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27.

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to survival in hemodialysis patients: an analysis of the Netherlands

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Received for publication: 11.6.07

Accepted in revised form: 1.2.08

Nephrol Dial Transplant (2008) 23: 21262128

doi: 10.1093/ndt/gfn300

Sean M. Bagshaw
Division of Critical Care Medicine, University of Alberta Hospital, University of Alberta, Edmonton, Alberta, Canada

Keywords: acute kidney injury; dialysis; mortality; renal

recovery; stroke

Introduction
Acute kidney injury (AKI) is a heterogeneous syndrome
encompassing a broad spectrum of insults and changes in
function that occur acutely to the kidneys [1]. This syndrome is increasingly encountered in sick hospitalized patients, in particular those admitted to intensive care [24].
This recent increase in the occurrence of AKI probably reflects not only changes in the characteristics of hospitalized
patients (i.e. aging population, greater burden comorbid
disease, severity of illness) but also perhaps a corollary of
achievements made by modern medicine (i.e. more complex interventions, capability of advanced and prolonged
life support) [5].
The development of AKI undoubtedly has important
implications on both short- and long-term morbidity and
mortality [6]. Observational data consistently indicate that
45% of all critically ill patients develop severe AKI and
require initiation of renal replacement therapy (RRT) [79].
This cohort generally has a poor prognosis with mortality
rates often exceeding 60% [79]. Moreover, survivors ofCorrespondence and offprint requests to: Sean M. Bagshaw, MD, MSc,
FRCPC, Division of Critical Care Medicine, University of Alberta Hospital, 3C1.16 Walter C. Mackenzie Centre, 8440-122 Street, Edmonton, Alberta T6G2B7, Canada. Tel: +1-780-407-6755; Fax: +1-780-407-1228;
E-mail: bagshaw@ualberta.ca

ten have protracted stays in ICU and hospital, mild declines

in health-related quality of life, impairments in functional
status and their care consumes enormous health resources
[8,1012]. Despite this, the available literature provides surprisingly little insight into the long-term kidney prognosis
for these patients.
The risk of developing AKI associated with critical illness is likely modified by the presence of pre-morbid
chronic kidney disease (CKD) [13]. Similarly, the development of AKI in those with CKD may modify the natural
history of their illness and accelerate progression towards
end-stage kidney disease (ESKD) and dialysis dependence
[14]. Overall, an estimated 822% of critically ill patients
suffering an episode of severe AKI fail to recover kidney
function during hospitalization and need to be discharged
on chronic dialysis [8,9,15]. Yet, there is a paucity of data
exploring the impact of only partial or incomplete recovery
of function in those surviving critical illness.
In the last few years, a consensus definition and classification scheme for AKI, the RIFLE criteria, has been
developed, validated and shown to have predictive ability,
robustness and clinical relevance across a range of settings
[1620]. This has been a key advance for both clinical care
and research activities in a field that was previously beleaguered by the lack of a standardized definition [21]. The RIFLE criteria also share some commonality with the recently
developed staging criteria for CKD proposed by the Kidney
Disease Outcomes Quality Initiative (K/DOQI) [22]. While
the RIFLE criteria incorporate two outcome stages associated with AKI (i.e. loss, ESKD), these are likely insufficient over the long term for those patients with incomplete


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Short- and long-term survival after acute kidney injury

Nephrol Dial Transplant (2008) 23: Editorial Comments

on short-term survival of both the presence and severity of

AKI complicating acute stroke.
The recovery of kidney function following AKI is an important determinant of morbidity and may have long-term
implications for the health and well-being of patients; however, there has been a dearth of investigations on this topic
[29]. Accordingly, the long-term follow-up study by Schiffl
and Fischer is an important addition to our understanding of
the natural history of AKI in critical illness. These authors
performed a prospective 5-year follow-up study of 425 patients with severe AKI treated with RRT [24]. Notably, no
patient had evidence of pre-existing CKD when defined
by radiologic signs of CKD, persistent abnormal urinalysis
or a decreased estimated glomerular filtration rate (eGFR)
or elevated serum creatinine [>1.3 mg/dL (115 mol/L)].
The RIFLE and K/DOQI CKD criteria were used to define
and describe AKI and long-term recovery and changes to
kidney function, respectively.
There are several interesting findings in this study. First,
the results clearly confirm the poor survival of critically
ill patients with AKI [30]. Moreover, the risk of death appeared to extend well beyond hospital discharge with significant declines in the survival curve not stabilizing until
after 1 year. This long-term risk of death was significantly
higher for those with a higher burden of comorbid disease,
surgical disease and, most importantly, those not achieving
complete recovery of kidney function (hazard ratio 4.14,
P < 0.001). At the time of hospital discharge, only 57%
had achieved complete recovery, defined as an eGFR within
10% of baseline, while the remaining 43% had partial recovery and no patient was receiving chronic dialysis. This
is the first investigation to clearly show how partial recovery of kidney function after an episode of AKI significantly
modifies long-term survival. Such partial recovery would
fulfil the definition for stage 24 CKD. These findings
are rather analogous to studies on the long-term survival
of critically ill septic patients, where an increased risk of
death persists for several months to years beyond the index
hospitalization [31,32].
Second, after the 1-year follow-up, only 27% of those
with partial recovery had meaningful improvements in their
eGFR with 8.2% fully recovering. On the other hand, 10%
had further declines in function. Thus, at 1 year, 26% of
survivors had evidence of CKD (stages 25). At 5 years,
the prevalence of CKD in survivors was only 14%, yet, the
apparent improvement with time was largely attributable to
deaths for those who had partial recovery. This study has
also shown that if patients failed to normalize function by
612 months after their episode of AKI, no further recovery
occurred. Remarkably, only 2% of survivors progressed to
ESKD and required re-initiation of dialysis. However, this
rate may be biased by the re-initiation of RRT not being
offered or willingly considered by all patients and/or patient
death.
Third, critically ill patients with more than one discrete kidney insult (i.e. due to sepsis, shock, nephrotoxins,
surgery) while developing or during recovery from AKI
were significantly less likely to completely recover function (76% for one insult versus 30% for two insults,
P < 0.001). While this finding may seem intuitive to
most, it certainly warrants closer examination. Critically ill

