a high risk of mortality [1]. Consequently, all preventive and protective strategies should be implemented to mitigate the effects of the syndrome. Early recognition of patients at risk due to identifiable exposures or increased susceptibility is a cornerstone of AKI management. Several lines of evidence suggest that markers of acute tubular stress/damage such as TIMP-2 and IGFBP7 (cell cycle arrest biomarkers identified as Nephrocheck [NC]) are useful in the risk assessment for AKI [2, 3]. NC has a very high predictive ability to identify patients likely to develop stage 2/3 AKI within 12 h [4]. In a recent Acute Disease Quality Initiative meeting, a consensus was reached on the possibility to include biomarker results in the definition/classification of AKI utilizing both functional and damage criteria for the diagnosis [5]. Today diagnosis of the syndrome still relies on creatinine and urine output but they only meet the criteria for AKI once kidney dysfunction becomes manifest. There is evidence however that NC and other biomarkers may help to identify patients with tubular damage that may or may not evolve into a clinically manifest syndrome [6, 7]. Furthermore, biomarkers can help to identify patients with worse long-term outcomes [8, 9]. In spite of an important body of literature, there is still a remarkable resistance to the adoption of AKI biomarkers in clinical routine [10]. Skeptical and nihilistic physicians continue to ask for more evidence while enthusiastic groups that would love to adopt biomarkers are frustrated by repeated denials justified by the cost of these diagnostic tools [2, 11]. The Sapphire investigators and others demonstrated that NC predicts AKI stage 2–3 within 12 h before serum creatinine rise [2, 12]. Other studies suggest that new biomarkers significantly add diagnostic and prognostic certainty and enable improved AKI risk assessment in high-risk patients [13]. Although they do not uncover the predominant type of injury (ischemic, toxic, inflammatory) or the specific site of damage (vascular, proximal/distal tubules, etc.), their use appears today definitely justified [2, 14]. The nature of critical illness is however such that patients in the intensive-care unit (ICU) are subject to a subsequent series of insults and their risk to develop AKI may be modified within hours by new exposures. Multiple insults may derive from nephrotoxic drugs, sepsis Received: September 16, 2019 Accepted: September 16, 2019 Published online: October 16, 2019