The effect of early versus late initiation of renal replacement therapy in patients with acute kidney injury: A meta-analysis with trial sequential analysis of randomized controlled trials

Abstract

BackgroundThe optimal timing for initiating renal replacement therapy (RRT) in patients with acute kidney injury (AKI) remains controversial.MethodsWe conducted a meta-analysis with trial sequential analysis (TSA) of randomized controlled trials (RCTs) using PUBMED, Cochrane Library databases, and Web of Science (from January 1, 1985, to August 21, 2016). Adult patients with AKI who received RRT with different timing were included. The primary outcome was mortality. The secondary outcomes were intensive care unit (ICU) length of stay (LOS) and hospital LOS.ResultsWe included 9 RCTs with a total of 1636 participants. No differences between the early RRT group and the late RRT group were found with respect to mortality (38% vs 41.4%; relative risk, 0.93; 95% confidence interval [CI], 0.74–1.18). However, TSA showed that the cumulative Z-curve did not cross either the conventional boundary for benefit or the trial sequential monitoring boundary, indicating insufficient evidence. Similarity, there were no findings of benefits in terms of reduction in the ICU LOS (standard difference in the means, −0.32 days; 95% CI, −0.71 to 0.07 days) and hospital LOS (standard difference in the means, −1.11 days; 95% CI, −2.28 to 0.06 days). Meanwhile, the results of TSA did not confirm this conclusion.ConclusionsAlthough conventional meta-analysis showed that early initiation of RRT in patients with AKI was not associated with decreased mortality, ICU LOS and hospital LOS, TSA indicated that the data were far too sparse to make any conclusions. Therefore, well-designed, large RCTs are needed.

Comparison between watchful waiting strategy and early initiation of renal replacement therapy in the critically ill acute kidney injury population: an updated systematic review and meta-analysis

“…Our present review did not demonstrate a statistically significant survival benefit of early RRT initiation, which is in line with the findings of most previous reviews [5][6][7][8][9][10]. Several studies that revealed positive [13] or negative [14,29,30] effects of early RRT initiation were not included in our meta-analysis.…”

“…Several recent meta-analyses examined the effect of early RRT initiation on patient survival and related outcomes [5][6][7][8][9][10][11]. All but one meta-analysis [11] reported that the early initiation of RRT did not provide a survival advantage (Additional file 1: Table S7).…”

“…Earlier retrospective and prospective studies revealed the survival benefits of early RRT initiation; however, since the AKIKI and ELAIN trials published in 2016, these survival benefits have become debatable. In recent years, several meta-analyses have been published, most of which investigated prospective or retrospective studies owing to the lack of large-scale randomized controlled trials (RCTs), and in these meta-analyses, a definitive conclusion regarding the optimal time of RRT initiation could not be drawn [5][6][7][8][9][10][11]. Conventional indications (refractory fluid overload, acidemia, hyperkalemia, and uremic complication) for RRT initiation are indisputable over several years.…”

Acute kidney injury: Epidemiology, outcomes, complications, and therapeutic strategies

“…Despite previous studies investigating the relationship between mortality and the timing of RRT initiation, it remained controversial whether early initiation of RRT improved outcomes. In 2016, two RCTs and in 2017 nine systematic reviews and meta‐analyses evaluated the optimal timing of RRT initiation for AKI. A multicenter RCT study, the Artificial Kidney Initiation in Kidney Injury (AKIKI) study, conducted in France, showed that there were no significant differences in mortality between early and late initiation of RRT .…”

“…Early initiation of RRT (defined as KDIGO stage 3 AKI) in the AKIKI study corresponded to the delayed arm in the ELAIN study. Turning to the conclusions of nine meta-analyses,[90][91][92][93][94][95][96][97][98] the AKI patients in the RCTs who underwent early initiation of RRT did not show a lower mortality rate than those with late RRT [90][91][92][93][94]96,98.…”