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Continuous renal replacement therapy is associated with less chronic renal failure than intermittent haemodialysis after acute renal failure

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Acute renal failure can be treated with continuous renal replacement therapy (CRRT) or intermittent haemodialysis (IHD). Whether this choice affects renal recovery has been debated, since it has implications on quality of life and costs. Our objective was to determine the impact of CRRT and IHD on renal recovery. Nationwide retrospective cohort study between the years 1995 and 2004. Follow-up ranged between 3 months and 10 years. Thirty-two Swedish intensive care units. Eligible subjects were adults treated in Swedish general intensive care units with RRT. A total of 2,642 patients from 32 ICUs were included. We then excluded patients with end-stage renal disease (252) and patients lacking a diagnosis in the in-patient register (188). Thus, 2,202 patients were studied. Follow-up was complete. None. The primary outcome was renal recovery. Secondarily we studied the mortality of the cohort. There were no differences between IHD and CRRT patients regarding baseline characteristics, such as age, sex and comorbidities. Of the 1,102 patients surviving 90 days after inclusion in the cohort, 944 (85.7%) were treated with CRRT and 158 (14.3%) were treated with IHD. Seventy-eight patients (8.3%; confidence interval, CI, 6.6-10.2), never recovered their renal function in the CRRT group. The proportion was significantly higher among IHD patients, where 26 subjects or 16.5% (CI 11.0-23.2) developed need for chronic dialysis. The use of CRRT is associated with better renal recovery than IHD, but mortality does not differ between the groups.
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Intensive Care Med
DOI 10.1007/s00134-007-0590-6
ORIGINAL
Max Bell
SWING
Fredrik Granath
Staffan Schön
Anders Ekbom
Claes-Roland Martling
Continuous renal replacement therapy
is associated with less chronic renal failure
than intermittent haemodialysis after acute
renal failure
Receiv ed: 10 September 2006
Accepted: 22 February 2007
© Springer-Verlag 2007
Electronic supplementary material
The online version of this article
(doi:10.1007/s00134-007-0590-6) contains
supplementary material, which is av ailable
to authorized users.
M. Bell (u) · C.-R. Martling
Karolinska University Hospital, Department
of Anaesthesiology and Intensive Care,
171 76 Solna, Sweden
e-mail: max.bell@karolinska.se
SWING
SWING is the Swedish Intensive care
Nephrology Group, whose member
hospitals are tabulated in the appendixes,
n.a., Sweden
F. Granath · A. Ekbom
Karolinska University Hospital, Department
of Medicine, Clinical Epidemiology Unit,
Solna, Sweden
S. Schön
Kärnhospital, Swedish Register of Active
Treatment of Uraemia, Department
of Nephrology,
Skövde, Sweden
Abstract Objective: Acute renal
failure can be treated with continuous
renal replacement therapy (CRRT)
or intermittent haemodialysis (IHD).
Whether this choice affects renal
recovery has been debated, since it
has implications on quality of life and
costs. Our objective was to determine
the impact of CRRT and IHD on
renal recovery. Design: Nationwide
retrospective cohort study between
the years 1995 and 2004. Follow-up
ranged between 3 months and 10
years. Setting: Thirty-two Swedish
intensive care units. Patients and
participants: Eligible subjects were
adults treated in Swedish general
intensive care units with RRT. A total
of 2,642 patients from 32 ICUs were
included. We then excluded p atients
with end-stage renal disease (252)
and patients lacking a diagnosis in
the in-patient register (188). Thus,
2,202 patients were studied. Follow-
up was complete. Interventions:
None. Measurements and results:
The primary outcome was renal
recovery. Secondarily we studied
the mortality of the cohort. There
were no differences between IHD
and CRRT patients regarding baseline
characteristics, such as age, sex and
comorbidities. Of the 1,102 patients
surviving 90 days after inclusion in
the cohort, 944 (85.7%) were treated
with CRRT and 158 (14.3%) were
treated with IHD. Seventy-eight
patients (8.3%; confidence interval,
CI, 6.6–10.2), never recovered their
renal function in the CRRT group.
The proportion was significantly
higher among IHD patients, where
26 subjects or 16.5% (CI 11.0–23.2)
developed need for chronic dialysis.
Conclusions: The use of CRRT is
associated with better renal recovery
than IHD, but mortality does not
differ between the groups.
Keywords Kidney failure, acute ·
Kidney failure, chronic · Hemo-
dialysis · Intensive care · Outcome
studies
Introduction
Acute renal failure (ARF) requiring renal replacement
therapy (RRT) is common in critically ill patients treated
in the intensive care unit (ICU) [1]. The condition often
develops as one manifestation of multiple organ f ailure
and is associated with a poor prognosis—the published
ICU and hospital mortality rates range from 35% to over
80% [2–4]. The incidence rates for RRT-treated ARF in
the general population ranges from 18 to 80 cases/1 mil-
lion per year in recent studies [3, 5, 6]. There is insufficient
knowledge regarding long term outcome of these patients,
measured as renal recovery. End-stage renal disease
(ESRD) is associated with both costs and impairment of
quality of life, making this a paramount issue. The vast
discrepancy between reports—some state that one-third of
surviving ARF patients had irreversible renal dysfunction
and were dependent on dialysis after ICU discharge [7, 8],
while others give figures of around 2–8% [2, 3, 9]—raises
questions. It should b e noted that earlier studies used ICU
discharge as a cut-off and only included patients treated
with intermittent renal replacement therapy (IHD).
The haemodynamic instability associated with IHD
has been found to have an adverse effect on renal recov-
ery [10–12]. This fact, in conjunction with the reports on
ICU renal recovery data, led us to hypothesise that the
choice of continuous or intermittent RRT affects renal out-
come. As CRRT is more expensive than IHD in the ICU,
the issue of downstream costs—obviously affected by the
need for chronic dialysis—is crucial in order to determine
which modality is more economically efficient [13]. The
aim of the present study was to assess the impact on
renal recovery of (1) the ICU choice of CRRT or IHD
and (2) comorbidities. We also studied mortality of the
cohort, consisting of Swedish patients with ARF requiring
renal replacement therapy in the ICU between 1995 and
2004.
