This study describes the incidence and long-term mortality rates for critically ill patients with a diagnosis of sARF and the prognosis for long-term renal recovery in a well-defined non-specified population. The annual incidence of sARF in our well-defined population of 11.0 per 100,000 population per year is similar to previous studies from two other continents, 8.0 to 13.4 per 100,000 in Australia and 4.2 to 8.0 per 100,000 in Europe, respectively [5
]. However, two of these studies are potentially prone to selection bias due to failure in clearly defining the geographic boundaries and classification of residency status of the study referral population for which the incidence of sARF was determined [8
], and all these studies are limited as none were able to assess for risk factors, long-term survival or long-term renal recovery prognosis [8
]. Recently, the multi-centre BEST study reported an estimated prevalence for ARF of 5.7% defined by the presence of oliguria and/or azotemia and 4.2% for sARF from 54 ICUs in 23 countries [21
]. While the BEST study is the largest, most comprehensive completed to date and demonstrates a similar occurrence of sARF and in-hospital mortality with our study, it remains prone to selection bias and provided no long-term follow-up. Morgera et al
. reported survival in a cohort of critically ill patients with sARF of 77% and 50% at 6 months and 5 years, respectively; however, this study is potentially prone to selection and information bias due to inclusion of patients receiving only CRRT and incomplete ascertainment of long-term survival status for the entire cohort [6
]. This was unlikely to be a major source of bias in the present study because in the CHR, all critical care services are provided by ICUs included within this surveillance and the CHR is geographically isolated as a single provider of healthcare. Although we could have potentially missed sARF cases that developed in CHR residents while receiving medical attention not available in the CHR (i.e. cardiac, lung or liver transplantation) or while traveling abroad. Likewise, we could have potentially excluded sARF patients with peak serum creatinine <150 μmol/l, resulting in an under-estimation of the incidence of sARF. However, these sources of error, if present, are likely to be small and insignificant. Therefore, this study further establishes the major burden of disease in terms of occurrence, long-term mortality and renal prognosis attributable to sARF in a non-specified population.
Recent consensus recommendations for defining and categorizing acute renal failure have been presented; however, they have not yet been prospectively validated with long-term clinical outcomes such as mortality or renal recovery at 1 year [35
]. This was published after completion of our study; thus, we used as our primary case-definition, acute renal failure severe enough, in the opinion of the treating intensivist, to warrant the initiation of RRT. This definition was selected because the initiation of RRT in critically ill patients has clinical relevance both in terms of severity of illness and for utilization of resources. Thus, a diagnosis of sARF and institution of RRT represents a considerable escalation in patient management. Further, we selected sARF due to simplicity in potentially generalizing our results across similar multi-disciplinary critically ill populations. One potential limitation of this case-definition is defining what factors contribute to the decision by the attending intensivist to initiate RRT, rather than specific indications for RRT. This was not addressed in our study and has yet to be prospectively studied. Another consideration is that, in general, there is likely to be heterogeneity across ICUs regarding who prescribes RRT (i.e. intensivist or nephrologist); however, in this regional critical care system, the decision to initiate RRT was made by the attending intensivist only.
A novel aspect of this study was that several selected underlying conditions were determined to be associated with an increased risk for development of sARF. While previous investigators have suggested that several factors, most notably increasing age, pre-existing renal insufficiency, co-morbid liver or cardiac disease, cancer, sepsis, and greater severity of illness are potential risk factors for sARF, no previous studies were designed to determine and quantify risk in a general population [2
]. Although these estimates provide unbiased univariate population-based risk factors for development of sARF, one potential limitation is the complexity in interpretation without adjustment for potential confounders or effect modifiers. However, our study has shown that critically ill patients who were older, male, and have underlying co-morbid illnesses were at higher risk for developing sARF and may represent a future target population for surveillance, earlier intervention or preventive strategies.
Most studies of sARF in the critically ill population have focused on mortality and renal recovery at ICU and hospital discharge, therefore viewing sARF as an acute and short-term illness [3
]. Assessment of outcomes at these points may underestimate the burden of disease attributable to sARF. Our data indicate that critically ill patients with sARF may remain ill with an increased risk for death for a duration greater than the total ICU or hospital length of stay. This has been similarly shown with sepsis and septic shock, where patients exhibit an increased risk of death following discharge from hospital [37
]. Therefore, clearly defined long-term outcomes as demonstrated in our study, such as case-fatality at 1 year of 64% and rate of renal recovery in survivors of 78%, provide a more informative description of the morbidity and mortality attributable to sARF. Furthermore, the assessment of long-term outcome is important given the high cost associated with RRT in the ICU and continuing chronic RRT [1
]. Likewise, independence from RRT is associated with improved overall quality of life and functional status [1
]. Dependence on RRT at hospital discharge and at 90 days has been estimated to occur in 5% to 33% and 16% of patients, respectively [3
]; however, this does not necessarily translate into long-term RRT dependence. Although the overall rate of dependence on RRT at hospital discharge in our study was comparably higher than other population-based studies, only 8% overall or 22% of survivors at 1 year remained on chronic RRT, an assessment duration more likely associated with permanent need for chronic RRT.
We identified five factors independently associated with death at 1 year (Table ). Although the presence of co-morbid liver disease, higher admission APACHE II score, septic shock, and use of CRRT have been previously suggested, these studies are potentially biased due to the aforementioned limitations in assessment of mortality at ICU or hospital discharge [2
]. An important variable included in this study not previously reported is the contribution of the Charlson co-morbidity index to the overall risk of death [25
]. Previous hospital-based studies have included previous health status as an independent risk for death; however, this was generally assessed by use of the chronic health points component of the APACHE II score or the McCabe scale [10
The need for CRRT was independently associated with death in our study after controlling for the confounding effects of co-morbid illness and disease severity. This is plausible considering that in our clinical practice CRRT is utilized in more unstable patients with great burden of illness, and a poorer expected outcome. Although similarly reported by Chertow et al
], this would appear to contradict several randomized studies suggesting no difference in mortality outcome between CRRT and IHD; however, these studies have methodological concerns, including failure of randomization, inadequate power to assess clinically meaningful differences in primary outcome and, importantly, did not assess the independent effect of dialysis modality on long-term outcomes such as mortality or renal recovery at 1 year [43
In contrast to previous hospital-based studies and our pre-analysis prediction, none of older age, presence of pre-existing renal disease, need for mechanical ventilation or oliguria were independently associated with death [2
The apparent lack of association of chronic renal insufficiency with death at 1 year in our study would appear counterintuitive considering the association of death and co-morbid illness. However, the presence of pre-existing renal disease in these patients likely afforded greater susceptibility to overt renal injury prompting RRT. Although not associated with death, sARF in patients with co-morbid renal disease may represent a cohort less likely to recover renal function and subsequently require chronic RRT as suggested by our study.