Downloaded from http://ndt.oxfordjournals.org/ by guest on September 25, 2016

recovery and persistent dysfunction yet not requiring dialysis. Accordingly, the RIFLE and K/DOKI criteria likely
have important complementary roles for describing the
short- and long-term clinical consequences of AKI.
Thankfully, there is renewed interest in describing the
epidemiology and short- and long-term clinical outcomes
associated with AKI, as defined by the RIFLE criteria,
across a variety of clinical contexts. Until now, however,
no studies have evaluated the short-term survival of stroke
patients whose course in hospital was complicated by the
development of AKI [23] nor the long-term survival and
kidney prognosis of patients developing severe AKI requiring RRT associated with an admission to intensive care
[24].
Stroke is a leading cause of death and disability [25].
Several factors, including older age, burden of comorbid
disease and type of stroke (i.e. ischaemic, haemorrhagic),
have been shown to modify the short-term prognosis in
acute stroke [25]. Likewise, the presence of CKD has been
found to be both a risk factor for stroke and a determinate
for reduced long-term survival [26,27]. However, there is a
scarcity of literature exploring the impact of development
and severity of AKI on stroke prognosis. Accordingly, the
study by Covic et al. is indeed welcome. These authors have
performed a retrospective 1-year population-based evaluation of consecutive patients hospitalized for first ever CTconfirmed stroke from a single academic centre servicing a
defined geographic population [23]. Of 1090 patients with
stroke, 14.5% developed AKI, defined by the RIFLE criteria, during hospitalization. Of these, 73% fulfilled the risk,
21% the injury and 6% the failure categories, respectively.
The proportion receiving RRT was not reported. Those developing AKI were older, with greater comorbid disease
(i.e. diabetes mellitus, ischaemic heart disease, congestive
heart failure) and had higher baseline serum creatinine values. Unfortunately, however, the authors did not report the
prevalence of CKD in their cohort. The key finding from
this study was the 3.4-fold increased crude risk of 30-day
mortality for those stroke patients whose course was complicated by AKI (43.1% for AKI versus 12.8% for no AKI,
P < 0.001) with the majority of deaths occurring early
(i.e. within 14 days). Moreover, crude mortality was significantly correlated with increasing severity of AKI (30.4%
for risk, 72.7% for injury, 90% for failure, P < 0.001).
While the most significant predictor of death by multivariable analysis was the type of stroke, the impact of AKI was
evident.
There are some potential limitations to these data. Specifically, the RIFLE criteria used in this study omitted the urine
output criteria, baseline serum creatinine was assumed as
the value at admission to hospital and the authors did not
account for in-hospital stroke patients or the impact of severe stroke prompting mechanical ventilation and admission to intensive care. In addition, the observed rate of AKI
may have been confounded by all patients having received
contrast-enhanced imaging that may have predisposed to
contrast-induced nephropathy.
Finally, no data were provided on the timing of occurrence of AKI (i.e. early versus late) in the course of illness,
a factor previously shown to modify survival [28]. Nonetheless, the authors have clearly shown the negative association

2127

2128

Conflicts of interest statement. None declared.

(See related article by H. Schiffl and R. Fischer. Five-year outcomes of
severe acute kidney injury requiring renal replacement therapy. Nephrol
Dial Transplant 2008; 23: 22352241.)
(See related article by A. Covic et al. The impact of acute kidney injury
on short-term survival in an Eastern European population with stroke.
Nephrol Dial Transplant 2008; 23: 22282234.)

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Received for publication: 29.4.08
Accepted in revised form: 5.5.08

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patients are commonly exposed to a host of potential kidney

insults during their illness, some modifiable and some not.
The interaction between repeated insults and new injury to
the kidneys is well recognized, but until now, the impact
on long-term recovery of function has been poorly characterized. In a multi-centre French study, Guerin et al. found
that more than one episode of AKI [defined by serum creatinine >3.4 mg/dL (300 mol/L), urine output <500 mL/
24 h or requirement for RRT] independently predicted lower
survival; however, no data were available on recovery [28].
There are some notable limitations to these data. In particular, the study was conducted over 15 years and largely
reflects the experience of a single academic institution. Yet,
Schiffl and Fischer have expanded our understanding of
the long-term survival and kidney recovery of critically ill
patients with severe AKI.
While these two investigations have undoubtedly broadened our understanding of the short- and long-term impact
of AKI, additional queries naturally arise. Further prospective evaluations of AKI in specific high-risk populations,
such as acute stroke, would clearly appear justified. Similarly, additional studies on the long-term outcome of severe
AKI in critically ill patients are needed, in particular, to further explore the association of multiple insults on recovery
and the natural history of partial recovery.

Nephrol Dial Transplant (2008) 23: Editorial Comments