Materials and methods
This study was approved by the Ethics Committee at the
Karolinska Institutet, Stockholm, Sweden.
Definition o f study cohort
Nationwide data on adult general ICU patients with ARF
requiring RRT were put into a database. All adult general
ICUs in Sweden were contacted, but some did not have the
means to report the required data, whereas other ICUs did
have data, but not for the entire period. In total, 32 ICUs
provided complete information regarding the subject’s
unique 10-digit national registration number, admission
date to the ICU, date of start of RRT and modality chosen
(IHD or CRRT). A total of 2,642 subjects treated between
1995 and 2004 in 32 ICUs were thus included in the
study. The date of first recorded ICU admission marked
entry into the cohort. The hospitals were classified into
three subtypes based upon size and infrastructure accord-
ing to the National Board of Health and Welfare [14].
Type 1 hospitals are regional/university hospitals, type 2
represents county hospitals and type 3 consists of local
hospitals. Regional/university hospitals have larger catch-
ment areas, and are also referral centres for type 2 and 3
hospitals.
The Swedish in-patient register and the population register
Since 1965, the National Board of Health and Welfare
has collected data on individual hospital discharges in
the in-patient register, described in detail elsewhere [15].
The proportion of the Swedish population covered by this
register increased from 60% in 1969 to 85% in 1983, and
was 100% by 1987 onwards. The population register is
run by Statistics Sweden, which rapidly and continuously
records the vital status and addresses of all Swedish citi-
zens and permanent residents.
The Swedish Register for Active Treatment of Uraemia
The Swedish Register for Active Treatment of Uraemia
(SRAU) was started in 1991 at a time when there was
a lack of reliable data on dialysis and transplantation
care in Sweden. The register includes each individual
starting active treatment of uraemia with dialysis or
kidney transplantation due to chronic renal disease. Every
change in treatment (haemodialysis, peritoneal dialysis
and transplantation) is reported. Patients are entered into
the SRAU only if their need for dialysis is permanent.
Date of first treatment marks entry, and discontinuation of
treatment leads to removal from the register [16].
Follow-up
The unique 10-digit national registration number as-
signed to every Swedish citizen ensures identification and
follow-up of the patients who have undergone RRT in
the ICU [17]. By using the registration number we could
link the individual ICU patient data with the in-patient
register, the population register and the SRAU. In this
study, the in-patient register was used for three reasons:
(1) To determine comorbidities recorded during hospital
stay present in the cohort, such as diabetes and heart
failure. (2) To record the main diagnoses during the ICU
stay, i.e. as the patients entered the cohort. (3) Patients
that were not found in the in-patient register during the
time they were reported to have been in the ICU were
excluded from the study. The population register allowed
us to record mortality of the cohort. The SRAU provided
information on patients with chronic renal disease prior
to their ICU stay. These patients were also excluded. The
validity of the in-patient registry is high, and it is used for
reimbursement, giving the hospitals an economic incentive
to be accurate [15, 18].
Furthermore, the SRAU allowed us to find the surviv-
ing patients that developed a need for chronic RRT after
ARF requiring RRT in the ICU. As only patients with per-
manent end-stage renal disease are registered in the SRAU,
for analysis of renal outcome we included only patients
found in the register that remained alive for at least 90
days. A study among all patients who had died with renal
disease since 1991 showed that less than 5% of patients
starting treatment for chronic renal failure had not been re-
ported to the SRAU [16].
Statistics
The prevalence o f permanent renal failure 90 days after
initial dialysis was analysed by logistic regression, with
covariates categorised as in Table 1. All variables except
main diagnosis at ICU were included as covariates.
Adjustment for main diagnosis at ICU was accommodated
by conditioning. Results are presented as odds ratios with
95% confidence intervals (CI). The risk of late develop-
ment of renal failure was analysed by Cox regression.
Resulting hazard ratios (HR) are presented with 95%
CI. Cumulative incidence of permanent renal failure was
estimated using a macro p rovided by Anderson [19].
The effect of dialysis mode in the ICU and subsequent
ESRD on mortality was analysed by a Cox regression
model, with recruitment to the ESRD group after 90 days
as a time-dependent variable. The risk estimates were
adjusted for p atient characteristics, calendar time and
hospital type. Survival curves were estimated through
the baseline cumulative hazard function adjusted by Cox
regression to the average value for patient characteristics,
calendar time and hospital type.
All analyses were p erformed using the Statistical Anal-
ysis System (SAS
®
) package [20].
Whole cohort Survived 90 days
CRRT IHD CRRT IHD
Characteristics N (%) n (%) n (%) n (%) n (%)
Age at entry (years)
< 40 214 (9.7) 193 (10.1) 21 (7.2) 146 (15.5) 15 (9.5)
40–49 202 (9.2) 174 (9.1) 28 (9.6) 110 (11.7) 17 (10.7)
50–59 380 (17.2) 328 (17.2) 52 (17.9) 172 (18.2) 34 (21.5)
60–69 559 (25.4) 489 (25.6) 70 (24.1) 255 (27.0) 40 (25.3)
70–79 667 (30.3) 575 (30.1) 92 (31.6) 207 (21.9) 37 (23.4)
80+ 180 (8.2) 152 (8.0) 28 (9.6) 54 (5.7) 15 (9.5)
Sex
Female 740 (33.6) 657 (34.4) 83 (28.5) 333 (35.3) 49 (31.0)
Male 1462 (66.4) 1254 (65.6) 208 (71.5) 611 (64.7) 109 (69.0)
Diagnosis before admission
Diabetes 355 (16.1) 312 (16.3) 43 (14.8) 162 (17.1) 22 (13.9)
No diabetes 1847 (83.9) 1599 (83.7) 248 (85.2) 782 (82.8) 136 (86.1)
Heart failure 356 (16.1) 315 (16.5) 41 (14.1) 111 (11.8) 9 (5.7)
No heart failure 1846 (83.9) 1596 (83.5) 250 (85.9) 833 (88.2) 146 (94.3)
Main ICU diagnosis
AAA repair 272 (12.4) 235 (12.3) 37 (12.7) 91 (9.6) 23 (14.6)
Cancer 195 (8.9) 170 (8.9) 25 (8.6) 48 (5.1) 6 (3.8)
GI incl. pancreatitis 281 (12.8) 253 (13.2) 28 (9.6) 123 (13.0) 11 (6.7)
Intoxication 71 (3.2) 44 (2.3) 27 (9.3) 39 (4.1) 21 (13.3)
Cardiovascular 207 (9.4) 171 (9.0) 36 (12.4) 80 (8.5) 14 (8.9)
T rauma 155 (7.0) 139 (7.3) 16 (5.5) 84 (8.9) 10 (6.3)
Sepsis 355 (16.1) 325 (17.0) 30 (10.3) 166 (17.6) 16 (10.1)
Other diagnoses 666 (30.2) 574 (30.0) 92 (31.6) 313 (33.2) 57 (36.1)
Total 2202 (100) 1911 (86.8) 291 (13.2) 1911 (86.8) 291 (13.2)
Table 1 Baseline characteristics
among the 2,202 subjects treated
with RRT at the ICU
Results
In total, 2,642 patients from 32 ICUs were reported to have
been treated with RRT between 1995 and 2004. Patients
lacking information o n main diagnosis (n = 188) in the
in-patient register during their reported ICU admission
were excluded. Moreover, 252 were dialysis-dependent
prior to their treatment in the ICU and were excluded,
leaving 2,202 for final analysis (Fig. 1). In only 3 7 patients
was there a switch in treatment from CRRT to IHD, while
no patients crossed over from IHD to CRRT.
