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Continuous renal replacement therapy

Marcello Tonelli, MD SM^*, Braden Manns, MD MSc, Neesh Pannu, MD^*, Scott Klarenbach, MD MSc^* and Kailash Jindal, MD^*

^* University of Alberta, Edmonton, Canada
University of Calgary, Calgary, Canada, E-mail: marcello.tonelli{at}ualberta.ca

To the Editor:

We read the article by Jacka et al.¹ with interest. This manuscript is provocative and novel but raises potentially significant methodological questions.

First, the issue of crossovers between treatment groups makes it difficult to conclude which modality was responsible for favourable or adverse outcomes. Was continuous renal replacement therapy (CRRT) still associated with better renal recovery if only patients treated with a single modality were included?

Second, comparing renal recovery in survivors is of questionable validity as the sole renal outcome. Specifically, the "advantage" of CRRT was observed only after excluding those who died – and as Jacka et al. note, death in the intensive care unit (ICU) was significantly more frequent in the CRRT group. Since death and dialysis-dependence are competing risks, the composite of both outcomes would seem more appropriate. This outcome does not appear to significantly differ between the two modalities, which is unsurprising. Although the largest randomized study to date actually showed significantly increased in-hospital mortality due to CRRT use,² this may not have resulted from the effect of treatment per se. As noted by Jacka et al. in their article, the underlying illness probably influences prognosis to a far greater extent than the dialytic modality.

Third, impaired kidney function at baseline is strongly associated with the need for chronic dialysis in people with acute renal failure.³ In the study by Jacka et al., patients who received intermittent hemodialysis (IHD) had significantly higher serum creatinine at ICU admission, suggesting that they were more likely to have pre-morbid chronic renal insufficiency. Unfortunately, analyses evaluating renal recovery by treatment modality did not control for this difference, which may have influenced the findings.

Finally, a pooled analysis of four randomized studies including more than 400 patients showed no renal benefit of CRRT (and a slight trend towards harm).⁴ Although meta-analysis has its limitations, none of the four included studies showed a renal benefit of CRRT. Jacka et al. do not discuss why their retrospective study might differ from the available randomized trials. We speculate that the discrepancy is due to bias resulting from the non-randomized design.

Multiple non-randomized studies over the last 20 years have been used to support the theoretical benefits of CRRT, and to justify its higher costs. However, randomized studies have not demonstrated that CRRT is superior. Even for surrogate outcomes such as intradialytic hypotension, no good quality data support the use of this indisputably more expensive treatment.

We agree with Jacka et al. that larger randomized trials should be performed, but respectfully disagree that their article helps to inform debate in the interim. Since the best available data do not indicate that dialytic modality influences outcome in critically ill patients, we suggest that the least costly therapy should be used until new randomized trials demonstrate otherwise.

References

1 Jacka MJ, Ivancinova X, Gibney RT. Continuous renal replacement therapy improves renal recovery from acute renal failure. Can J Anesth 2005; 52: 327–32.[Abstract/Free Full Text]

2 Mehta RL, McDonald BR, Babbai FB, et al. A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure. Kidney Int 2001; 60: 1154–63.[Medline]

3 Silvester W, Bellomo R, Cole L. Epidemiology, management, and outcome of severe acute renal failure of critical illness in Australia. Crit Care Med 2001; 29: 1910–5.[Medline]

4 Tonelli M, Manns B, Feller-Kopman D. Acute renal failure in the intensive care unit: a systematic review of the impact of dialytic modality on mortality and renal recovery. Am J Kidney Dis 2002; 40: 875–85.[Medline]

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