Correspondence
Intensity of Continuous Renal-Replacement Therapy
N Engl J Med 2010; 362:466-468February 4, 2010
- Article
To the Editor:
In the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study (Oct. 22 issue),1 investigators compared low-intensity versus high-intensity renal-replacement therapy. One of the secondary outcomes was the development of new organ failure. However, the criteria for “nonrenal organ failure” were not provided.
Second, in subgroup analyses, the RENAL study showed that there was no mortality benefit with high-intensity treatment in patients with sepsis, cardiovascular dysfunction, or failure of at least one nonrenal organ. In a study involving 1847 critically ill patients receiving renal-replacement therapy, we recently reported that the number of failed organ systems at the time of such therapy had a significant effect on the rate of death in the intensive care unit, ranging from 38% in patients with one organ failure to 85.6% in patients with more than three failed organ systems.2
The RENAL study was not designed to perform subgroup analyses in patients with three or more associated failed organ systems. The question remains whether renal-replacement therapy should be individualized in patients with acute kidney injury and multiorgan failure and whether there is a role for high-intensity renal-replacement therapy in this group.
Marlies Ostermann, Ph.D., M.D.
Guy's and St. Thomas National Health Service Foundation Trust, London, United Kingdom
marlies@ostermann.freeserve. co. uk Rene W. Chang, M.S.
St. George's University Hospital, London, United KingdomNo potential conflict of interest relevant to this letter was reported.
2 References1
The RENAL Replacement Therapy Study Investigators
Full Text | Web of Science | Medline2
Ostermann M ,Chang RWS . Correlation between parameters at initiation of renal replacement therapy and outcome in patients with acute kidney injury. Crit Care 2009;13:R175-R175
CrossRef | Web of Science | Medline
To the Editor:
The RENAL study on the intensity of continuous renal-replacement therapy in critically ill patients joins the study by the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network1 in clarifying a controversial and important issue. However, we feel that there is a risk of a change in practice that could lead to the undertreatment of patients as a consequence. First, the delivered dose of renal-replacement therapy is commonly lower than the prescribed dose in a range lower than that reported in this study. Second, the most widely used method of renal-replacement therapy is continuous venovenous hemofiltration, which was the method used by 52% of practitioners in a recent worldwide survey.2 The absence of additional doses of dialysis added to hemofiltration may lead to undertreatment that could have an adverse effect on the outcome.3 The use of predilution, which remains a prevalent practice of delivery of replacement solution,4 further decreases the efficacy of the treatment. We urge intensivists not to lower treatment doses before careful evaluation of their practices for renal-replacement therapy.
Matthieu Legrand, M.D.
Didier Payen, M.D., Ph.D.
Lariboisière Hospital, Paris, France
m.legrand@libertysurf. fr No potential conflict of interest relevant to this letter was reported.
4 References1
The VA/NIH Acute Renal Failure Trial Network
Full Text | Web of Science | Medline2
Uchino S ,Bellomo R ,Morimatsu H , et al. Continuous renal replacement therapy: a worldwide practice survey. Intensive Care Med 2007;33:1563-1570
CrossRef | Web of Science | Medline3
Saudan P ,Niederberger M ,De Seigneux S , et al. Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure. Kidney Int 2006;70:1312-1317
CrossRef | Web of Science | Medline4
Ricci Z ,Ronco C ,D'Amico G , et al. Practice patterns in the management of acute renal failure in the critically ill patient: an international survey. Nephrol Dial Transplant 2006;21:690-696
CrossRef | Web of Science | Medline
To the Editor:
The RENAL study investigators conclude that high-intensity continuous renal-replacement therapy in critically ill patients with acute kidney injury had no significant effect on mortality at 90 days. In hemofiltration, solute removal works by convection. A randomized study identified a benefit of a postdilution ultrafiltration rate of more than 35 ml per kilogram of body weight per hour, as compared with 25 ml per kilogram per hour, on mortality.1 In another study, a decreased rate of death was also reported by adding a small dose of diffusion to ultrafiltration at a rate of 25 ml per kilogram per hour.2 The benefit of combining diffusion and convection in hemodiafiltration and the proportion of dialysate flow required remain unknown.
In the RENAL study, diffusion and convection were used simultaneously. It would be of great interest to know what doses of dialysate and ultrafiltration were delivered in each study group. As compared with previous studies,1,2 most patients with severe sepsis would have benefited from higher ultrafiltration rates.1 The postdilution ultrafiltration difference between low-intensity and high-intensity therapy may be insufficient. Another study design with an elicited postfilter solute-removal strategy during continuous renal-replacement therapy, with or without additional diffusion, might give different results.
Damien du Cheyron, M.D., Ph.D.
Jean-Jacques Parienti, M.D., D.T.M.&H.
Caen University Hospital, Caen, France
ducheyron-d@chu-caen.fr No potential conflict of interest relevant to this letter was reported.
2 References1
Ronco C ,Bellomo R ,Homel P , et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000;356:26-30
CrossRef | Web of Science | Medline2
Saudan P ,Niederberger M ,De Seigneux S , et al. Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure. Kidney Int 2006;70:1312-1317
CrossRef | Web of Science | Medline
Author/Editor Response
In response to Ostermann and Chang: we assessed organ dysfunction using the Sequential Organ Failure Assessment (SOFA) score, and the presence of organ failure was identified with the use of the same system (as shown in Table 1 of our article). We agree that severity of illness predicts subsequent mortality; however, there was no evidence from our study that subgroups of sicker patients (as shown in Figure 3 of our article) responded to the intensity of renal-replacement therapy in a different way.
Legrand and Payen are correct in stating that the intensity of delivered renal-replacement therapy is frequently less than that prescribed (as shown in our study) and that clinicians should take this factor into account in their prescription of dose.
In response to du Cheyron and Parienti: we describe the intervention, where we state that study therapy combined dialysate and replacement fluid in a 1:1 ratio so that the subsequent effluent represented a combination of close to 50% diffusive and 50% convective clearance.1,2 It is theoretically possible that a study using analogous doses of effluent and only convective clearance might have shown a different outcome. However, the lack of any outcome difference in our study, despite differences in convective clearance, leads us to conclude that such an outcome is unlikely. We note that the only randomized, controlled study that has supported the view that renal-replacement therapy at a higher convective dose (at 35 or 45 ml per kilogram per hour) leads to a better outcome was a single-center study that has not been replicated elsewhere, used an atypical primary outcome, did not apply a predefined statistical analysis plan,3 and has been indirectly contradicted by two large, multicenter trials.4
Rinaldo Bellomo, M.D.
Austin Hospital, Melbourne, VIC, Australia
ctg@anzics.com. au Alan Cass, M.D., Ph.D.
Martin P. Gallagher, M.D.
George Institute for International Health, Sydney, NSW, AustraliaSince publication of their article, the authors report no further potential conflict of interest.
4 References1
The RENAL Study Investigators
Medline2
The RENAL Study Investigators
CrossRef | Web of Science | Medline3
Finfer S ,Cass A ,Gallagher M ,Lee J ,Su S ,Bellomo R . The RENAL (Randomised Evaluation of Normal vs. Augmented Level Replacement Therapy) study: statistical analysis plan. Crit Care Resusc 2009;11:58-66
Medline4
Bellomo R ,Warrillow SJ ,Reade MC . Why we should be wary of single center-trials. Crit Care Med 2009;37:3114-3119
CrossRef | Web of Science | Medline