There were no differences between IHD and CRRT pa-
tients regarding baseline characteristics, such as age, sex
and comorbidities (Table 1). The main ICU diagnoses were
evenly distributed, but sepsis was commonly treated with
CRRT and intoxication with IHD. CRRT was more com-
mon in type 1 and 2 hospitals. A transition towards CRRT
was observed over time (Table 2).
Mortality
A total of 1,102 patients survived and 1,100 patients died
within 90 days. The use of IHD or CRRT did not have
Fig. 1 Flowchart of exclusion criteria and outcome of the cohort
Table 2 Ninety-day mortality among the 2,202 subjects treated with
RRT at the ICU
Hospital type
Type of RRT I II III
CRRT 952 (92.2) 861 (81.3) 98 (88.2)
IHD 80 (7.8) 198 (18.7) 13 (11.7)
Total 1032 (100%) 1059 (100%) 111 (100%)
Period
1995–1999 2000–2004
CRRT 447 (76.0) 1464 (90.7)
IHD 141 (24.0) 150 (9.3)
Total 588 (100%) 1614 (100%)
a significant difference on 90-day mortality (45.7% and
50.6% respectively). Neither did hospital type, where 90-
day mortality was 49.7%, 50.6% and 47.8% for type 1,
2 and 3 hospitals respectively. Unsurprisingly, age group,
heart failure, but also admittance before the year 2000 cor-
related with death at 90 days (data not shown). The impact
of main ICU diagnosis shows that cancer stands out with
the highest 90-day mortality, 72.3% (95% CI 65.5–78.5),
whereas intoxication displays the lowest mortality within
90 days, 15.5% (95% CI 8–26).
Among 90-day survivors, long-term mortality (Fig. 2)
reveals an elevated risk of death for IHD patients that
developed ESRD, with an HR of 2.29 (95% CI 1.27–4.13)
compared with CRRT patients with ESRD. In contrast,
IHD patients that did not develop ESRD had non-
significantly lower mortality than their CRRT counterparts
(HR 0.79, 95% CI 0.55–1.14).
Renal outcome
Out of the 1,102 patients surviving 90 days, 944 (85.7%)
were treated with CRRT and 158 (14.3%) with IHD.
Seventy-eight patients (8.3%, 95% CI 6.6–10.2) never
Fig. 2 Kaplan–Meier survival function, all deaths among patients by
treatment
CRRT (n = 944) IHD (n = 158)
n (%) OR n (%) OR
a
(95% CI) OR
b
(95% CI) OR
c
(95% CI)
ESRD 78 (8.3) 1.0 26 (16.5) 2.19 (1.4–3.5) 2.13 (1.3–3.5) 2.60 (1.5–4.3)
a
OR, crude
b
OR, adjusted for age, sex, diabetes or heart failure before admission and calendar year
c
OR, adjusted for age, sex, diabetes or heart failure before admission, calendar year, hospital type and
main diagnosis at ICU
Table 3 Odds ratios of renal
failure for patients treated with
IHD or CRRT among the 1,102
patients surviving 90 days after
inclusion in the cohort
Fig. 3 Cumulative incidence of permanent renal failure among pa-
tients surviving 90 days
recovered their renal function in the CRRT group. The
proportion was significantly higher among IHD patients,
where 26 subjects (16.5%, 95% CI 11.0–23.2) developed
the need for chronic dialysis. Table 3 highlights the
elevated risk for ESRD associated with IHD.
Figure 3 shows “late” development of ESRD among
the 998 patients that survived and were not found in the
SRAU during the first 90 days. Out of 866 patients on
CRRT, 31 (3.6%, 95% CI 2.4–5.0) were later found in the
SRAU, compared with 3 out of 132 IHD patients (2.3%,
95% CI 0.5–6.5). Over time, the differing risk for ESRD
diminishes between IHD and CRRT groups. The only
other variable showing an impact on the need for chronic
dialysis was diabetes prior to admission, with an HR of
4.3 (CI 2.1–9.0) after adjusting for age and sex.
Discussion
In this nationwide study we found a significantly higher
risk for chronic renal failure with dialysis dependency af-
ter critical illness for patients treated with IHD than for
patients treated with CRRT. Furthermore, patients treated
with IHD that ended up with ESRD showed the highest
mortality.
Previous attempts to determine whether the choice of
RRT affects outcome have focused on mortality. A recent
study showed that if guidelines to improve tolerance and
metabolic control were used, 60-day mortality did not dif-
fer between CRRT and IHD [21].
