Frailty status among older critically ill patients with severe acute kidney injury

Severe acute kidney injury (AKI) occurs in a significant proportion of critically ill patients. Its presence is a marker of the severity of critical illness, and therefore, severe AKI is often associated with organ dysfunction and with adverse outcomes [1]. Despite important advances in understanding the epidemiology of this condition, the long-term outcomes among survivors of severe AKI are more limited. There is a dearth of information on patient-centred concerns such as functional status, quality of life and socioeconomic status in this population.

A deterioration in health-related quality of life is known to occur in a significant proportion of patients after critical illness, whether they develop AKI or not [2, 3]. However, the presence of severe AKI might herald a higher risk of physical limitations and disability [2]. Frailty is a state of vulnerability characterized by a diminished resilience to external stressors [4] and has been shown to portend greater risk of adverse outcomes in critical illness [5‐7]. Notably, a frail state before critical illness is associated with worse functional status and health-related quality of life among survivors during follow-up [8].

Recent data have suggested AKI may be associated with greater declines in functional status and frailty among survivors of critical illness at 12 months compared to those without AKI [9]. However, there has been no description of how frailty status may evolve among survivors whose course was complicated by severe AKI and whether there are identifiable factors associated with clinical deterioration. Accordingly, the primary aim of this study was to describe frailty status in a prospective cohort of older critically ill patients with severe AKI at 6 months and 12 months. As secondary objectives, we further aimed to describe the association of baseline frailty status and 90-day mortality and identify factors associated with deterioration in frailty status at follow-up.

Among the 499 patients enrolled in the OPTIMAL-AKI study, 462 (93%) had baseline CFS available (median score 4 [IQR 3–5]) and 141 (31%) patients were considered frail. Frailty data were available for 243 patients at 6 months (87% of surviving patients) and 216 patients at 12 months (81% of surviving patients) (Additional file 1: Figure S1). The complete distribution of CFS scores in the cohort is presented in Additional file 1: Table S1. During the 12-month follow-up period, 195 (42%) patients died and 51 (11%) were lost to follow-up. The evolution of frailty status from baseline to 12 months after enrolment is presented in Fig. 1.

We describe the clinical correlates, outcomes and the evolution of frailty status in a large prospective cohort of critically ill older adults with severe AKI. Our data provide new knowledge on implications of frailty status among critically ill patients with severe AKI, a hallmark critical illness severity. Not only was frailty common, present in about 1/3 of patients at baseline, but we also found that frailty portends a higher risk for short and long-term mortality. We showed that clinicians may be less likely to offer RRT to patients perceived as frail. We also found that among survivors not classified as frail at baseline, a substantial proportion of survivors will develop de novo frailty or a worsened frailty status at 6 months and 12 months, while fewer show improvement. We propose that such a transition in functional status may represent a clinically important outcome for patients and/or their families.

Frailty status before critical illness may convey prognostic information and impact care decisions. Most notably, patients with known frailty before critical illness may be perceived differently by clinicians. In addition to clinical characteristics, decision-making at the time where an escalation in the intensity of care is contemplated is likely to be affected by information about previous daily life at home and functional status. We observed that clinicians were less likely to offer RRT for patients with pre-existing frailty and these frail patients were also less likely to receive RRT. However, it must be noted that while baseline frailty status was independently associated with 90-day mortality, the addition of this information to other clinical variables did not result in a meaningful improvement in the prediction of death.

Frailty after critically illness complicated by AKI may be challenging to predict given a “frail state” may be driven by heterogeneous social, cognitive and physical factors that are not readily apparent or measured at ICU admission. While frailty has increasingly been described in general ICU populations [5, 13, 18‐24], it has seldom been the focus among critically ill patients with severe AKI. A single-centre analysis of 317 critically ill patients enrolled in a prospective cohort study reported that AKI was associated with a worsened frailty status at 3 and 12 months after hospital discharge compared to those without AKI [9]. Of note, the original study did not specifically focus on an older cohort and excluded patients with pre-existing cognitive deficits. The proportion of survivors with frailty at 12-month follow-up was greater (59%) than observed in our study while the mortality was lower (17%). Similar findings were reported in a recent multicentre observational study of unselected critically ill adults which reported a higher rate of transition to a newly frail state (40%) at 12 months of follow-up, albeit with a much lower mortality rate (25%)[24].

Severe AKI may identify patients more susceptible to prolonged ICU stay [25] and for which rehabilitation may be hampered by the use of RRT [26, 27]. However, neither the duration of ICU stay nor the receipt of RRT were associated with worsened frailty at follow-up in our cohort. Similarly, while it may be evident that a higher burden of baseline chronic disease or the higher acuity of illness should increase the risk of frailty [28], we did not observe this association. Our observations suggest that the risk of developing frailty, a complex multi-dimensional syndrome, cannot be simply extrapolated using simple baseline information. Interestingly, we also report that a substantial proportion of patients showed improvement in their CFS score and frailty status between 6 months and 12 months after critical illness, although the clinical characteristics associated with these transitions remain unclear. From a research perspective, these observations would imply that assessment of frailty status should be extended further than 6 months after critical illness to identify opportunities for intervening to improve outcomes and prevent further functional decline in these patients.

This work has several strengths. Its prospective design minimized recall bias in the assessment of frailty and permitted repeated standardized assessments using a validated scale. Furthermore, data were collected at multiple Canadian centres representative of a diverse critical care population thereby improving generalizability. Also, loss to follow-up (11%) was lower than previous studies [9, 24]. Additionally, this study was the first to study frailty in a population comprised exclusively of AKI patients and report data from an important number of patients with severe AKI. Furthermore, data collection was performed in a relatively short period of time (< 2 years) minimizing the potential impact of changing practice patterns. Finally, this study includes information about the willingness to deliver RRT in the setting of severe AKI which reflects the perceptions of bedside clinicians. The latter is likely to be impacted by information about pre-existing level of functioning prior to hospitalization, which is correlated to frailty.

We recognize some key limitations. Missing frailty assessments at follow-up, although not overly frequent, may have resulted in information bias. Furthermore, while the CFS is a validated tool, it is not the only method to assess frailty and CFS was not compared to other tools such as multi-domain assessments [29]. Most importantly, a single CFS assessment does not provide information about the functional trajectory in the months preceding critical illness which may carry important clinical implications [30, 31]. Inter-rater reliability assessment of CFS was not performed during the study but has previously been shown to be good in similar settings [12]. Second, potentially important socio-demographic and clinical variables that are known to impact frailty status were not collected [32]. Furthermore, most variables capturing illness acuity were recorded at study enrolment while factors occurring later during or after the index hospital stay might impacted frailty status. The lack of serial measures of these time-varying characteristics might explain the lack of associations with frailty status at follow-up. Lastly, the absence of an appropriate control group without severe AKI does not enable us to assess whether frailty develops more frequently in among critically ill survivors with severe AKI.

In this large multicentre prospective cohort study of older adults with severe AKI, we describe the evolution of frailty status from baseline to 12 months of follow-up and describe that transition to frail state occurs in a substantial proportion of survivors. Although the precise clinical risk factors for this deterioration remain elusive, this information may orient future investigations aimed at better understanding and improving functional outcomes in critically ill patients with severe AKI.