Long-term outcome in ICU patients with acute kidney injury treated with renal replacement therapy: a prospective cohort study

De Corte et al. Critical Care (2016) 20:256 DOI 10.1186/s13054-016-1409-z RESEARCH Open Access Long-term outcome in ICU patients with acute kidney injury treated with renal replacement therapy: a prospective cohort study Wouter De Corte1,2*, Annemieke Dhondt3, Raymond Vanholder3, Jan De Waele1,4, Johan Decruyenaere1, Veerle Sergoyne5, Joke Vanhalst6, Stefaan Claus3 and Eric A. J. Hoste1,4 Abstract Background: In intensive care unit (ICU) patients, acute kidney injury treated with renal replacement therapy (AKI-RRT) is associated with adverse outcomes. The aim of this study was to evaluate variables associated with long-term survival and kidney outcome and to assess the composite endpoint major adverse kidney events (MAKE; defined as death, incomplete kidney recovery, or development of end-stage renal disease treated with RRT) in a cohort of ICU patients with AKI-RRT. Methods: We conducted a single-center, prospective observational study in a 50-bed ICU tertiary care hospital. During the study period from August 2004 through December 2012, all consecutive adult patients with AKI-RRT were included. Data were prospectively recorded during the patients’ hospital stay and were retrieved from the hospital databases. Data on long-term follow-up were gathered during follow-up consultation or, in the absence of this, by consulting the general physician. Results: AKI-RRT was reported in 1292 of 23,665 first ICU admissions (5.5 %). Mortality increased from 59.7 % at hospital discharge to 72.1 % at 3 years. A Cox proportional hazards model demonstrated an association of increasing age, severity of illness, and continuous RRT with long-term mortality. Among hospital survivors with reference creatinine measurements, 1-year renal recovery was complete in 48.4 % and incomplete in 32.6 %. Dialysis dependence was reported in 19.0 % and was associated with age, diabetes, chronic kidney disease (CKD), and oliguria at the time of initiation of RRT. MAKE increased from 83.1 % at hospital discharge to 93. 7 % at 3 years. Multivariate regression analysis showed no association of classical determinants of outcome (preexisting CKD, timing of initiation of RRT, and RRT modality) with MAKE at 1 year. Conclusions: Our study demonstrates poor long-term survival after AKI-RRT that was determined mainly by severity of illness and RRT modality at initiation of RRT. Renal recovery is limited, especially in patients with acute-on-chronic kidney disease, making nephrological follow-up imperative. MAKE is associated mainly with variables determining mortality. Keywords: Acute kidney injury (AKI), Long-term survival, Major adverse kidney events (MAKE), Renal recovery, Renal replacement therapy (RRT), Modality of renal replacement therapy, Timing of renal replacement therapy, Acute-on-chronic kidney failure * Correspondence: 1 Department of Intensive Care Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Gent, Belgium 2 Department of Anesthesia and Intensive Care Medicine, AZ Groeninge Hospital, Kortrijk, Belgium Full list of author information is available at the end of the article © 2016 The Author(s). Open Access This 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. De Corte et al. Critical Care (2016) 20:256 Background Acute kidney injury (AKI) is a frequent finding in intensive care unit (ICU) patients, with a prevalence of approximately 40–57 % when defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. AKI treated with renal replacement therapy (AKI-RRT) occurs in approximately 13 % of ICU patients [1, 2]. It is associated with adverse outcomes such as increased length of stay, short- and long-term mortality, and end-stage renal disease (ESRD). In the past, AKI was considered a surrogate marker for severity of illness, and patient mortality was considered a consequence of the underlying disease [3]. However, there is an abundance of epidemiological data demonstrating that AKI in itself leads to adverse outcomes. This is so for the most severe form of AKI, where patients are treated with RRT [4, 5]. In addition, small decreases in kidney function are associated with increased short-term mortality. Further, the prevalence of preexisting chronic kidney disease (CKD) is increasing among patients admitted to the ICU. CKD may lower the threshold for developing AKI, and acute-on-chronic kidney disease is associated with adverse outcomes [3–7]. Further, even mild AKI may predispose patients to CKD, and thus it increases the risk of subsequent AKI events and finally ESRD [8–10]. So, AKI can be considered both the cause and the consequence of CKD, and AKI and CKD therefore are considered interconnected and integrated syndromes [6]. The association of CKD with mortality remains a matter of debate. On one hand, a recent large registry study demonstrated an association of CKD and death [7]. On the other hand, critically ill patients with AKI-RRT who had CKD were reported to have lower short-term mortality than those without preexisting CKD [9, 11–14]. Another factor that may impact long-term outcomes is modality of RRT. Observational studies suggest that continuous RRT (CRRT) is associated with better kidney outcomes, more specifically with less need for chronic dialysis [8, 9]. However, prospective randomized studies could not demonstrate a survival benefit of CRRT compared with intermittent therapies [10, 11]. Finally, optimal timing of initiation of RRT is unclear. RRT is initiated early in the absence of serious complications of AKI and may therefore have some advantages. The late and more conservative approach takes into account that some patients with severe AKI might recover kidney function spontaneously without starting RRT, thereby avoiding adverse events linked to RRT [12]. Until recently, studies of AKI in ICU patients were focused on conventionally accepted short-term outcomes such as mortality at day 30 or at ICU and hospital discharge. However, these endpoints may underestimate the true burden of kidney disease. In light of the increasing focus on long-term outcomes, researchers in several Page 2 of 13 studies have investigated the links between AKI, CKD, and ESRD [13, 14]. By way of analogy to major adverse cardiovascular events, this led to the introduction of the composite endpoint major adverse kidney events (MAKE) [15]. MAKE is a composite of death, ESRD needing dialysis, and incomplete kidney recovery, defined as a 25 % decrease of (...truncated)