A meta-analysis by Kellum et al. compared CRRT with
IHD [22]. That investigation found no difference in overall
mortality. However, adjusting for study quality and sever-
ity of illness, mortality was lower with CRRT (RR 0.72,
CI 0.60–0.87, p< 0.01). These findings were criticised by
Tonelli and co-workers [23], who, in a meta-analysis of
their own, found no survival advantage in unselected criti-
cally ill patients with ARF. They did, however, find a non-
significantly higher relative risk for ESRD in IHD patients.
In the study by Mehta et al., CRRT was found to be bene-
ficial regarding renal recovery. Chronic renal insufficiency
at death or hospital discharge was diagnosed in 17% of
patients whose therapy was IHD versus only 4% of those
whose initial therapy was CRRT (p = 0.01). For patients
receiving an adequate trial of monotherapy, recovery of
renal function was 92% for CRRT versus 59% for IHD
(p< 0.01). Lastly, a higher proportion of subjects cross-
ing over from IHD to CRRT recovered their renal function
than patients crossing over in the opposite direction (45 vs.
7%, p< 0.01) [24].
A single-centre study did focus on renal recovery. In
93 patients with ARF it was found that 12.5% of CRRT
patients and 64.3% of IHD patients were dialysis depen-
dent at hospital discharge [25]. Although this investigation
showed surprisingly high numbers of IHD patients who
developed ESRD, it did use hospital discharge, whereas
earlier studies of patients treated with IHD [7, 8] used ICU
discharge as an end-point and found 30% to be dialysis
dependent. In a prospective study of renal recovery Schif
demonstrated that 33% had mild to moderate failure and
10% had severe renal failure at discharge [26]. However,
only one patient progressed to ESRD. In contrast to this,
Augustine et al. defined renal recovery as discontinuation
of dialysis therapy before discharge from the hospital,
and 64% of the survivors were thus considered to have
not recovered their renal function [27]. This randomised
controlled trial of 80 patients found renal recovery in 9
patients (36% of survivors, or 11% in total) and noted
no difference between IHD and CRRT. It is possible
that use of both ICU discharge and hospital discharge
as cut-off point could lead to an overestimation of the
number of subjects needing chronic dialysis. In the p resent
study we define chronic renal failure as a p ersisting need
for dialysis for over 3 months. Linkage to the SRAU
enabled us to identify all patients developing the need
for chronic dialysis up to 10 years after ICU a dmission.
One could argue that the patients registered in the SRAU
later than 90 days after their ICU discharge did not
develop kidney failure as a direct result of their ARF
requiring treatment in the ICU. For instance, one study
followed the patients for 6 months after ICU discharge,
but later need for chronic RRT was not considered [3].
However, we believe that long-term renal morbidity must
be regarded as a potential result of the acute kidney
injury.
The biological hypothesisthat IHD could aggravate the
kidney injury in ARF—is based on several observations.
The use of IHD in critically ill patients could lead to an
increase in oxygen consumption [28] and a reduction in
cardiac index in the first hour of IHD [29]. Davenport and
co-workers [29] also report reductions in mean arterial
pressure, pulmona ry capillary wedge pressure and tissue
oxygen uptake. IHD is associated with haemodynamic
instability during dialysis [30–32]. With CRRT, volume
control is continuous, and avoidance of the intravascular
volume depletion and hypotension may prevent treatment-
associated ischaemic renal injury reported during standard
IHD [12].
Renal recovery is an important measure of outcome
for many reasons. First, chronic dialysis therapy is associ-
ated with significant impairment of health-related quality
of life [33–36]. Secondly, it is costly; with annual costs in
the range of $51,252–$69,517 [37, 38]. One study showed
that the estimated cost per quality-adjusted life-year saved
by initiating dialysis was $128,200 [39]. Lastly, the overall
mortality of patients with renal failure requiring dialysis
exceeds that of the general population. Recent SRAU data
report a 27.4% yearly mortality ratio [40].
The limitations of this study needs to be evaluated.
We do not have ICU data on these patients, such as
RIFLE, APACHE II or SOFA scores, time on ventilator
and need for inotropic support. Even though we have
type 1, 2 and 3 hospitals, the specific ICU organisation is
unknown (availability of intensivists, whether intensivists
or nephrologists initiate and execute RRT). Moreover,
we lack information regarding dialysis dose and time on
dialysis. The risk of residual confounding by time period
must also be considered: from 2000 to 2004, 90.7% of all
patients were treated with CRRT, compared with 76% in
the earlier period. Thus, 48% of the IHD patients were
treated during the earlier period, compared with only
23% in the CRRT group. However, the fact that the risk
estimates were larger than 2 after adjusting for time period
indicates that this cannot be explained solely by residual
confounding.
Given the lack of suitable data on severity of illness,
the assumption that the patients treated with IHD and
CRRT are similar is therefore based on pre-ICU comor-
bidity information, age, sex and main diagnosis during
the ICU stay. Studying the aforementioned data, it does,
however, seem likely that the RRT choice was independent
of patient status. If anything, the information we do have
shows that sicker patients were more often than not treated
with CRRT. This is illustrated by the fact that patients on
CRRT had more diabetes and heart failure prior to their
ICU episode. Also, patients with sepsis and pancreatitis
were frequently treated with CRRT. In contrast, the
condition with the lowest mortality, intoxication, was
often treated with IHD. Some data in this study, including
the lack of cross-over, point to the fact that the RRT
modality chosen was largely dependent on the type of
equipment available at the hospital. Underlying renal
disease is probably a predictor of renal recovery. Lack
of data regarding this is problematic, but again, nothing
in this study indicates that those with underlying disease
(acute on chronic) would have been more likely to have
been treated with IHD. As mentioned, diabetic patients
(with an elevated risk of ESRD) were more often than not
treated with CRRT.
A close scrutiny of the difference in renal morbidity
between patients treated with IHD or CRRT and the
temporal difference in recruitment to chronic renal failure
between the two modalities—arouses questions (Fig. 3).
Without claiming to have a biological answer to the data
in this study, we speculate on the impact of the treatment
chosen. Seemingly, IHD has a greater impact on renal
function than CRRT which is shown as manifest renal
failure developing faster. In contrast, CRRT leads to
a smaller imminent need for chronic RRT, but over the
years we note an increasing number of patients in the
CRRT group ending up with ESRD, and after 10 years
the total risk for ESRD is c lose to that of the IHD group.
