Original Investigation
Pathogenesis and Treatment of Kidney Disease
Timing of Renal Replacement Therapy Initiation in Acute Renal Failure: A Meta-analysis

https://doi.org/10.1053/j.ajkd.2008.02.371Get rights and content

Background

Some studies have suggested that early institution of renal replacement therapy (RRT) might be associated with improved outcomes in patients with acute renal failure (ARF).

Study Design

A systematic review and meta-analysis of randomized controlled trials and cohort comparative studies to assess the effect of early RRT on mortality in patients with ARF.

Setting & Population

Hospitalized adult patients with ARF.

Selection Criteria for Studies

We searched several databases for studies that compared the effect of “early” and “late” RRT initiation on mortality in patients with ARF. We included studies of various designs.

Intervention

Early RRT as defined in the individual studies.

Outcomes

The primary outcome measure was the effect of early RRT on mortality stratified by study design. The pooled risk ratio (RR) for mortality was compiled using a random-effects model. Heterogeneity was evaluated by means of subgroup analysis and meta-regression.

Results

We identified 23 studies (5 randomized or quasi-randomized controlled trials, 1 prospective and 16 retrospective comparative cohort studies, and 1 single-arm study with a historic control group). By using meta-analysis of randomized trials, early RRT was associated with a nonsignificant 36% mortality risk reduction (RR, 0.64; 95% confidence interval, 0.40 to 1.05; P = 0.08). Conversely, in cohort studies, early RRT was associated with a statistically significant 28% mortality risk reduction (RR, 0.72; 95% confidence interval, 0.64 to 0.82; P < 0.001). The overall test for heterogeneity among cohort studies was significant (P = 0.005). Meta-regression yielded no significant associations; however, early dialysis therapy was associated more strongly with lower mortality in smaller studies (n < 100) by means of subgroup analysis.

Limitations

Paucity of randomized controlled trials, use of variable definitions of early RRT, and publication bias preclude definitive conclusions.

Conclusion

This hypothesis-generating meta-analysis suggests that early initiation of RRT in patients with ARF might be associated with improved survival, calling for an adequately powered randomized controlled trial to address this question.

Section snippets

Search for Relevant Studies

We searched the medical literature for clinical studies examining the timing of RRT and mortality in patients with ARF, starting in 1960 because the first artificial kidney (Kolff twin coil tank) became commercially available in 195635 and the concept of prophylactic dialysis was not introduced until 1960.14 Primary sources used to identify clinical studies included: (1) a MEDLINE literature search in PubMed using the MeSH database search terms “kidney failure, acute,” “renal insufficiency,

Study Characteristics

A total of 4,182 potentially relevant citations were identified and screened, of which 4,178 originated from MEDLINE. From these, 57 articles were retrieved for detailed evaluation, and 34 were excluded based on eligibility criteria (Fig 1). Twenty-three studies fulfilled the selection criteria and included 4 randomized controlled trials (RCTs),24, 27, 33, 37 1 quasi-RCT (with stratification and sequential treatment assignment),20 1 prospective comparative cohort study,32 16 retrospective

Discussion

First introduced more than 5 decades ago, early dialysis was used to describe the initiation of RRT before nitrogenous waste products had reached some arbitrary predefined cutoff value and irrespective of traditional clinical indications.11, 12, 13, 14, 15, 16, 17, 18, 19, 20 Over the years, studies addressing the potential value of this approach have had poor experimental design, including a paucity of RCTs, inadequate sample size, and use of variable definitions for early institution of

Acknowledgements

Support: Dr Jaber is supported by grants from the National Institutes of Health (DK065102 and R03DK077751). Dr Liangos is supported by a grant from the American Heart Association (AHA #0535367N).

Financial Disclosure: None.

References (53)

  • I. Durmaz et al.

    Prophylactic dialysis in patients with renal dysfunction undergoing on-pump coronary artery bypass surgery

    Ann Thorac Surg

    (2003)
  • R. DerSimonian et al.

    Meta-analysis in clinical trials

    Control Clin Trials

    (1986)
  • J.T. Balslov et al.

    A survey of 499 patients with acute anuric renal insufficiencyCauses, treatment, complications and mortality

    Am J Med

    (1963)
  • R. Vanholder et al.

    Review on uremic toxins: Classification, concentration, and interindividual variability

    Kidney Int

    (2003)
  • R.A. Star

    Treatment of acute renal failure

    Kidney Int

    (1998)
  • B. Jaber et al.

    Effect of biocompatibility of hemodialysis membranes on mortality in acute renal failure: A meta-analysis

    Clin Nephrol

    (2002)
  • A. Alonso et al.

    Biocompatible hemodialysis membranes for acute renal failure

    Cochrane Database Syst Rev

    (2005)
  • J.A. Kellum et al.

    Continuous versus intermittent renal replacement: A meta-analysis

    Intensive Care Med

    (2002)
  • G. Teehan et al.

    Dialysis membrane and modality in acute renal failure: Understanding discordant meta-analyses

    Semin Dial

    (2003)
  • P. Anthonisen et al.

    Clinical experience with the Skeggs-Leonards type of artificial kidney; Report of 46 consecutive patients

    Lancet

    (1956)
  • P.F. Salisbury

    Timely versus delayed use of the artificial kidney

    Arch Intern Med

    (1958)
  • B.H. Scribner

    Role of the artificial kidney in management of acute renal failure

    Northwest Med

    (1959)
  • P.E. Teschan et al.

    Prophylactic hemodialysis in the treatment of acute renal failure

    Ann Intern Med

    (1960)
  • R.P. Fischer et al.

    Early dialysis in the treatment of acute renal failure

    Surg Gynecol Obstet

    (1966)
  • W.J. Kolff

    First clinical experience with the artificial kidney

    Ann Intern Med

    (1965)
  • S. Kornhall

    Acute renal failure in surgical disease with special regard to neglected complicationsA retrospective study of 298 cases treated during the period 1960-1968

    Acta Chir Scand Suppl

    (1971)

    • Cited by (0)

    Originally published online as doi:10.1053/j.ajkd.2008.02.371 on June 19, 2008.

    Because an author of this manuscript is an editor for AJKD, the peer-review and decision-making processes were handled entirely by an Associate Editor (Jonathan Craig, MD, PhD, University of Sydney) who served as Acting Editor-in-Chief. Details of the journal's procedures for potential editor conflicts are given in the Editorial Policies section of the AJKD website.

    View full text
    Copyright © 2008 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.