Physiological biomarkers of acute kidney injury: a conceptual approach to improving outcomes

Abstract

The past 5-10 years have brought significant advances in the identification and validation of novel biochemical biomarkers in the prevention and treatment of acute kidney injury (AKI). These biochemical biomarkers remain research tools but we anticipate that soon they will be employed in clinical practice. A Consensus Conference held by the Acute Dialysis Quality Initiative (ADQI) recently reviewed the evidence, and identified gaps and a research agenda. Furthermore, at this meeting was the birth of an initiative to comprehensively identify new opportunities to characterize the physiological changes during the course of AKI based upon a conceptual framework for the detection and monitoring of renal ischemia-reperfusion injury. This framework includes a transition from monitoring physiological biomarkers of adequate renal perfusion, to pathophysiologic biomarkers of renal hypoperfusion, and finally biomarkers of kidney cell structural injury/damage. Techniques to measure physiological changes in AKI include several physiological variables that might be used in an interactive way to supplement clinical information and biochemical damage biomarkers in the diagnosis and management of AKI. This review summarizes the spectrum of physiological parameters and potential new physiological methods that enable identification of high-risk patients for AKI, facilitate early diagnosis, and differential diagnosis to guide therapeutic management and prognostication. Finally, we propose a research agenda for the next 5 years to facilitate the development and validation of physiological biomarkers in AKI.

Fig. 1

Physiological phases of AKI following ischemia-reperfusion injury. The conceptual framework of physiological biomarkers is superimposed upon the previously established concept of clinical phases of AKI. This figure illustrates progression from risk to prerenal AKI and represents experimental data from ischemia reperfusion but not necessarily other forms of AKI such as drug-induced direct nephrotoxicity. Thus physiological biomarkers are not only needed in the early phase of AKI but throughout the continuum of AKI. The ability to measure these physiological variables may lead to identification of patients at risk for AKI, early diagnosis of AKI and inform therapeutic decisions. These physiological processes represent an integrative environment for the interaction of inflammatory mediators, imbalance in the homeostasis of oxygen, nitric oxide and oxygen radicals causing microcirculatory dysfunction and impaired tissue oxygenation leading to AKI. Reproduced with permission from ADQI [58].

Fig. 2

Application of physiological biomarkers in the spectrum of AKI. Physiological biomarkers including imaging and other novel markers of kidney function can be used across the quadrants to establish normal or abnormal kidney physiological state. The choice of physiological biomarkers would be based on the contributing factors and correlated with clinical and laboratory findings. The physiological biomarkers would be utilized to determine transitions across these groups with sequential measurements. Which physiological biomarkers are used and the thresholds applied will need to be defined further in prospective studies. Reproduced with permission from ADQI [58].