Abstract
BackgroundSepsis is the most common trigger for AKI and up to 40% of mild or moderate septic AKI would progress to more severe AKI, which is associated with significantly increased risk for death and later CKD/ESRD. Early identifying high risk patients for AKI progression is a major challenge in patients with septic AKI.MethodsThis is a prospective, multicenter cohort study which enrolled adult patients with sepsis and initially developed stage 1 or 2 AKI in the intensive care unit from January 2014 to March 2018. AKI was diagnosed and staged according to 2012 KDIGO-AKI guidelines. Renal cell arrest biomarkers (urinary TIMP2*IGFBP7, u[TIMP-2]*[IGFBP7]) and renal damage biomarkers (urinary KIM-1[uKIM-1] and urinary IL-18 [uIL-18]) were measured at time of AKI clinical diagnosis, and the performance of biomarkers for predicting septic AKI progression alone or in combination were evaluated. The primary outcome was AKI progression defined as worsening of AKI stage. The secondary outcome was AKI progression with subsequent death during hospitalization.ResultsAmong 433 screened patients, 149 patients with sepsis and stage 1 or 2 AKI were included, in which 63 patients developed progressive AKI and 49 patients subsequently died during hospitalization. u[TIMP-2]*[IGFBP7], uKIM-1 and uIL-18 independently predicted the progression of septic AKI in which u[TIMP-2]*[IGFBP7] showed the greatest AUC (0.745; 95%CI, 0.667-0.823) as compared to uKIM-1 (AUC 0.719; 95%CI 0.638-0.800) and uIL-18 (AUC 0.619; 95%CI 0.525-0.731). Combination of u[TIMP-2]*[IGFBP7] with uKIM-1 improved the performance of predicting septic AKI progression with AUC of 0.752. u[TIMP-2]*[IGFBP7], alone or combined with uKIM-1/uIL-18, improved the risk reclassification over the clinical risk factor model alone both for the primary and secondary outcomes, as evidenced by significant category-free net reclassification index.ConclusionsCombination of renal cell arrest and damage biomarkers enhanced the prediction of AKI progression in patients with sepsis and improved risk reclassification over the clinical risk factors.
Highlights
Sepsis is the most common trigger for Acute kidney injury (AKI) and up to 40% of mild or moderate septic AKI would progress to more severe AKI, which is associated with significantly increased risk for death and later CKD/ESRD
Progression with category-free net reclassification improvement (NRI) of 0.61 and 0.67, respectively (Table S2). In this prospective, multicenter cohort study of adult patients with sepsis, we firstly showed that combining renal cell arrest biomarker and renal injury biomarkers could enhance the ability of biomarkers for predicting the progression of septic AKI. u[tissue inhibitor of metalloproteinases-2 (TIMP-2)]*[IGFBP7], measured at time of AKI diagnosis, predicted both AKI progression and AKI progression with death in the setting of sepsis
Our results showed that combining u[TIMP-2]*[IGFBP7] with urinary KIM-1 (uKIM-1) could further improve the prediction of septic AKI progression compared to single biomarker prediction, which was true for predicting AKI progression with death, suggesting that carefully selecting and combining biomarkers might be a better approach for greater application
Summary
Sepsis is the most common trigger for AKI and up to 40% of mild or moderate septic AKI would progress to more severe AKI, which is associated with significantly increased risk for death and later CKD/ESRD. Previous study showed that up to 40% these mild or moderate AKI would progress to more severe AKI (KDIGO stage 3), of which 30% required dialysis and the risk of death increased by 3-fold, as high as 70% [5]. Early identifying patients at high risk for progressive AKI might help clinicians to enhance individualized monitoring and personalized management in patient with septic AKI, which might prevent or halt the ongoing renal injury and improve the outcome of patients with sepsis
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