John W. Pickering, Zoltan H. Endre

Current consensus definitions of Acute Kidney Injury (AKI) utilise thresholds of change in serum or plasma creatinine and urine output. Biomarkers of renal injury have been validated against these definitions. These biomarkers have also been shown to be independently associated with mortality and need for dialysis. For AKI definitions to include these structural biomarkers, there is a need for an independent outcome against which to judge both markers of functional change and structural markers of injury. We illustrate how sensitivity to need for dialysis and death can be used to link functional and structural (biomarker) based definitions of AKI. We demonstrated the methodology in a representative cohort of critically ill patients, in which an increase of plasma creatinine of >26.4 µmol/L in 48 hours or >50% in 7 days (Functional-AKI) had a sensitivity of 62% for death or dialysis within 30 days. In a development sub-cohort the urinary neutrophil-gelatinase-associated-lipocalin threshold with a 62% sensitivity for death or dialysis was 140 ng/ml (Structural-AKI). Using these thresholds in a validation sub-cohort, the risk of death or dialysis relative to those with no AKI by either definition was, for combined Structural-AKI and Functional-AKI 3.11 (95% Confidence interval: 2.53 to 3.55), for those with Structural-AKI but not Functional-AKI 1.51 (1.26 to 1.62), and for those with Functional-AKI but not Structural-AKI 1.34 (1.16 to 1.42). Linking functional and structural biomarkers via sensitivity for death and dialysis is a viable method by which to define thresholds for novel biomarkers of AKI.