The assumption that the modality used has a physiologic
impact is strengthened by the higher mortality seen in the
IHD patients that do develop ESRD.
Conclusions
This large cohort study of intensive care patients with
ARF requiring RRT retrospectively studied the outcome in
terms of morbidity and mortality. We found that patients
ending up in need of long-term dialysis for ESRD more
often had been treated with IHD than with CRRT. The
higher risk for chronic renal failure with life-long dialysis
dependency for patients treated with IHD might lead
to a global re-evaluation of which technique should be
recommended for critically ill patients.
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... The current evidence and KDIGO guideline support the implementation of CRRT in hemodynamically unstable patients and those with increased intracranial pressure [7]. Moreover, there is increasing evidence that CRRT is associated with a trend of short-and longterm dialysis independence [8][9][10][11]. However, there is no evidence demonstrating a mortality difference between all these modalities of RRT [8,10]. ...
... Moreover, there is increasing evidence that CRRT is associated with a trend of short-and longterm dialysis independence [8][9][10][11]. However, there is no evidence demonstrating a mortality difference between all these modalities of RRT [8,10]. The KDIGO guideline recommends the use of CRRT and IHD as complementary therapies in AKI patients [7]. ...
... This is due to its ability to provide accurate volume control, slow correction of metabolic abnormalities, and hemodynamic stability [7,56,57]. In addition, CRRT has been shown to be associated with lower rate of dialysis dependence than intermittent hemodialysis [8][9][10][11]. ...
... Further, in a cohort study of 9425 patients with postoperative AKI, patients with pre-existing kidney disease had higher risks of long-term mortality and dialysis dependency than those without preexisting kidney disease [32]. Additionally, in several studies, the CRRT group showed better renal recovery and lower rate of dialysis dependency than the dialysis group [24,[33][34][35][36]. Similarly, our results showed that the cumulative incidence of ESKD was higher in the dialysis group than in the CRRT group, especially in the subgroup with pre-existing kidney disease. ...
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Article
The outcomes depending on the type of renal replacement therapy (RRT) or pre-existing kidney disease in critically ill patients with acute kidney injury (AKI) have not been fully elucidated. All adult intensive care unit patients with AKI in Korea from 2008 to 2015 were screened. A total of 124,182 patients, including 21,165 patients with pre-existing kidney disease, were divided into three groups: control (no RRT), dialysis, and continuous RRT (CRRT). In-hospital mortality and progression to end-stage kidney disease (ESKD) were analyzed according to the presence of pre-existing kidney disease. The CRRT group had a higher risk of in-hospital mortality. Among the patients with pre-existing kidney disease, the dialysis group had a lower risk of in-hospital mortality compared to other groups. The risk of ESKD was higher in the dialysis and CRRT groups compared to the control group. In the CRRT group, the risk of ESKD was even higher in patients without pre-existing kidney disease. Although both dialysis and CRRT groups showed a higher incidence of ESKD, in-hospital mortality was lower in the dialysis group, especially in patients with pre-existing kidney disease. Our study supports that RRT and pre-existing kidney disease may be important prognostic factors for overall and renal outcomes in patients with AKI.
... Some large observational studies, that only included patients who were receiving RRT, suggest that CRRT is an independent predictor of renal recovery among survivors [23,24]. CRRT could permit slow but continuous removal of solutes and water, thereby conferring better hemodynamic tolerability. ...
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Article
Background Critically ill patients with severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) have a grim prognosis. Recently, multiple studies focused on the impact of KRT initiation time (i.e., accelerated vs. watchful waiting KRT initiation [WWS-KRT]) on patient outcomes. We aim to review the results of all related clinical trials. Methods In this systematic review, we searched all relevant randomized clinical trials from January 2000 to April 2021. We assessed the impacts of accelerated vs. WWS-KRT on KRT-dependence, KRT-free days, mortality, and adverse events, including hypotension and infection arrhythmia and bleeding. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. Results A total of 4,932 critically ill patients with AKI from 10 randomized clinical trials were included in this analysis. The overall 28-day mortality rate was 38.5%. The 28-day KRT-dependence rate was 13.0%. The overall incident of KRT in the accelerated group was 97.4%, and 62.8% in the WWS-KRT group. KRT in the accelerated group started 36.7 hours earlier than the WWS-KRT group. The two groups had similar risks of 28-day [pooled log odds ratio (OR): 1.001, p = 0.982] and 90-day (OR: 0.999, p = 0.991) mortality rates. The accelerated group had a significantly higher risk of 90-day KRT dependence (OR: 1.589, p = 0.007), hypotension (OR:1.687, p<0.001), and infection (OR:1.38, p = 0.04) compared with the WWS-KRT group. Conclusions This meta-analysis revealed that accelerated KRT leads to a higher probability of 90-day KRT dependence and dialysis-related complications without any impact on mortality rate when compared with WWS-KRT. Therefore, we suggest the WWS-KRT strategy for critically ill patients.
... [11,12] There is some evidence emerging that there may be greater long-term freedom from RRT in CRRT as compared with SLED/IHD. [13,14] In our setting, access to CRRT is limited by the availability of machines capable of this technique and the availability of trained staff to operate these machines. Therefore, the use of IHD/ SLED is appropriate. ...
