Date Published: September 13, 2016
Publisher: Public Library of Science
Author(s): Nicholas M. Selby, Richard J. Fluck, Nitin V. Kolhe, Maarten W. Taal
Abstract: Nicholas Selby and colleagues describe how the definition of acute kidney injury brings opportunities and challenges in identifying patients at higher risk of adverse outcomes.
Partial Text: Acute kidney injury (AKI), previously termed acute renal failure, has been the focus of increasing attention in the medical and popular press because of its high incidence and strong association with poor patient outcomes. Alarming figures include an incidence of between 5%–22% of hospital admissions and mortality rates that exceed 50% in those most severely affected [1–4]. The impact of AKI in low- and middle-income countries (LMICs) is equally stark: estimates of the global burden of AKI suggest that over 13 million people are affected annually and that AKI contributes to 1.7 million deaths per year . There is also growing appreciation that renal function does not always recover following AKI and that AKI and chronic kidney disease (CKD) have a bidirectional relationship, with each increasing the risk of the other [6,7]. Such long-term health consequences coupled with prolonged hospital stays and considerable health care costs emphasise the huge societal impact of AKI [8,9]. These statistics have led to a number of calls to increase awareness of AKI and allocate more resources towards its prevention and treatment, including the International Society of Nephrology’s 0by25 campaign that aims to eliminate all preventable deaths related to AKI by 2025 [10,11].
In part, increased awareness has sprung from the widespread adoption of international criteria for the definition of AKI that are based on changes in serum creatinine concentration and degree of oliguria (Table 1) [12–14]. These criteria include small changes in serum creatinine alongside larger increments and receipt of renal replacement therapy (RRT). AKI therefore represents a wide spectrum of patients in comparison to historical concepts of acute renal failure. There is no doubt that this harmonisation in AKI definition has been a major step forward, replacing more than 35 previously used definitions in the medical literature  and focussing attention on opportunities of prevention and recognition that arise earlier in the natural history of AKI. A standardised definition is essential for robust epidemiological research to define the magnitude of the problem posed by AKI; a clear association between AKI defined in this way and patient outcomes has been consistently shown across a large number of studies [3,16]. The magnitude of this association is strong (e.g., odds ratios for mortality in the range of 5–10, ), is proportional to the severity of AKI, and remains remarkably consistent across every clinical condition and environment in which it has been studied. Similar high mortality and associations of AKI severity with outcomes are also seen in data from LMICs, despite the relative paucity of studies and the many differences in AKI epidemiology in these settings . These findings have been extremely important in highlighting the challenges posed by AKI much more widely, as is necessary with the majority of AKI care delivered by non-nephrologists . AKI has now become a term that is widely understood in clinical discussions, and the criteria provide a structure for education and guidelines, describing the severity of AKI as well as just its presence. Whilst a standardised definition brings advantages, it also brings challenges when applied to the syndrome of AKI to clinical practice. Although some may take these challenges as reason not to use current AKI classification outside of epidemiological research, we would argue that such an approach would restrict the benefits that a standardised definition of AKI brings. Here, we discuss the practical considerations that are essential to consider when doing so.
At present, we believe the advantages of using the current diagnostic criteria for AKI outweigh perceived disadvantages. However, serum creatinine concentration has a number of limitations as a biomarker of AKI, not least that it is affected by a number of factors other than renal function, the delay before it rises after renal injury, and that as a functional marker it does not provide information about the nature or aetiology of renal damage. These obvious deficiencies have driven extensive research activity to identify novel biomarkers for AKI, although none have yet found a place in clinical practice. There is increasing realisation that a “single-shot” diagnostic biomarker will not be identified, in part reflecting the heterogeneous nature of AKI. Future directions may include: better clinical targeting of biomarkers to phenotypes and/or aetiologies of AKI; the combination of functional and damage biomarkers; or a two-step process, the first highly sensitive but relatively nonspecific, followed by a second, more specific test to rule in the diagnosis [55,56]. Future advances in other diagnostic modalities such as imaging may also support biomarker development.
AKI is a major challenge to health care providers and clinicians. Current diagnostic criteria bring opportunities to identify patients at higher risk of adverse outcomes as well as providing a standardised and evidence-based approach to AKI recognition but require clinical interpretation for individual patient management. Whilst approaches to AKI are hugely different between developed and developing countries, the principles of AKI detection underpin efforts to improve delivery of AKI care as well methods to measure its impact and outcomes.