Dataset Information

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:

Background

The optimal timing for initiating renal replacement therapy (RRT) in patients with acute kidney injury (AKI) remains controversial.

Methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Feng YM

PROVIDER: S-EPMC5362192 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

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.

Feng Yan-Mei YM Yang Yuan Y Han Xiao-Li XL Zhang Fan F Wan Dong D Guo Rui R

PloS one 20170322 3

<h4>Background</h4>The optimal timing for initiating renal replacement therapy (RRT) in patients with acute kidney injury (AKI) remains controversial.<h4>Methods</h4>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 seconda ...[more]

PMID: 28329026

Similar Datasets

Project description:BackgroundPrevious studies have examined the effect of the initiation time of renal replacement therapy (RRT) in patients with cardiac surgery-associated acute kidney injury (CSA-AKI), but the findings remain controversial. The aim of this meta-analysis was to systematically and quantitatively compare the impact of early versus late initiation of RRT on the outcome of patients with CSA-AKI.MethodsFour databases (PubMed, the Cochrane Library, ISI Web of Knowledge, and Embase) were systematically searched from inception to June 2018 for randomized clinical trials (RCTs). Two investigators independently performed the literature search, study selection, data extraction, and quality evaluation. Meta-analysis and trial sequential analysis (TSA) were used to examine the impact of RRT initiation time on all-cause mortality (primary outcome). The Grading of Recommendations Assessment Development and Evaluation (GRADE) was used to evaluate the level of evidence.ResultsWe identified 4 RCTs with 355 patients that were eligible for inclusion. Pooled analyses indicated no difference in mortality for patients receiving early and late initiation of RRT (relative risk [RR] = 0.61, 95% confidence interval [CI] = 0.33 to 1.12). However, the results were not confirmed by TSA. Similarly, early RRT did not reduce the length of stay (LOS) in the intensive care unit (ICU) (mean difference [MD] = -1.04; 95% CI = -3.34 to 1.27) or the LOS in the hospital (MD = -1.57; 95% CI = -4.62 to 1.48). Analysis using GRADE indicated the certainty of the body of evidence was very low for a benefit from early initiation of RRT.ConclusionEarly initiation of RRT had no beneficial impacts on outcomes in patients with CSA-AKI. Future larger and more adequately powered prospective RCTs are needed to verify the benefit of reduced mortality associated with early initiation of RRT.Trial registrationThis trial is registered with PROSPERO registration number CRD42018084465, registered on 11 February 2018.

Project description:IntroductionOur aim was to investigate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI).MethodsSystematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web of Science and Cochrane Central Registry of Controlled Clinical Trials, and other sources were searched in July 2010. Eligible studies selected were cohort and randomised trials that assessed timing of initiation of RRT in critically ill adults with AKI.ResultsWe identified 15 unique studies (2 randomised, 4 prospective cohort, 9 retrospective cohort) out of 1,494 citations. The overall methodological quality was low. Early, compared with late therapy, was associated with a significant improvement in 28-day mortality (odds ratio (OR) 0.45; 95% confidence interval (CI), 0.28 to 0.72). There was significant heterogeneity among the 15 pooled studies (I(2) = 78%). In subgroup analyses, stratifying by patient population (surgical, n = 8 vs. mixed, n = 7) or study design (prospective, n = 10 vs. retrospective, n = 5), there was no impact on the overall summary estimate for mortality. Meta-regression controlling for illness severity (Acute Physiology And Chronic Health Evaluation II (APACHE II)), baseline creatinine and urea did not impact the overall summary estimate for mortality. Of studies reporting secondary outcomes, five studies (out of seven) reported greater renal recovery, seven (out of eight) studies showed decreased duration of RRT and five (out of six) studies showed decreased ICU length of stay in the early, compared with late, RRT group. Early RRT did not; however, significantly affect the odds of dialysis dependence beyond hospitalization (OR 0.62 0.34 to 1.13, I(2) = 69.6%).ConclusionsEarlier institution of RRT in critically ill patients with AKI may have a beneficial impact on survival. However, this conclusion is based on heterogeneous studies of variable quality and only two randomised trials. In the absence of new evidence from suitably-designed randomised trials, a definitive treatment recommendation cannot be made.

Project description:BackgroundAcute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical prognosis. Renal replacement therapy (RRT) has been widely used in critically ill patients with AKI. However, in patients without urgent indications such as acute pulmonary edema, severe acidosis, and severe hyperkalemia, the optimal timing of RRT initiation is still under debate. We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of early RRT initiation versus delayed RRT initiation.MethodsWe searched databases (PubMed, EMBASE and Cochrane Library) from inception through to July 20, 2020, to identify eligible RCTs. The primary outcome was 28-day mortality. Two authors extracted the data independently. When the I2 values < 25%, we used fixed-effect mode. Otherwise, the random effects model was used as appropriate. TSA was performed to control the risk of random errors and assess whether the results in our meta-analysis were conclusive.ResultsEleven studies involving 5086 patients were identified. Two studies included patients with sepsis, one study included patients with shock after cardiac surgery, and eight others included mixed populations. The criteria for the initiation of RRT, the definition of AKI, and RRT modalities existed great variations among the studies. The median time of RRT initiation across studies ranged from 2 to 7.6 h in the early RRT group and 21 to 57 h in the delayed RRT group. The pooled results showed that early initiation of RRT could not decrease 28-day all-cause mortality compared with delayed RRT (RR 1.01; 95% CI 0.94-1.09; P = 0.77; I2 = 0%). TSA result showed that the required information size was 2949. The cumulative Z curve crossed the futility boundary and reached the required information size. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients and was associated with a higher incidence of hypotension (RR 1.42; 95% CI 1.23-1.63; P < 0.00001; I2 = 8%) and RRT-associated infection events (RR 1.34; 95% CI 1.01-1.78; P = 0.04; I2 = 0%).ConclusionsThis meta-analysis suggested that early initiation of RRT was not associated with survival benefit in critically ill patients with AKI. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients, resulting in a waste of health resources and a higher incidence of RRT-associated adverse events. Maybe, only critically ill patients with a clear and hard indication, such as severe acidosis, pulmonary edema, and hyperkalemia, could benefit from early initiation of RRT.

Project description:BackgroundTiming of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework.MethodsWe performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero-one inflated beta regression.ResultsThe posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] - 3.30%; 3.40%], - 0.39% [95% CrI - 3.46%; 3.00%], and 0.64% [95% CrI - 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of - 3.55 days [95% CrI - 6.38; - 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI - 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66.ConclusionsIn a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.

Dataset Information

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.

Background

Methods

Results

Conclusions

Publications

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.

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