Kidney360 · 2026
Uremic Toxin Trajectories in Septic Shock-Associated Acute Kidney Injury and Patient Outcomes: The Tox-AKI Study.
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Titeca-Beauport Dimitri, Bodeau Sandra, Brault Clément, Diouf Momar, Mernissi Touria, André Camille, Varennes Olivier, Durand-Maugard Charlotte, Lambour Alexis, Zerbib Yoann, Kontar Loay, Slama Michel, Bennis Youssef, Choukroun Gabriel, Maizel Julien
Аннотация
BACKGROUND: Emerging evidence suggests that uremic toxins (UTs) may exacerbate organ dysfunction in septic-shock-associated AKI. However, the dynamic changes in serum concentrations of these solutes and their specific prognostic implications remain largely unexplored.
METHODS: This prospective study enrolled 114 patients with septic shock and AKI, alongside 15 non-AKI septic shock controls. We measured serum levels of seven UTs (indoxyl sulfate, indole-3-acetic acid, para-cresyl sulfate, para-cresyl glucuronide, hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), and trimethylamine N-oxide ) daily from Day 0 to Day 6. We analysed toxin kinetics and their relationship with 28-day mortality and the time to successful liberation from vasopressor and invasive mechanical ventilation, using joint modelling for longitudinal and survival data.
RESULTS: Upon inclusion, 30% of patients had Stage 1, 30% Stage 2, and 40% Stage 3 AKI. Except for CMPF, all toxins accumulated significantly compared to controls and remained significantly higher in severe AKI throughout the observation period (p<0.001). Indoxyl sulfate showed the strongest longitudinal correlations with serum creatinine (r=0.67, p<0.001). Daily kidney replacement therapy (KRT) status was associated with lower levels of most UTs, with the notable exceptions of indoxyl sulfate (unaffected) and hippuric acid (positively associated). Forty-four patients (39%) died within 28 days. After adjusting for baseline SAPS II and nonrenal SOFA scores, UT trajectories were not significantly associated with 28-day mortality or the time to successful liberation from organ support.
CONCLUSIONS: Changes in serum UT concentrations correlated with the severity and trajectory of AKI during septic shock, and exhibited variable clearance during KRT, but were not independently associated with 28-day mortality or organ support dependence.
METHODS: This prospective study enrolled 114 patients with septic shock and AKI, alongside 15 non-AKI septic shock controls. We measured serum levels of seven UTs (indoxyl sulfate, indole-3-acetic acid, para-cresyl sulfate, para-cresyl glucuronide, hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), and trimethylamine N-oxide ) daily from Day 0 to Day 6. We analysed toxin kinetics and their relationship with 28-day mortality and the time to successful liberation from vasopressor and invasive mechanical ventilation, using joint modelling for longitudinal and survival data.
RESULTS: Upon inclusion, 30% of patients had Stage 1, 30% Stage 2, and 40% Stage 3 AKI. Except for CMPF, all toxins accumulated significantly compared to controls and remained significantly higher in severe AKI throughout the observation period (p<0.001). Indoxyl sulfate showed the strongest longitudinal correlations with serum creatinine (r=0.67, p<0.001). Daily kidney replacement therapy (KRT) status was associated with lower levels of most UTs, with the notable exceptions of indoxyl sulfate (unaffected) and hippuric acid (positively associated). Forty-four patients (39%) died within 28 days. After adjusting for baseline SAPS II and nonrenal SOFA scores, UT trajectories were not significantly associated with 28-day mortality or the time to successful liberation from organ support.
CONCLUSIONS: Changes in serum UT concentrations correlated with the severity and trajectory of AKI during septic shock, and exhibited variable clearance during KRT, but were not independently associated with 28-day mortality or organ support dependence.