Bertrand Pons

BACKGROUND: The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of debate. METHODS: In this multicenter randomized trial, we assigned patients with severe acute kidney injury (Kidney Disease: Improving Global Outcomes [KDIGO] classification, stage 3 [stages range from 1 to 3, with higher stages indicating more severe kidney injury]) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy. With the early strategy, renal-replacement therapy was started immediately after randomization. With the delayed strategy, renal-replacement therapy was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter, or oliguria for more than 72 hours after randomization. The primary outcome was overall survival at day 60. RESULTS: A total of 620 patients underwent randomization. The Kaplan-Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies; 150 deaths occurred among 311 patients in the early-strategy group (48.5%; 95% confidence interval [CI], 42.6 to 53.8), and 153 deaths occurred among 308 patients in the delayed-strategy group (49.7%, 95% CI, 43.8 to 55.0; P=0.79). A total of 151 patients (49%) in the delayed-strategy group did not receive renal-replacement therapy. The rate of catheter-related bloodstream infections was higher in the early-strategy group than in the delayed-strategy group (10% vs. 5%, P=0.03). Diuresis, a marker of improved kidney function, occurred earlier in the delayed-strategy group (P<0.001). CONCLUSIONS: In a trial involving critically ill patients with severe acute kidney injury, we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients. (Funded by the French Ministry of Health; ClinicalTrials.gov number, NCT01932190.).

BACKGROUND: Intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) are the two main RRT modalities in patients with severe acute kidney injury (AKI). Meta-analyses conducted more than 10 years ago did not show survival difference between these two modalities. As the quality of RRT delivery has improved since then, we aimed to reassess whether the choice of IHD or CRRT as first modality affects survival of patients with severe AKI. METHODS: This is a secondary analysis of two multicenter randomized controlled trials (AKIKI and IDEAL-ICU) that compared an early RRT initiation strategy with a delayed one. We included patients allocated to the early strategy in order to emulate a trial where patients would have been randomized to receive either IHD or CRRT within twelve hours after the documentation of severe AKI. We determined each patient's modality group as the first RRT modality they received. The primary outcome was 60-day overall survival. We used two propensity score methods to balance the differences in baseline characteristics between groups and the primary analysis relied on inverse probability of treatment weighting. RESULTS: A total of 543 patients were included. Continuous RRT was the first modality in 269 patients and IHD in 274. Patients receiving CRRT had higher cardiovascular and total-SOFA scores. Inverse probability weighting allowed to adequately balance groups on all predefined confounders. The weighted Kaplan-Meier death rate at day 60 was 54·4% in the CRRT group and 46·5% in the IHD group (weighted HR 1·26, 95% CI 1·01-1·60). In a complementary analysis of less severely ill patients (SOFA score: 3-10), receiving IHD was associated with better day 60 survival compared to CRRT (weighted HR 1.82, 95% CI 1·01-3·28; p < 0.01). We found no evidence of a survival difference between the two RRT modalities in more severe patients. CONCLUSION: Compared to IHD, CRRT as first modality seemed to convey no benefit in terms of survival or of kidney recovery and might even have been associated with less favorable outcome in patients with lesser severity of disease. A prospective randomized non-inferiority trial should be implemented to solve the persistent conundrum of the optimal RRT technique.

RATIONALE: The optimal strategy for initiation of renal replacement therapy (RRT) in patients with severe acute kidney injury in the context of septic shock and acute respiratory distress syndrome (ARDS) is unknown. OBJECTIVES: To examine the effect of an early compared with a delayed RRT initiation strategy on 60-day mortality according to baseline sepsis status, ARDS status, and severity. METHODS: Post hoc analysis of the AKIKI (Artificial Kidney Initiation in Kidney Injury) trial. MEASUREMENTS AND MAIN RESULTS: Subgroups were defined according to baseline characteristics: sepsis status (Sepsis-3 definition), ARDS status (Berlin definition), Simplified Acute Physiology Score 3 (SAPS 3), and Sepsis-related Organ Failure Assessment (SOFA). Of 619 patients, 348 (56%) had septic shock and 207 (33%) had ARDS. We found no significant influence of the baseline sepsis status (P = 0.28), baseline ARDS status (P = 0.94), and baseline severity scores (P = 0.77 and P = 0.46 for SAPS 3 and SOFA, respectively) on the comparison of 60-day mortality according to RRT initiation strategy. A delayed RRT initiation strategy allowed 45% of patients with septic shock and 46% of patients with ARDS to escape RRT. Urine output was higher in the delayed group. Renal function recovery occurred earlier with the delayed RRT strategy in patients with septic shock or ARDS (P < 0.001 and P = 0.003, respectively). Time to successful extubation in patients with ARDS was not affected by RRT strategy (P = 0.43). CONCLUSIONS: Early RRT initiation strategy was not associated with any improvement of 60-day mortality in patients with severe acute kidney injury and septic shock or ARDS. Unnecessary and potentially risky procedures might often be avoided in these fragile populations. Clinical trial registered with www.clinicaltrials.gov (NCT 01932190).