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Article
Background: Renal replacement therapy (RRT) is a scarce resource in southern Africa. Critically ill patients are at risk of developing acute kidney injury (AKI), which may require RRT. There are few data on the utilisation of RRT in southern African intensive care units (ICUs). Objectives: To determine the indications for initiating RRT in critically ill patients in ICUs in KwaZulu-Natal, South Africa (SA) and to describe the methods and dosing of RRT. Methods: A prospective observational study was performed to investigate the indications for initiating, methods and dosing of RRT among patients admitted to four ICUs in KwaZulu-Natal Province, SA. All adult patients were eligible for inclusion. Results: A total of 108 patients who received RRT were included in the study. The most common reasons for initiation of RRT were a high/rising creatinine, high/rising urea, acidosis and fluid balance. The majority of the patients (79.6%; n=86) had three or more indications for RRT. A total of 353 intermittent haemodialysis/slow low-efficiency dialysis (IHD/SLED) sessions and 84 continuous renal replacement therapy (CRRT) sessions were recorded. The median (interquartile range (IQR)) CRRT dose was 25.8 (19.1 - 28.8) mL/kg/h. The median (IQR) urea reduction ratio for IHD/SLED was 32.4% (15.0 - 49.8). Conclusion: Patients in this study had multiple indications for initiating RRT. The dosing of RRT was not optimal, with a wide range shown in CRRT, and the majority of patients did not achieve a urea reduction ratio (URR) >65%. Contributions of the study: Renal replacement therapy is a scarce resource in Africa. Little is known about the current types and dosing of RRT in critical care units in South Africa. We showed that critically ill patients had multiple indications for RRT and the dosing was not optimal.
... Studies examining the outcome of AKI-D showed different outcomes based on the dialysis modality used. CKRT is considered by some to be superior to intermittent hemodialysis (IHD) in managing AKI-D [3,[76][77][78][79], as this modality causes less intradialytic hypotension and may provide better control of fluid balance and more hemodynamic stabilization [80]. Conger and Schrier were among the earliest scientist to study the association between the changes in systemic and renal hemodynamics and AKI. ...
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Article
Acute kidney injury (AKI) is a common clinical syndrome characterized by rapid impairment of kidney function. The incidence of AKI and its severe form AKI requiring dialysis (AKI-D) has been increasing over the years. AKI etiology may be multifactorial and is substantially associated with increased morbidity and mortality. The outcome of AKI-D can vary from partial or complete recovery to transitioning to chronic kidney disease, end stage kidney disease, or even death. Predicting outcomes of patients with AKI is crucial as it may allow clinicians to guide policy regarding adequate management of this problem and offer the best long-term options to their patients in advance. In this manuscript, we will review the current evidence regarding the determinants of AKI outcomes, focusing on AKI-D.
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Objective We retrospectively analyzed risk factors on in-hospital mortality in CRRT-therapy patients with open cardiac surgery (CS)-induced acute kidney injury (AKI), to provide the clinical basis for predicting and lowering the in-hospital mortality after CS. Methods 84 CS-AKI patients with CRRT were divided into survival and death groups according to discharge status, and the perioperative data were analyzed with R version 4.0.2. Results There were significant differences between the two groups, including: urea nitrogen, Sequential Organ Failure Assessment (SOFA) score and vasoactive-inotropic score (VIS) on the first day after operation; VIS just before CRRT; SOFA score and negative balance of blood volume 24 h after CRRT; the incidence rate of bleeding, severe infection and MODS after operation; and the interval between AKI and CRRT. Univariate logistic regression analysis showed that SOFA score and VIS on the first day after operation; VIS just before CRRT; VIS and negative balance of blood volume 24 h after CRRT; the incidence rate of bleeding, infection and multiple organ dysfunction syndrome (MODS) after operation; bootstrap resampling analysis showed that SOFA score and VIS 24 h after CRRT, as well as the incidence of bleeding after operation were the independent risk factors. Conclusion Maintaining stable hemodynamics and active prevention of bleeding are expected to decrease the in-hospital mortality.
Article
Background: Acute kidney injury (AKI) is commonly seen in the PICU and is associated with poor short-term and long-term outcomes, especially in patients who required continuous kidney replacement therapy (CKRT). However, as the trajectory of kidney recovery in these patients remain uncertain, determination of the timing to convert to permanent kidney replacement therapy (KRT) remains a major challenge. We aimed to examine the frequency and timing of kidney recovery in pediatric AKI survivors that required CKRT. Methods: We performed a retrospective study of patients under 18 years old who received CKRT for AKI in a tertiary-care PICU over 6 years. Primary outcomes were the rate of KRT withdrawal due to kidney recovery and KRT-dependent days for those who survived to hospital discharge. Secondary outcomes were all-cause mortality, dialysis dependence, and occurrences of estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 and eGFR < 60 mL/min/1.73m2 one year after initiation of the index CKRT in survivors. Results: Thirty-nine patients were included. Of the 28 children who survived to hospital discharge, 26 (93%) withdrew from dialysis due to kidney recovery, all within 30 days. Twenty-three patients were followed up. One had died, five had an eGFR of 60 mL/min/1.73m2 or more but less than 90 mL/min/1.73m2, and two had an eGFR < 60 mL/min/1.73m2, of which one required peritoneal dialysis. Conclusions: Over 90% of the survivors withdrew CKRT within 30 days. However, the frequency of abnormal eGFR one year after initiation of CKRT in survivors exceeded 30% and supports the recommendation of post-AKI follow-up.
Article
Background: The frequency of acute kidney injury (AKI) can be as high as 50% in the intensive care unit (ICU). Despite the publication of national guidelines in France in 2015 for the use of RRT, there are no data describing the implementation of these recommendations in real-life. Methods: We performed a nationwide survey of practices from November 15, 2019, to January 24, 2020, in France. An electronic questionnaire based on the items recommended in the national guidelines was sent using an online survey platform, to the chiefs of all ICUs in France. The questionnaire comprised a section for the Department Chief about local organization and facilities, and a second section destined for individual physicians about their personal practices. Results: We contacted the Department Chief in 356 eligible ICUs, of whom 88 (24.7%) responded regarding their ICU organization. From these 88 ICUs, 232/285 physicians (82%) completed the questionnaire regarding individual practices. The practices reported by respondent physicians were as follows: intermittent RRT was first-line choice in >75% in a patient with single organ (kidney) failure at the acute phase, whereas continuous RRT was predominant (>75%) in patients with septic shock or multi-organ failure. Blood and dialysate flow for intermittent RRT were 200-300 mL/min and 400-600 mL/min, respectively. The dose of dialysis for continuous RRT was 25-35 mL/kg/h (65%). Insertion of the dialysis catheter was mainly performed by the resident under echographic guidance, in the right internal jugular vein. The most commonly used catheter lock was citrate (53%). The most frequently cited criterion for weaning from RRT was diuresis, followed by a drop in urinary markers (urea and creatinine). Conclusion: This study shows a satisfactory level of reported compliance with French guidelines and recent scientific evidence among ICU physicians regarding initiation of RRT for AKI in the ICU.
