AKI Therapeutic Window and Markers of Injury

Therapeutic Window in Volume-Responsive and Volume-Unresponsive AKI12

A conceptual model of interrelated factors involved in the development of AKI is shown in the figure. As kidney function worsens and biomarkers of kidney injury (eg, blood urea nitrogen [BUN] and SCr) increase, a therapeutic window gradually closes. The risk of mortality increases as kidney function declines.12

AKI may be volume-responsive or volume-unresponsive. Volume-responsive AKI resolves with fluid therapy and prevention of further kidney injury, which are time-dependent interventions. If intervention is delayed, the therapeutic window narrows and risk of intrinsic kidney injury increases. Once intrinsic kidney injury occurs, AKI may not resolve with fluid therapy alone. With delay in AKI diagnosis and treatment kidney function declines, and the risk of mortality increases.

Traditional markers of kidney injury (such as BUN and SCr) are insensitive, nonspecific, and do not clearly demonstrate injury until after significant kidney damage has occurred.18 Many biomarkers with increased sensitivity are under clinical investigation but not yet available in routine clinical practice. Some of these biomarkers—such as kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, and cystatin C—are used in specific conditions.19,20