Home > DARE Reviews > Timing of initiation of renal...

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Timing of initiation of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis

X Wang and WJ Yuan.

Review published: 2012.

Link to full article: [Journal publisher]

CRD summary

The authors concluded that early initiation of renal replacement therapy could reduce mortality in patients with acute kidney injury but further research was needed. Due to study limitations, such as a number of low quality studies and small sample sizes, the authors' conclusions regarding the results may not be reliable, but their recommendation for further research seems appropriate.

Authors' objectives

To examine the effects of timing of initiation of renal replacement therapy on mortality in patients with acute kidney injury.

Searching

PubMed, Web of Science and EMBASE were searched from 1990 to August 2011; search terms were reported. No restrictions were set based on language of articles.

Study selection

Eligible studies compared early and late renal replacement therapy for mortality and other clinical outcomes in patients with acute kidney injury. Studies were required to be randomised controlled trials (RCTs), prospective or retrospective designs. Studies that did not provide full research data were excluded.

Comparisons were between early and late treatment and were defined in terms of measures of creatinine or urea. These definitions varied across studies. Mean age (where reported) ranged from 43 to 70 years. Approximately half of the included studies involved patients receiving cardiac surgery. All other included studies were on patients classified as "medical/surgery", sepsis or trauma. Most studies either used continuous renal replacement therapy or a mixed modality (combination of continuous renal replacement therapy, intermittent haemodialysis, sustained low-efficiency dialysis, or peritoneal dialysis). A small number of studies used intermittent haemodialysis alone.

Two authors independently selected studies for inclusion with any differences resolved through discussion.

Assessment of study quality

RCTs were assessed according to the following criteria: sequence generation; allocation concealment; blinded assessment; incomplete outcome data; selective reporting. Non-randomised studies were assessed according to reported criteria for renal replacement therapy initiation, if intervention and control were comparable, and drop-out rates.

The authors did not state how many reviewers conducted quality assessment.

Data extraction

Mortality rates were extracted from each study to calculate risk ratios (RRs) and 95% confidence intervals (CIs).

Two reviewers independently extracted data with any differences resolved through discussion.

Methods of synthesis

A fixed-effect model was used to pool the results from included studies unless substantial heterogeneity was identified. If this was so, a random-effects model was used instead. Statistical heterogeneity was examined using the Q and Ι² statistics. Significant heterogeneity was defined as p<0.1 for the Q statistic. Ι² values were interpreted in the following way: 0 to 24% no heterogeneity; 25 to 49% low heterogeneity; 50 to 74% moderate heterogeneity; greater than or equal to 75% high heterogeneity.

Subgroup analyses were used to compare the effectiveness of renal replacement therapy using different treatment modalities as defined above. Sensitivity analyses were used to examine the effects of study quality and clinical factors on heterogeneity. Sensitivity analyses were undertaken to assess the influence of each study by removing one at a time. A study was considered influential if it resulted in greater than or equal to 20% change on the risk ratio.

Publication bias was visually assessed using a funnel plot.

Results of the review

Fifteen studies were included in the review (2955 patients): three RCTs (143 patients), two prospective (1,480 patients) and 10 retrospective studies (1,332 patients). Both randomised and observational studies were of relatively low quality.

Early renal replacement therapy was associated with a 29% reduction in risk of mortality compared with late renal replacement therapy but with high heterogeneity (RR 0.71; 95% CI 0.59 to 0.86; 15 studies; Ι²=79%).

Subgroup analyses found a similar reduction in mortality for early renal replacement therapy compared with late renal replacement therapy when using continuous renal replacement therapy but with less heterogeneity (RR 0.69; 95% CI 0.56 to 0.84; seven studies, Ι² =33%). There was a 74% reduction in risk of mortality for early renal replacement therapy compared with late renal replacement therapy when using intermittent haemodialysis (RR 0.26; 95% CI 0.15 to 0.45; two studies; Ι²=0%). The pooled effect for the mixed modality suggested no benefit (RR 0.94; 95% CI 0.88 to 1.01; six studies; Ι²=81%) but there was very high heterogeneity.

Sensitivity analyses found no impact when removing one study at a time on continuous renal replacement therapy or mixed modality. However, one study on intermittent haemodialysis found no statistically significant difference.

The authors stated that according to their funnel plot analysis there was no significant evidence of publication bias. But acknowledged it wasn't possible to rule out that such bias was present due to the small number of included studies.

Authors' conclusions

The authors concluded that early initiation of renal replacement therapy could reduce mortality for patients with acute kidney injury. Subgroup analyses found benefit for early initiation whether using continuous renal replacement therapy or intermittent haemodialysis. Further research was required to establish this finding.

CRD commentary

The review question and inclusion criteria were clear. An acceptable range of databases were searched and no language restrictions were applied which may reduce risk of bias. However, there was no indication that unpublished material was sought. Sufficient procedures were used to minimise error and bias for study selection and data extraction although it was unclear if these were also used for quality assessment.

It was unclear whether pooling data from studies of different designs (RCTs, retrospective and prospective studies) was appropriate and may have contributed to the high heterogeneity identified in the meta-analysis. No further analyses were reported that investigated the impact of including different study designs. The authors acknowledged the potential for publication bias.

There was considerable uncertainty in interpreting the results of the meta-analysis due to relatively low quality of included studies (many studies had small sample sizes) and the inclusion of data from different study designs. In addition, some of the larger studies did not find evidence of benefit. Therefore the limitations of this data suggest the authors conclusions regarding the results may not be reliable, but their recommendation for further research seems appropriate.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that further randomised controlled trials were required to confirm the results.

Funding

Not stated.

Bibliographic details

Wang X, Yuan WJ. Timing of initiation of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis. Renal Failure 2012; 34(3): 396-402. [PubMed: 22260302]

Indexing Status

Subject indexing assigned by NLM

MeSH

Acute Kidney Injury /mortality /therapy; Humans; Renal Replacement Therapy /methods; Risk Factors; Survival Rate /trends; Time Factors; World Health

AccessionNumber

12012014211

Database entry date

20/08/2012

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 22260302