Meta-analysis of frusemide to prevent or treat acute renal failure

Dear Editors:

We read with interest the meta-analysis by Ho et al regarding the use
of frusemide in the prevention or treatment of acute renal failure.1 We
would like to raise several concerns we have with their meta-analysis.

First, the reporting of a pooled analysis of trials that use
frusemide both for the prevention and for the treatment of acute renal
failure may have the consequence of generating confusion and lead to
erroneous conclusions.

Second, the authors have failed to adequately acknowledge the
limitations of the included trials. These trials inconsistently report
both on primary outcomes and adverse effects. Likewise, all patients in
two trials and the majority in another were already receiving renal
replacement therapy at inclusion, thus making pooled estimates on this
outcome invalid.2-4 Furthermore, these trials are generally small and of
poor overall quality. Lastly, most of these trials were published several
decades ago.2 4 5 The approach to, and technical capabilities for,
management of acute renal failure have evolved.

Third, the authors failed to specify a priori criteria for trial
inclusion. As a result, the trial by Brown et al 5 has been included in
their pooled analysis. This trial is a comparison of two frusemide
regimens rather than with a placebo control. They have duplicated the
patients allocated to control in a study by Cantarovich et al for the
assessment of hospital mortality.2 Both of these will unduly influence
the event rates and summary effect estimates. Finally, when assessing
need for renal replacement therapy or the proportion of patients remaining
oliguric, the authors have failed to account for or consider the observed
heterogeneity across studies.

From these findings, we can only conclude that it is not possible to
draw any strong conclusions and that a more cautious interpretation is
warranted, in particular for those trials examining whether treatment with
frusemide impacts outcome. These discrepant findings taken with those
from larger observational studies, suggest there exists a genuine
equipoise on the efficacy of frusemide.6 7

Thus, a large and suitably power multi-centre randomized controlled
trial is needed to definitively resolve the question of the role of
frusemide in the management of acute renal failure. Such a trial should
ideally incorporate clinically relevant and patient-centered outcomes as
well as important secondary outcomes addressing issues of harm,
physiologic effects (i.e. urine output) and dose-response.

Sean M Bagshaw, MD, MSc
Department of Intensive Care, Austin Hospital, Heidelberg, Victoria,
Australia

Rinaldo Bellomo, MD
Department of Intensive Care, Austin Hospital, Heidelberg, Victoria,
Australia

Anthony Delaney, MBBS, MSc
Department of Intensive Care, Royal North Shore Hospital, St. Leonards,
New South Wales, Australia

References:

1. Ho KM, Sheridan DJ. Meta-analysis of frusemide to prevent or treat
acute renal failure. BMJ 2006.

2. Cantarovich F, Fernandez JC, Locatelli A, Perez Loredo J.
Frusemide in high doses in the treatment of acute renal failure.
Postgraduate Medical Journal 1971;47:Suppl:13-7.

3. Cantarovich F, Rangoonwala B, Lorenz H, Verho M, Esnault VL. High-
dose furosemide for established ARF: a prospective, randomized, double-
blind, placebo-controlled, multicenter trial. Am J Kidney Dis
2004;44(3):402-9.

4. Kleinknecht D, Ganeval D, Gonzalez-Duque LA, Fermanian J.
Furosemide in acute oliguric renal failure. A controlled trial. Nephron
1976;17(1):51-8.

5. Brown CB, Ogg CS, Cameron JS. High dose frusemide in acute renal
failure: a controlled trial. Clinical Nephrology 1981;15(2):90-6.

6. Mehta RL, Pascual MT, Soroko S, Chertow GM, Group PS. Diuretics,
mortality, and nonrecovery of renal function in acute renal failure. JAMA
2002;288(20):2547-53.

7. Uchino S, Doig GS, Bellomo R, Morimatsu H, Morgera S, Schetz M, et
al. Diuretics and mortality in acute renal failure. Crit Care Med
2004;32(8):1669-77.

Competing interests:
None declared