Article
Expanded use and steady improvements in continuous renal replacement techniques (CRRT) have enhanced the safety of the application of kidney replacement therapy (KRT) to hemodynamically unstable intensive care unit (ICU) patients. The longer duration of therapy and the personalized prescription provided by continuous therapies are associated with greater hemodynamic stability and a modestly higher likelihood of kidney recovery than standard intermittent hemodialysis (IHD). Studies designed to evaluate the effect on mortality over intermittent therapies lack evidence of benefit. A lack of standardization and considerable variation in how CRRT is performed leads to wide variation in how the technique is prescribed, delivered, and optimized. Technology has progressed in critical care nephrology, and more progress is coming. New CRRT machines are equipped with a friendly user interface that allows easy performance and monitoring, permitting outcome measurements and improved patient quality control. This review discusses the key concepts necessary to guide nephrologists to prescribe and deliver KRT to critically ill ICU patients.
Chapter
Acute kidney injury (AKI) remains a frequent and serious complication of surgical procedures and critical illness that is consistently associated with worse outcomes and increased long-term morbidity and mortality. Much work has gone into finding kidney protective measures with disappointingly few therapeutic options available to prevent or to treat AKI. Research has defined some effective kidney protective practices and the purpose of this chapter is to help the clinician to differentiate better clinical practices that are either ineffective, detrimental, or protective to the kidney. The chapter will first provide an introduction to kidney physiology with particular focus on areas that make it vulnerable to injury. The chapter will then shift focus to diagnosis of kidney injury including definitions and early biomarkers that can help risk stratify patients. Then, specific mechanisms of postoperative and critical illness-associated kidney injury will be outlined. The rest of the chapter will review evidence from renal-protective research studies pertinent to the preoperative, intraoperative, and postoperative periods. After reading this chapter, the clinician should have a more robust framework for adoption (mostly avoidance) of renal protective practices (stratified based on level of evidence available) to guide their clinical practice.
Article
Background: Renal failure requiring dialysis in the setting of hospitalization for serious illness is a poor prognostic sign, and dialysis and aggressive care are sometimes withheld. Objective: To evaluate the clinical outcomes and cost-effectiveness of initiating dialysis and continuing aggressive care for seriously ill hospitalized patients. Design: Prospective cohort study and cost-effectiveness analysis. Setting: Five geographically diverse teaching hospitals. Patients: 490 patients (median age, 61 years; 58% women) enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) in whom dialysis was initiated. Measurements: Survival, functional status, quality of life, and health care costs. Life expectancy was estimated by extrapolating survival data (up to 4.4 years of follow-up) using a declining exponential function. Utilities (quality-of-life weights) were estimated by using time-tradeoff questions. Costs were based on data from SUPPORT and published Medicare data. Results: Median duration of survival was 32 days, and only 27% of patients were alive after 6 months. Survivors reported a median of one dependency in activities of daily living, and 62% rated their quality of life as good or better. Overall, the estimated cost per quality-adjusted life-year saved by initiating dialysis and continuing aggressive care rather than withholding dialysis and allowing death to occur was $128 200. For the 103 patients in the worst prognostic category, the estimated cost per quality-adjusted life-year was $274 100; for the 94 patients in the best prognostic category, the cost per quality-adjusted life-year was $61 900. Conclusions: For the few patients who survived, clinical outcomes were fairly good. With the exception of patients with the best prognoses, however, the cost-effectiveness of initiating dialysis and continuing aggressive care far exceeded S50 000 per quality-adjusted life-year, a commonly cited threshold for cost-effective care.
Article
Background: Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill persons with acute renal failure is distressingly high. Previous efforts to predict outcome in this population have been limited by small sample size and the absence of uniform exclusion criteria. Additionally, data obtained decades ago may not apply today owing to changes in case mix.Methods: The medical records of 132 consecutive patients in the intensive care unit with acute renal failure who required dialysis from 1991 through 1993 were evaluated by a blinded reviewer.Results: The overall in-hospital mortality rate was 70%. Twelve readily available historical, clinical, and laboratory variables were significantly associated with in-hospital mortality. Multivariate logistic regression analysis showed that mechanical ventilation, malignancy, and nonrespiratory organ system failure were independently associated with in-hospital mortality. Using a 95% positivity criterion, this model identified 24% of high-risk patients who died, without misclassification of any survivors. Of those who survived to hospital discharge, 33% were dialysis dependent and 28% were institutionalized long-term.Conclusions: Among critically ill patients, acute renal failure requiring dialysis is an ominous condition with a high risk of in-hospital mortality. This risk appears to depend largely on comorbid conditions, such as the need for mechanical ventilation and underlying malignancy. While this prognostic model requires prospective validation, it appears to identify a substantial fraction of patients for whom dialysis may be of limited or no benefit.(Arch Intern Med. 1995;155:1505-1511)
Article
Epidemiology of acute renal failure (ARF): A prospective, multicenter, community-based study. There are very limited data on overall epidemiology of ARF. It is crucial to know the incidence, etiology and clinical features of ARF to promote prevention strategies and to implement adequate resources for the management of this entity. During a nine month period, a collaborative prospective protocol with 98 variables was developed to assess all ARF episodes encountered in the 13 tertiary-care hospitals in Madrid, Spain (covering 4.2 million people of over 14 years of age). ARF was considered when a sudden rise in serum creatinine concentration (SCr) to more than 177 µmol/liter was found in patients with normal renal function, or when the sudden rise (50% or more) was observed in patients with previous mild-to-moderate chronic renal failure (SCr < 264 µmol/liter). Of the 748 cases of ARF studied, 665 episodes presented in inhabitans from the Madrid area. This gives an overall incidence of ARF of 209 cases per million population (p.m.p.; 95% CI 195 to 223). The incidence of acute tubular necrosis (ATN) was 88 cases p.m.p. (95% CI 79 to 97), prerenal ARF 46 p.m.p (95% CI 40 to 52), acute-onset chronic ARF 29 p.m.p. (95% CI 24 to 34), and obstructive ARF 23 p.m.p. (95% CI 19 to 27). The mean age was 63 ± 17 years. The most frequent causes of ARF were ATN (45%), prerenal (21%), acute-onset chronic renal failure (12.7%) and obstructive ARF (10%). Renal function was normal at admission in 48% of patients who later developed ARF. Mortality (45%) was much higher than that of the other patients admitted (5.4%, P < 0.001). This real outcome correlated extremely well with the expected outcome calculated through out the severity index of ARF (SI) 0.433 ± 0.246 (mean ± SD). In 187 cases, mortality was attributed to underlying disease, thus corrected mortality due to ARF was 26.7%. Dialysis was required in 36% of patients, and was associated with a significantly higher SI of ARF (0.57 ± 0.23 vs. 0.35 ± 0.19, P < 0.001) and mortality (65.9 vs. 33.2%, P < 0.001). Mortality in patients hemodialyzed with biocompatible synthetic membranes (N = 50) was similar to that observed with cellulosic ones (N = 84; 66% vs. 59.5%, NS). Mortality was higher in patients with coma, assisted respiration, hypotension, jaundice (all P < 0.001) and oliguria (P < 0.02). This study gives, for the first time, the incidence of all forms of ARF in a developed country. ARF is iatrogenically incuced at a high rate by modern medicine. Prevention strategies, Particularly in the perioperative period, are needed to decrease its impact.
