Some biomarkers of acute kidney injury are increased in pre-renal acute injury

Pre-renal acute kidney injury (AKI) is assumed to represent a physiological response to underperfusion. Its diagnosis is retrospective after a transient rise in plasma creatinine, usually associated with evidence of altered tubular transport, particularly that of sodium. In order to test whether pre-renal AKI is reversible because injury is less severe than that of sustained AKI, we measured urinary biomarkers of injury (cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), γ-glutamyl transpeptidase, IL-18, and kidney injury molecule-1 (KIM-1)) at 0, 12, and 24?h following ICU admission. A total of 529 patients were stratified into groups having no AKI, AKI with recovery by 24?h, recovery by 48?h, or the composite of AKI greater than 48?h or dialysis. Pre-renal AKI was identified in 61 patients as acute injury with recovery within 48?h and a fractional sodium excretion <1%. Biomarker concentrations significantly and progressively increased with the duration of AKI. After restricting the AKI recovery within the 48?h cohort to pre-renal AKI, this increase remained significant. The median concentration of KIM-1, cystatin C, and IL-18 were significantly greater in pre-renal AKI compared with no-AKI, while NGAL and γ-glutamyl transpeptidase concentrations were not significant. The median concentration of at least one biomarker was increased in all but three patients with pre-renal AKI. Thus, the reason why some but not all biomarkers were increased requires further study. The results suggest that pre-renal AKI represents a milder form of injury.