#684 Prognostic value of changes in the serum indoxyl sulfate concentration in septic-shock-associated AKI: the Tox-AKI cohort study

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Abstract Background and Aims Indoxyl sulfate (IxS) is a gut-derived toxin that accumulates with kidney function loss and presents endothelial toxicity. Elevated serum concentrations of IxS are associated with adverse outcomes in chronic kidney disease. We sought to determine whether changes over time in the serum IxS concentration predict 90-day mortality in patients with septic-shock-associated acute kidney injury (AKI). Method We performed a prospective study in a 16-bed intensive care unit at a university medical center. We included 114 patients with septic shock and AKI within a median [IQR] time of 6.0 [2.0–12.0] hours after norepinephrine initiation. We measured the serum IxS concentration and six other uremic toxins on inclusion and every 24 hours thereafter until day six (seven time points). The aim of this study was to analyze the relationship between changes in serum IxS concentration over the first six days and mortality within 90 days following inclusion using joint modelling for longitudinal and survival data. Results On inclusion, the median serum IxS concentration was significantly higher in stage 3 AKI (3.03 [1.37–5.74] µg/ml, n = 46) than in stage 2 AKI (1.50 [0.66–2.20] µg/ml, n = 34) or stage 1 AKI (0.80 [0.38–1.79] µg/ml, n = 34) (P < 0.001). In the longitudinal analysis, IxS showed significant variation over time (estimate (standard error) −0.160 (0.026) P < 0.0001) and as a function of the AKI stage on each day (0.292 (0.030) P < 0.0001). Fifty-three patients (46.1%) died within 90 days of inclusion. After adjusting for explanatory variables, changes in serum IxS concentration over time were not associated with 90-day mortality (hazard ratio (HR) [95% confidence interval (CI)]: 0.98 [0.92–1.04]). With the exception of hippuric acid and trimethylamine N-oxide (which accumulated to a moderate extent in patients with stage 3 AKI only), we did not observe any significant accumulations of the other assayed uremic toxins in the study participants. Conclusion The change in serum IxS concentration over time correlated with the severity and trajectory of AKI during septic shock but was not associated with 90-day mortality.

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