Sean M Bagshaw, Christoph Langenberg, Michael Haase, Li Wan, Clive N May, Rinaldo Bellomo
OBJECTIVE: To appraise the literature on the value of urinary biomarkers in septic acute kidney injury (AKI).
DESIGN: Systematic review.
SETTING: Academic medical centre.
PATIENTS AND PARTICIPANTS: Human studies of urinary biomarkers.
INTERVENTIONS: None.
MEASUREMENTS AND RESULTS: Fourteen articles fulfilled inclusion criteria. Most studies were small, single-centre, and included mixed medical/surgical adult populations. Few focused solely on septic AKI and all had notable limitations. Retrieved articles included data on low-molecular-weight proteins (beta2-microglobulin, alpha1-microglobulin, adenosine deaminase binding protein, retinol binding protein, cystatin C, renal tubular epithelial antigen-1), enzymes (N-acetyl-beta-glucosaminidase, alanine-aminopeptidase, alkaline phosphatase; lactate dehydrogenase, alpha/pi-glutathione-S-transferase, gamma-glutamyl transpeptidase), cytokines [platelet activating factor (PAF), interleukin-18 (IL-18)] and other biomarkers [kidney injury molecule-1, Na/H exchanger isoform-3 (NHE3)]. Increased PAF, IL-18, and NHE3 were detected early in septic AKI and preceded overt kidney failure. Several additional biomarkers were evident early in AKI; however, their diagnostic value in sepsis remains unknown. In one study, IL-18 excretion was higher in septic than in non-septic AKI. IL-18 also predicted deterioration in kidney function, with increased values preceding clinically significant kidney failure by 24-48 h. Detection of cystatin C, alpha1-microglobulin, and IL-18 predicted need for renal replacement therapy (RRT).
CONCLUSIONS: Few clinical studies of urinary biomarkers in AKI have included septic patients. However, there is promising evidence that selected biomarkers may aid in the early detection of AKI in sepsis and may have value for predicting subsequent deterioration in kidney function. Additional prospective studies are needed to accurately describe their diagnostic and prognostic value in septic AKI.
