The intensive care medicine agenda on acute kidney injury

Abstract

Acute kidney injury (AKI) is a common complication in the critically ill. Current standard of care mainly relies on identification of patients at risk, haemodynamic optimization, avoidance of nephrotoxicity and the use of renal replacement therapy (RRT) in established AKI. The detection of early biomarkers of renal tissue damage is a recent development that allows amending the late and insensitive diagnosis with current AKI criteria. Increasing evidence suggests that the consequences of an episode of AKI extend long beyond the acute hospitalization. Citrate has been established as the anticoagulant of choice for continuous RRT. Conflicting results have been published on the optimal timing of RRT and on the renoprotective effect of remote ischaemic preconditioning. Recent research has contradicted that acute tubular necrosis is the common pathology in AKI, that septic AKI is due to global kidney hypoperfusion, that aggressive fluid therapy benefits the kidney, that vasopressor therapy harms the kidney and that high doses of RRT improve outcome. Remaining uncertainties include the impact of aetiology and clinical context on pathophysiology, therapy and prognosis, the clinical benefit of biomarker-driven interventions, the optimal mode of RRT to improve short- and long-term patient and kidney outcomes, the contribution of AKI to failure of other organs and the optimal approach for assessing and promoting renal recovery. Based on the established gaps in current knowledge the trials that must have priority in the coming 10 years are proposed together with the definition of appropriate clinical endpoints.

Keywords: Acute kidney injury; Biomarkers; Fluid therapy; Renal replacement therapy; Research agenda; Trial endpoints.

Fig. 1

Kidney Disease Improving Global Outcomes (KDIGO) classification. Classification of AKI according to KDIGO criteria, defining three grades of severity of AKI on the basis of either the creatinine or urine output criteria

Fig. 2

Current standard of care. This figure illustrates the absence of injury and functional biomarkers (other than creatinine) and clinical follow-up in current practice. Different tools that are available for prevention, early detection, treatment and aftercare are depicted

Fig. 3

Current practice in RRT for AKI. The current standard of timing, vascular access, modality, dose, anticoagulation and weaning from renal replacement therapy. RCT randomised controlled trial, US ultrasound, CRRT continuous renal replacement therapy, IHD intermittent haemodialysis

Fig. 4

Research items to address. The use of potential diagnostic biomarkers could risk stratify those at highest risk of imminent kidney injury. These highest risk individuals could then be enrolled in RCTs evaluating novel therapeutics or processes of care. Also biomarkers could be used to guide the start and discontinuation of RRT. Clinical effects of prevention and treatment bundles as well as e-alert systems should be established. Protein loading to determine renal reserve may aid risk stratification and may also exert therapeutic effects by GFR augmentation. Effects of fluid types and fluid removal strategies on renal endpoints need to be determined. Clearly well-defined clinically relevant endpoints should be integrated. Naturally, as more relevant pathways in the development of AKI will be discovered, new pharmacological interventions that influence these pathways will need to be investigated. Finally, more attention should be paid to long-term follow-up, both for renal as well as other organ endpoints