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Background This substudy of the randomized IDEAL-ICU trial assessed whether the timing of renal replacement therapy (RRT) initiation has a differential effect on 90-day mortality, according to the criteria used to diagnose acute kidney injury (AKI), in patients with early-stage septic shock. Methods Three groups were considered according to the criterion defining AKI: creatinine elevation only (group 1), reduced urinary output only (group 2), creatinine elevation plus reduced urinary output (group 3). Primary outcome was 90-day all-cause death. Secondary endpoints were RRT-free days, RRT dependence and renal function at discharge. We assessed the interaction between RRT strategy (early vs. delayed) and group, and the association between RRT strategy and mortality in each group by logistic regression. Results Of 488 patients enrolled, 205 (42%) patients were in group 1, 174 (35%) in group 2, and 100 (20%) in group 3. The effect of RRT initiation strategy on 90-day mortality across groups showed significant heterogeneity (adjusted interaction p  = 0.021). Mortality was 58% vs. 42% for early vs. late RRT initiation, respectively, in group 1 ( p  = 0.028); 57% vs. 67%, respectively, in group 2 ( p  = 0.18); and 58% vs. 55%, respectively, in group 3 ( p  = 0.79). There was no significant difference in secondary outcomes. Conclusion The timing of RRT initiation has a differential impact on outcome according to AKI diagnostic criteria. In patients with elevated creatinine only, early RRT initiation was associated with significantly increased mortality. In patients with reduced urine output only, late RRT initiation was associated with a nonsignificant, 10% absolute increase in mortality. Key points Question: Can acute kidney injury (AKI) diagnostic criteria modify the impact of the timing of renal replacement therapy (RRT)? Findings: In this post hoc analysis of a randomized clinical trial that included 488 adults, the effect of RRT initiation strategy on 90-day mortality across groups showed significant heterogeneity. Mortality was 58% vs. 42% for early vs late RRT initiation in the creatinine elevation only group, a significant difference. Meaning: The timing of RRT initiation has a differential impact on outcome according to AKI diagnostic criteria.

Background: KDIGO (Kidney Disease: Improving Global Outcomes) defines acute kidney injury (AKI) solely by serum creatinine (SCr) and urine output variation. Severe AKI is a syndrome covering various clinical situations. Objective: To describe severe AKI heterogeneity by department of hospitalization. Design: This is a prospective observational single-center study. Setting: Adult patients hospitalized in a French tertiary hospital from August 2016 to December 2017. Patients: All adults with severe AKI, defined by dialysis for AKI or an increase in SCr above 354 μmol/L. Measurements: Patient characteristics, clinical and laboratory presentation, AKI cause, medical indication for renal replacement therapy (RRT), planned palliative care, and vital status 30 days after severe AKI. Methods: A global description of patient characteristics, care, and prognosis and comparison by department of hospitalization: intensive care unit (ICU), nephrology, and others. Results: The study included 480 patients (73% men, median age: 72 years, range: 64-83), with medical histories including cardiovascular disease, diabetes, cancer, and chronic kidney disease. Principal causes were sepsis (104; 22%), hypovolemia (98; 20%), obstructive AKI (84; 18%), acute tubular necrosis (ATN; 74; 15%), and cardiorenal syndrome (51; 11%). Severe AKI was diagnosed in the ICU for 188 (39%) patients, the nephrology department for 130 (27%), and in other wards for 162 (34%). Patient characteristics differed by department for age, comorbidity, cause, and RRT use and indications. Palliative care was planned for 72 (15%) patients, most frequently in other wards. Limitations: We studied a subgroup of stage 3 KDIGO AKI patients in a single center without cardiac surgery. Conclusion: Patients hospitalized for severe AKI have frequent and various comorbidities, different clinical presentations, care, hospitalization in various departments, and different prognosis. The heterogeneity of this severe AKI implies the need for personalized care, which requires prognostic tools that include information besides SCr and diuresis.

Sepsis is a life-threatening organ dysfunction with high mortality rate. The gut origin hypothesis of multiple organ dysfunction syndrome relates to loss of gut barrier function and the ensuing bacterial translocation. The aim of this study was to describe the evolution of gut microbiota in a cohort of septic shock patients over seven days and the potential link between gut microbiota and bacterial translocation. Sixty consecutive adult patients hospitalized for septic shock in intensive care units (ICU) were prospectively enrolled. Non-inclusion criteria included patients with recent or scheduled digestive surgery, having taken laxatives, pre- or probiotic in the previous seven days, a progressive digestive neoplasia, digestive lymphoma, chronic inflammatory bowel disease, moribund patient, and pregnant and lactating patients. The primary objective was to evaluate the evolution of bacterial diversity and richness of gut microbiota during seven days in septic shock. Epidemiological, clinical and biological data were gathered over seven days. Gut microbiota was analyzed through a metagenomic approach. 100 healthy controls were selected among healthy blood donors for reference basal 16S rDNA values. Significantly lower bacterial diversity and richness was observed in gut microbiota of patients at Day 7 compared with Day 0 (p<0.01). SOFA score at Day 0, Acute Gastrointestinal Injury (AGI) local grade, septic shock origin and bacterial translocation had an impact on alpha diversity. A large increase in Enterococcus genus was observed at Day 7 with a decrease in Enterobacterales, Clostridiales, Bifidobacterium and other butyrate-producing bacteria. This study shows the importance of bacterial translocation during AGI in septic shock patients. This bacterial translocation decreases during hospitalization in ICUs in parallel to the decrease of microbiota diversity. This work highlights the role of gut microbiota and bacterial translocation during septic shock.

A multicenter, randomized, controlled trial compared early with delayed strategies of renal-replacement therapy in patients with early-stage septic shock who had severe acute kidney injury. There was no significant between-group difference in overall mortality at 90 days.