Article
To determine the mechanism of observed differences in vasoreactivity in norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure (ARF), induction renal blood flow (RBF) was measured and vascular reactivity examined one week thereafter in NE- and RAC-ARF rat kidneys that had identical levels of renal dysfunction. Morphology also was compared at 48 hours and one week. In NE-ARF, RBF was 14% during 90 minutes of induction and by 60 minutes post-NE infusion was only 18% of baseline. In contrast, in RAC-ARF RBF was effectively 0 for 75 minutes but returned to 95% of baseline by 60 minutes after clamp release. At one week there was a paradoxical increase in renovascular resistance (RVR) to renal perfusion pressure (RPP) reduction in the autoregulatory range and an augmented vasoconstriction to renal nerve stimulation (RNS) in NE-ARF, but no change in RVR and minimal reduction in RBF to these same respective stimuli in RAC-ARF (both different at P less than 0.001). NE-ARF were more sensitive to intrarenal norepinephrine than RAC-ARF kidneys (P less than 0.001). Neither NE- nor RAC-ARF kidneys responded to endothelium-dependent acetylcholine (ACh). Vasodilation to endothelium-independent prostacyclin (PGI2) in NE- was similar to sham-ARF, but there was an attenuated response in RAC-ARF kidneys (P less than 0.001). Morphology at 48 hours showed smooth muscle necrosis in half of the resistance vessels in RAC- but in less than 10% of those in NE-ARF. Except for a slightly greater frequency of tubular casts at 48 hours in RAC-ARF, tubular injury was indistinguishable. It is concluded that NE-ARF has evidence of a predominant functional endothelial vascular injury while RAC-ARF has both morphologic and functional evidence of a predominant smooth muscle injury. Differences in vascular injury between the two models, at least in part, may be the consequence of differences in severity of initial ischemia and/or the rates of recovery of RBF; however, an additional or separate toxic effect of infused NE cannot be excluded.
Article
The quality of life of patients with end-stage renal disease was estimated using the time trade-off technique. The sample included 103 transplant, 60 hospital hemodialysis, 57 home/self-care, and 52 continuous ambulatory peritoneal dialysis patients. Test-retest reliability was high: intra-class correlation coefficient 0.81 (p less than 0.001). The correlations of the time trade-off with the Spitzer Quality of Life index and a visual analogue scale completed by the nephrologists, nurses, friends/relatives, and the patient were positive and statistically significant, but still relatively low (r = 0.22-0.43; p less than 0.01). The time trade-off demonstrated evidence for discriminative construct validity by ordering treatment groups according to a priori prediction. The mean time trade-off values and standard deviations (where death is 0 and full health is 1) were 0.43 (0.26) for hospital hemodialysis 0.49 (0.23) for home/self-care hemodialysis, 0.56 (0.29) for continuous ambulatory peritoneal dialysis, and 0.84 (0.24) for transplant. Analysis of variance showed transplant to be different from all other groups (p less than 0.001) with age, sex, time with end-stage renal disease, and work status making no significant independent contribution. The partial correlation coefficients between time trade-off score and items in the physical, social, and emotional functioning sub-scales of the Rand questionnaire showed that physical functioning was far more important than social or emotional functioning. The time trade-off is reliable, demonstrates evidence for validity, and suggests that the quality of life for patients with end-stage renal disease is much poorer than that reported previously.
Article
The effect of hemorrhagic reduction in systemic blood pressure (SBP) to 90 mm Hg for four hours on autoregulation of renal blood flow (RBF), renal function, and renal histology was examined in control rats, one week norepinephrine-induced acute renal failure (NE-ARF) rats with intact renal nerves, and one week NE-ARF rats with prior renal denervation. The results showed that in control rats, hemorrhagic SBP reduction to 90 mm Hg had no effect on autoregulation of RBF (autoregulatory index = 0.09 +/- 0.02), creatinine clearance, or renal histology. However, in one week NE-ARF rats with intact renal nerves, hemorrhagic reduction in SBP to 90 mm Hg was associated with marked impairment of autoregulation of RBF (autoregulatory index = 3.49 +/- 0.25), further reduction in creatinine clearance from 0.59 +/- 0.08 ml/min to 0.36 +/- 0.14 ml/min, and histologic evidence of recurrent ischemic injury. Renal denervation prior to SBP reduction improved autoregulation of RBF (autoregulatory index = 0.30 +/- 0.09), prevented the further reduction in creatinine clearance, and significantly ameliorated the deleterious effect on renal histology seen in innervated NE-ARF rats. These results suggest the potential importance of the loss of autoregulation of RBF on the course of NE-ARF, and further support the pathogenetic role of renal nerves in the loss of autoregulation.