Open Access

Accounting for single center effects in systematic reviews cannot be overlooked

  • Bruno Adler Maccagnan Pinheiro Besen1, 2Email author,
  • Marcelo Park1 and
  • Antonio Paulo NassarJr1, 3
Critical Care201721:241

https://doi.org/10.1186/s13054-017-1804-0

Published: 15 September 2017

We read with interest the recently published systematic review and meta-analysis on timing of renal replacement therapy (RRT) in cardiac surgery patients [1]. However, we are worried with the presented results and the possible impact on clinical practice of this study.

The author’s have included two studies that were not related to the inclusion criteria. Lange et al.’s study [2] was merely descriptive and assessed risk factors for worse outcomes, with no mention of early or late initiation of RRT. Li et al.’s study [3] compared different doses of RRT and reported no differences in mean time (h) to initiation of RRT. Furthermore, the authors included a study in the analysis that was not related to cardiac surgery [4].

In our opinion, these downsides are a threat to the internal validity of the systematic review and preclude any meaningful interpretation of results. Even more so, the author’s have not reported a subgroup analysis to investigate single-center effects, which are known to bias results from meta-analysis [5]. To address this, we have performed a random-effects meta-analysis excluding studies that were not related to the systematic review’s original inclusion criteria and with a subgroup analysis to investigate single center effects (Fig. 1). When considering only multicenter trials, the point estimate is pulled to the null and the results are neutral. This is unsurprising since recent systematic reviews comprising mixed populations of critically ill patients have not shown any beneficial effect when pooling results across randomized clinical trials at low risk of bias.
Fig. 1

Forest plot, stratified according to the number of centers of the original studies. Studies not fulfilling inclusion criteria of the systematic review’s study question [1] were not included in this analysis. RRT renal replacement therapy, RR risk ratio, CI confidence interval

Therefore, we believe the results of this meta-analysis should be cautiously interpreted before widespread adoption of early RRT as a standard practice, pending the results of adequately designed higher-quality randomized clinical trials.

Authors’ response

  • Gaosi Xu
  • We are grateful to Professor Besen for his comments. First of all, we agree it is preferable for a meta-analysis to include original multi-centered randomized controlled trials; however, well-designed studies such as these are unfortunately lacking in cardiac surgery. Second, it can be seen in Fig. 1 that the heterogeneity of the multi-centered trials included is moderate (67.7%), and that only three trials are studied. Third, in Li et al.’s study [3], one of the purposes of the research was to investigate timing to RRT initiation, and the indication for RRT was urine output < 240 mL/12 h regardless of other symptoms. Li et al.’s study compared different doses of RRT as well as timing to RRT initiation, and the high-dose group received early RRT [3]. In other words, the study indicated that an early higher continuous veno-venous hemofiltration dose was associated with better in-hospital and long-term survival [3]. As for the study by Kleinknecht et al. [4], we think that this can be included in our meta-analysis as patients who suffered from acute kidney injury in post-cardiac surgery are included. Fourth, we performed a meta-regression in our meta-analysis [1] but did not find the sources of heterogeneity, so no other subgroup analysis was done. Last but not least, the results of the analysis of early versus late RRT initiation (Additional file 1) and subgroup analysis of the timing to early RRT initiation (Additional file 2) are consistent with our original results even after exclusion of these three studies [24]. The results are therefore that early RRT initiation decreases 28-day mortality, especially when started within 24 h, in patients with severe acute kidney injury after cardiac surgery.

    Notes

    Abbreviations

    RRT: 

    Renal replacement therapy

    Declarations

    Acknowledgements

    Not applicable.

    Funding

    There was no funding for this manuscript.

    Availability of data and materials

    The data that support the findings of this study were extracted from the originally published systematic review and original articles from the references list.

    Authors’ contributions

    BAMPB wrote the manuscript and conducted the statistical analysis presented in Fig. 1. MP and APNJ contributed with intellectual input and writing of the manuscript. All authors read and approved the final manuscript.

    Authors’ information

    All authors are currently attending physicians also involved with research and teaching activities.

    Ethics approval and consent to participate

    Not applicable.

    Consent for publication

    Not applicable.

    Competing interests

    The authors declare that they have no competing interests.

    Publisher’s Note

    Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

    Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

    Authors’ Affiliations

    (1)
    Medical Intensive Care Unit, Medical Emergencies Discipline, Hospital das Clínicas, University of São Paulo Medical School
    (2)
    Intensive Care Unit, Hospital da Luz
    (3)
    Intensive Care Unit, A.C. Camargo Cancer Center

    References

    1. Zou H, Hong Q, Xu G. Early versus late initiation of renal replacement therapy impacts mortality in patients with acute kidney injury post cardiac surgery: a meta-analysis. Crit Care. 2017;21(1):150.View ArticlePubMedPubMed CentralGoogle Scholar
    2. Lange HW, Aeppli DM, Brown DC. Survival of patients with acute renal failure requiring dialysis after open heart surgery: early prognostic indicators. Am Heart J. 1987;113(5):1138–43.View ArticlePubMedGoogle Scholar
    3. Li SY, Yang WC, Chuang CL. Effect of early and intensive continuous venovenous hemofiltration on patients with cardiogenic shock and acute kidney injury after cardiac surgery. J Thorac Cardiovasc Surg. 2014;148(4):1628–33.View ArticlePubMedGoogle Scholar
    4. Kleinknecht D, Jungers P, Chanard J, Barbanel C, Ganeval D. Uremic and non-uremic complications in acute renal failure: Evaluation of early and frequent dialysis on prognosis. Kidney Int. 1972;1(3):190–6.View ArticlePubMedGoogle Scholar
    5. Dechartres A, Boutron I, Trinquart L, Charles P, Ravaud P. Single-center trials show larger treatment effects than multicenter trials: evidence from a meta-epidemiologic study. Ann Intern Med. 2011;155(1):39–51.View ArticlePubMedGoogle Scholar

    Copyright

    © The Author(s). 2017

    Advertisement