Date Published: March 22, 2017
Publisher: Public Library of Science
Author(s): Yan-mei Feng, Yuan Yang, Xiao-li Han, Fan Zhang, Dong Wan, Rui Guo, Emmanuel A. Burdmann.
The optimal timing for initiating renal replacement therapy (RRT) in patients with acute kidney injury (AKI) remains controversial.
We 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.
We 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.
Although 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.
Acute kidney injury (AKI) is a life-threatening condition in critically ill patients and has a high incidence of morbidity and mortality [1–3]. Although, in recent decades, numerous strategies, including fluid therapy, diuretic treatment, and titration of vasopressors, have been developed to reduce fatal events and improve clinical outcomes, therapies to reverse the natural course of AKI are limited, and protocol-based supportive care is still the cornerstone of treatment .
RRT represents a cornerstone in the management of life-threatening AKI. Several aspects of RRT are now well established, but others remain controversial, especially the optimal timing to initiate RRT. To date, there has been clear consensus that timely RRT is required in life-threatening conditions, such as severe hyperkalemia, marked metabolic acidosis, and/or fluid overload; however, in most critically ill patients with AKI, the decision to initiate RRT is not done mainly on account of overtly life-threatening conditions . Consequently, there are large variations in the timing of RRT initiation in these populations, influencing clinical outcomes. Our meta-analysis, based on the traditional method, provided two conclusions. First, early RRT was not associated with improved clinical outcomes (i.e., reductions in mortality), although this finding should be interpreted with caution, because TSA suggested this evidence may represent a false-negative result. Second, meanwhile, there were no findings to support the idea that early RRT will shorten the ICU LOS and hospital LOS. TSA indicated that the evidence was insufficient and inconclusive.
Conventional meta-analyses that included recent trial data showed that early initiation of RRT in patients with AKI was not associated with decreased mortality, ICU LOS, or hospital LOS. After TSA adjustment for sparse data and multiple update in the cumulative meta-analysis, we were unable to draw definitive conclusions regarding the ideal timing of RRT in patients with AKI. The results of ongoing and future well-designed, large RCTs are needed to clarify this issue.