Читать книгу 40 Years of Continuous Renal Replacement Therapy - Группа авторов - Страница 48

Two high-profile trials of strategies for starting RRT in critically ill patients with severe AKI were reported. The Early Versus Late Initiation of RRT In Critically Ill Patients with Acute Kidney Injury (ELAIN) trial was a single-center randomized trial including 231 critically ill patients that evaluated whether early RRT, defined as starting RRT within 8 h of fulfilling KDIGO stage 2 AKI, would improve patient survival as compared to delayed RRT, defined as starting RRT within 12 h of developing KDIGO stage 3 AKI or upon an absolute indication ensuing (Table 4) [21]. All patients in the early group and 91% in the delayed group received RRT, with a median difference in time to initiate being 21 h (interquartile range 18–24). The early RRT intervention conferred a 15.4% absolute reduction in 90-day mortality compared with delayed RRT. Early RRT was found to have greater RRT independence, shorter duration of RRT, and reduced duration of hospitalization. Early RRT also showed an early reduction in 2 pro-inflammatory mediators (interleukin-6, interleukin-8).

The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial was a multicenter randomized trial that evaluated whether a delayed strategy of starting RRT improved survival among 620 critically ill patients with severe AKI (Table 4) [7]. The early strategy started RRT within 6 h of fulfilling KDIGO stage 3 AKI and the delayed strategy started RRT only in response to the development of conventional indications. The early strategy did not improve 60-day mortality; however, RRT utilization was significantly different between the strategies, with only 51% in the delayed strategy receiving RRT compared to 98% in the early strategy. The median difference for starting RRT between strategies was 57 h (interquartile range 25–83). In the delayed strategy, RRT-free days were greater and there was a reduced incidence of catheter-related bloodstream infections. There was no difference in key secondary outcomes including ventilator and vasoactive-free days through day 28, ICU length of stay, hospital length of stay, and RRT dependence at day 60.

The ELAIN and AKIKI trials are important achievements for critical care nephrology and effectively disproved the notion that well-designed trials comparing RRT initiation strategies in the ICU were not feasible. However, there are issues that clinicians should consider when determining how to interpret these findings and incorporate them into clinical practice. First, though these trials were the largest to date to examine RRT timing in critically ill patients with AKI, both were underpowered to detect small but potentially clinically important differences in mortality. AKIKI was designed to detect a 15% absolute reduction in mortality. While conceivable that a delayed strategy may translate into avoidance of RRT-related complications, such survival differences are implausible large. Similarly, ELAIN estimated a sample size based on a 55% mortality at 90-days, assuming an 18% absolute reduction in mortality. Though it demonstrated a mortality reduction with early RRT, ELAIN had a Fragility Index of only 3, implying instability and imprecision in its effect estimate. Second, the thresholds for starting RRT differed between these studies, with the early RRT arms of both trials and the delayed RRT group in ELAIN needing to fulfil KDIGO staging for AKI. This use of relatively static criteria for triggering RRT may have contributed to practice misalignment for starting RRT in both groups of ELAIN and the early strategy of AKIKI. This would raise the speculation on whether a proportion of patients who entered AKIKI and ELAIN were individuals for whom RRT would not be considered in usual practice. This highlights one of the challenges of assessing timing of initiation of RRT in critically ill patients with AKI. The absence of validated clinical or laboratory tools to reliably discriminate patients with a high likelihood of progressing to receive RRT from those in whom recovery is imminent limits the possibility to minimize exposure to unnecessary RRT. AKIKI would imply, at a minimum, that a conservative strategy of “watchful waiting” and starting RRT in response to complications or persistent AKI may be acceptable. Two large multicenter RCTs that add knowledge to this important clinical dilemma are yet to be reported (ClinicalTrials.gov identifiers: IDEAL-ICU [NCT01682590]; STARRT-AKI [NCT02568722]).

Table 4. Summary of published randomized trials evaluating the timing of initiation of RRT in AKI (adapted from [22])