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Current assessments of renal function by serum creatinine or blood urea nitrogen display poor sensitivity and specificity for indicating early changes in kidney function and do not differentiate between causes of acute kidney injury (AKI). The discovery, characterization and validation of novel biomarkers specific for structural kidney damage, such as neutrophil gelatinaseassociated lipocalin, kidney injury molecule-1, interleukin-18 and liver fatty acid binding protein enable a timely diagnosis of AKI through better reflection of real-time damage of AKI, promise discrimination of the underlying aetiology and may enable incremental risk identification for worsening AKI, need of renal replacement and death. However, case-mix, comorbidities, aetiology of the renal insult, timing of measurements and selected thresholds for diagnosis influence the performance of these novel biomarkers. Additional studies are necessary before novel biomarkers can be used in routine clinical practice. To answer the question of how to optimally utilize novel biomarkers (the right test, at the right time, on the right patient, for the right clinical setting of AKI) all promising AKI biomarkers should undergo systematic evaluation in various clinical setting of AKI in order to validate the temporal expression patterns of these biomarkers for early detection of AKI, to determine how to combine multiple biomarkers for earlier diagnosis and to discover how the temporal course relates to onset, severity and outcome of AKI. There is a vital need that large future investigations demonstrate the association between biomarkers and hard clinical outcomes independent of serum creatinine concentrations. It needs to be shown that early renoprotective treatment for AKI based on high biomarker levels actually results in an improved outcome. The aim of this review is to discuss early diagnosis of acute kidney injury in critically ill patients by novel biomarkers. Conclusion Until effective renoprotective therapies are available, there is little benefit from early diagnosis of AKI during critical illness. Introduction Acute kidney injury in the intensive care setting (ICU AKI) is a complex disorder with multiple aetiologies and risk factors, various clinical presentations and unpredictable outcomes. Various combinations of ischemic, septic and nephrotoxic effects are the main causes of hospitalacquired AKI in critically ill patients. Today, ICU AKI is often found in the setting of multiple organ failure and occurs rarely as single organ dysfunction. In general, the incidence of hospital-acquired AKI is increasing as physicians subject an increasingly aged patient population to major surgery, aggressive medical therapeutics and extended radiologic interventions. AKI is widespread and occurs in up to 18% of all hospital admissions with reports of up to 67% in critically ill patients in the ICU. ICU AKI represents a continuum of morbidity that can vary from subclinical injury, in which serum creatinine changes minimally, to severe oligoanuric kidney failure requiring renal replacement therapy (up to 4–6%)1. The diagnosis of AKI has a significant negative impact on the prognosis of critically ill patients and is associated with a poor shortand long-term outcome. Recently, it has been recognized that kidney function does not completely recover in many patients and that AKI represents an antecedent to the development to chronic kidney failure, particularly in patients with preexisting chronic kidney disease2. Even the mildest forms of AKI are independently associated with increased, early as well as late, mortality, and the risk increases in the wake of increasingly severe renal injury1. Current management of ICU AKI is restricted to supportive care. Reports on specific pharmacologic interventions to treat established AKI showed minimal effects, if any. The attributable mortality of hospital-acquired AKI, however, remains distressingly high (up to 70%), despite numerous advances in intensive care medicine and renal replacement therapy1. This review discusses targeted renoprotection used in earlier diagnosis of acute kidney injury in critically ill patients. * Corresponding author Email: h-schiffl@t-online.de 1 Department of Internal Medicine IV, University Hospital Munich, University of Munich, Munich, Germany 2 Medizinische Klinik, SRH Wald-Klinikum Gera, Gera, Germany A na es th es io lo gy , P er io pe ra tiv e & Cr iti ca l C ar e M ed ic in e

Earlier diagnosis of acute kidney injury in critically ill patients by novel biomarkers: Moving from supportive care to targeted renoprotection?