Validating benefit of biomarker-directed therapy for acute kidney injury: can you have your cake and eat it?

Excerpt

Despite well-defined diagnostic criteria [1] there is currently little evidence that, beyond supportive care, targeted interventions for acute kidney injury (AKI) beneficially affect outcomes after AKI diagnosis. These failures can be explained by a time lag between the development of tubular injury, changes in GFR and the eventual rise in serum creatinine that signifies an AKI diagnosis, and also by the imprecise relationship between alteration in urine output and underlying AKI. As a result, renal pathology may be well established at the time of attempted intervention. In recognition of these limitations, over the last 15 years there has been a focus on the identification and characterization of plasma and urinary biomarkers for early renal injury [2]. However, efforts to validate and clinically apply these biomarkers have been hampered by the inadequate gold standard for current AKI diagnosis. Furthermore, proof of a statistical association with the development of AKI is very far from a demonstration that biomarker measurement will meaningfully alter physician treatment choices or clinical outcomes [3]. Consequently, until now there have been no positive reports of prospective randomized studies for biomarker-driven interventions for AKI, nor have any novel biomarkers been considered ready for incorporation into AKI diagnostic systems [4]. Given these concerns we have previously commented in this journal that, “prospective studies comparing outcomes from biomarker-directed care against conventional clinical and biochemical-directed intervention may be the only way to truly establish the clinical value of novel (AKI) diagnostics” [5] and there is currently significant interest in how to incorporate renal biomarkers into interventional studies (Fig. 1) [6].

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