In 4 years of follow up of 1464 participants in the randomized controlled trial Randomised Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study, Martin Gallagher (The George Institute for Global Health, Sydney, Australia) and colleagues found that patients with acute kidney injury (AKI) in an intensive care unit (ICU) who require renal replacement therapy (RRT; hemodialysis combined with hemofiltration) do not benefit from higher intensity RRT. At a median of 43.9 months follow up, mortality (63% in the low intensity and 63% in the high intensity group), as well as quality of life among those who survived, were the same in both groups. Albuminuria (elevated protein levels in urine, signifying persistent kidney injury) was common among survivors and with equal rates in both groups (40% in the low intensity and 44% in the high intensity group).
The authors state, "Our study highlights the increased long-term risk of death associated with AKI treated with RRT in an ICU. Only one third of randomized patients were alive 3.5 years later, a lower survival than seen in recognised high mortality conditions such as the acute respiratory distress syndrome. Although, in our patients the risk of subsequent maintenance dialysis dependence is low, almost half have evidence of significant proteinuria, portending further risk in the years to come. These findings support the view that survivors of AKI are at increased risk and that closer surveillance may be justified. In addition, our findings suggest that chronic proteinuria reduction strategies, which have shown benefit in some patient groups with proteinuria, may warrant investigation as a therapeutic intervention."
A limitation is that the patients were enrolled in a randomized trial and therefore not necessarily representative of patients in ICUs with AKI in general, and not all patients agreed to long term follow up.
The authors conclude, "In a large cohort of patients with acute kidney injury randomized to differing doses of continuous renal replacement therapy in the ICU, the increased risk of death continues well beyond hospital discharge and is not altered by increased intensity of dialysis. The proportion of patients entering a maintenance dialysis program is small but there is a high prevalence of proteinuria amongst survivors suggesting significant ongoing risk of chronic kidney disease and mortality."
Funding: This study was supported by an Australian Government NHMRC Project Grant (#632811). MG's work on this study was supported by a Jacquot Fellowship from the Royal Australasian College of Physicians. AC was supported by a NHMRC Senior Research Fellowship. JM is supported by a Practitioner Fellowship from the National Health and Medical Research Council. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: RB has received consulting fees from Gambro Pty Ltd. SF has received travel support to present research results at scientific meetings from Eli Lilly, Cardinal Health and CSL Bioplasma. The George Institute for Global Health, an independent not-for-profit institute affiliated with the University of Sydney, has received unrestricted grant support and travel expenses associated with a randomised-controlled trial of fluid resuscitation from Fresenius Kabi. It has also received reimbursement for SF's time as a steering committee member for studies sponsored by Eli Lilly and Eisai. The George Institute has received research funding from Servier, Novartis, Eisai, Merck, Sharp & Dohme, Pfizer Australia, Amgen, Fresenius Kabi Deutschland GmbH, and Sanofi Aventis.
Citation: Gallagher M, Cass A, Bellomo R, Finfer S, Gattas D, et al. (2014) Long-Term Survival and Dialysis Dependency Following Acute Kidney Injury in Intensive Care: Extended Follow-up of a Randomized Controlled Trial. PLoS Med 11(2): e1001601. doi:10.1371/journal.pmed.1001601
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