The effect of sustained low efficient dialysis versus continuous renal replacement

therapy on renal recovery after acute kidney injury in the intensive care unit:

A systematic review and meta-analysis

Bernadett Kovacs1, Katrina J. Sullivan2, Swapnil Hiremath2,3,4, Rakesh V. Patel2,3,5

1
Montfort Hospital, Department of Medicine, 713 Montreal Road, Ottawa, ON, K1K 0T2
2
The Ottawa Hospital Research Institute, 501 Smyth Rd, Ottawa, ON, K1H 8L6
3
Department of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON, K1H 8M5
4
Division of Nephrology, The Ottawa Hospital, 501 Smyth Rd, Ottawa, ON, K1H 8L6
5
Department of Critical Care, The Ottawa Hospital, Box 207, 501 Smyth Rd, Ottawa, ON,

K1H 8L6

Corresponding author:

Rakesh V. Patel M.D.

Box 207, Department of Critical Care

The Ottawa Hospital, General Campus

501 Smyth Rd, Ottawa, ON Canada K1H 8L6

rpatel@ohri.ca

613-737-8899 x79830

Fax: 613-739-6695

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/nep.13009

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Abstract:

Aim: Acute kidney injury (AKI) is a significant contributing factor to the morbidity and

mortality of critically ill adults, yet there remains controversy on the optimal renal

replacement therapy mode for these patients. The aim of our systematic review was to

determine the effect of sustained low-efficiency dialysis or continuous renal replacement

therapy on patient outcomes in critically ill patients with AKI.

Methods: A systematic search of Medline, Embase, CINAHL, and the Cochrane Library was

conducted in February 2015. Identified citations were screened independently in duplicate

and the methodological quality of included studies was evaluated. Data were extracted on

study, patient, and intervention characteristics, as well as clinical outcomes. Results were

pooled using inverse variance fixed and random effects meta-analysis.

Results: A total of 1564 patients in 18 studies were included. Meta-analysis indicated no

statistically significant difference in our primary outcome, overall renal recovery (risk ratio

(RR) 0.87, 95% confidence interval (CI) 0.63-1.20, I2 66%). No significant difference was

observed for the secondary outcome of time to renal recovery (mean difference 1.33, 95% CI

0.23-2.88, I2 0%). SLED was slightly favoured over CRRT in statistically significant manner

for the secondary outcome of mortality (RR 1.21, 95% CI 1.02-1.43, I2 47%), however this

diminished when sensitivity analysis of only RCTs was conducted (RR 1.25, 95% CI 1.00-

1.57, I2=0%).

Conclusion: There appears to be no clear for advantage continuous renal replacement in the

hemodynamically unstable patient. Currently, both modalities are safe and effective means of

treating AKI in the critically ill adult.

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Introduction:

Acute kidney injury (AKI) is a significant contributing factor to the morbidity and mortality

of critically ill adults1;2. There are various modalities of in-hospital renal replacement

therapies (RRT) that are in use today, but the critically ill patient imposes the additional

challenge of serious hemodynamic instability which limits RRT options. The advent of

continuous renal replacement therapy (CRRT) permitted the treatment of hemodynamically

unstable AKI with tolerance for ultrafiltration, excellent control of azotemia, and potentially

less ongoing or repeated renal ischemia. The introduction of sustained low-efficiency

dialysis (SLED), which utilizes lower flow rates than conventional intermittent hemodialysis

(IHD), improve convenience by limiting therapy time while still allowing for a similar

hemodynamic tolerability to CRRT. Additionally, SLED is operationalized with IHD

equipment and does not require pre-packaged replacement solution(s). Cost savings thus

accrued has resulted in the promotion of SLED utilization in many centers3. Nevertheless,

there exists a lack of consensus regarding the optimal RRT modality for critically ill

patients. Specifically, SLED has not been universally accepted in part due to lack of

evidence for hemodynamic tolerability in specific populations with AKI and shock4. It has

been suggested that the hemodynamic stability associated CRRT compared to IHD may result

in a higher renal recovery rate5, however little data exist for a comparison of renal recovery

with SLED.

We conducted a systematic review and meta-analysis to determine the effect of the mode of

dialysis (SLED vs. CRRT) on the likelihood of renal recovery in critically ill adults. Our

secondary outcomes were to determine the effect of SLED vs. CRRT on time to renal

recovery, hemodynamic stability/vasopressor use, hypotension, and mortality.

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Methods:

This systematic review was conducted in accordance to the Preferred Reporting Items for

Systematic Reviews and Meta-Analysis (PRISMA) framework6.

Inclusion/Exclusion Criteria:

English language studies that compared any form of SLED /extended daily dialysis

(EDD)/Prolonged Intermittent Renal Replacement (PIRRT) to CRRT in hemodynamically

unstable adults (≥18 years of age) admitted to the ICU with new-onset AKI requiring renal

replacement therapy were included. Both randomized and non-randomized studies were

included, and could be of any published format (e.g. conference abstract, full manuscript).

Patients with established dialysis needs were excluded, as were those who received

intermittent hemodialysis (IHD) as the initial treatment of their AKI. Literature reviews,

systematic reviews, commentaries, case studies, pharmacological studies, and physiological

studies that did not focus on patient comparisons were also excluded.

Literature Search:

The search strategy was designed by an information specialist using a combination of

controlled vocabulary (e.g. kidney failure, intensive care units) and keywords (e.g. extended

dialysis, critical care, SLED). Vocabulary and syntax was adjusted to allow for searching on

Medline (1946 onwards), Embase (1947 onwards), CINAHL (1982 onwards), and the

Cochrane Library (available through Wiley) on Feb 22, 2015. There were no language or

date restrictions on these searches. Please see Supplementary File 1 for search strategies.

Additional studies were identified by hand searching the bibliographies of included studies

and pertinent reviews.

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Screening:

Two reviewers independently assessed all citations identified by the search strategy for

inclusion. At a title and abstract level, this was done using a liberal accelerated method7,

while assessment at the full-text level required consensus on article inclusion. Disagreements

were resolved by discussion.

Data Extraction:

Data was extracted on general study characteristics (e.g. year of publication, country of

origin, study design, sample size), demographics (e.g. patient age, gender, APACHE score,

SOFA score), and intervention design (e.g. mode of dialysis, flow rates, filtration rates).

Extracted outcome variables included the primary outcome of number of patients with renal

recovery, and second outcomes of mortality, days to renal recovery, duration of dialysis, and

complications (a composite outcome including increased vasopressor use, filter clogging,

bleeding, line sepsis, and increased hemodynamic instability). All data was extracted by one

reviewer and verified by a second investigator with all discrepancies resolved through

discussion.

Quality Assessment:

Internal validity of included studies was assessed using tools endorsed by the Cochrane

Handbook8; randomized controlled trials (RCT) were assessed using the Cochrane Risk of

Bias Tool9 while non-randomized studies were assessed using the Newcastle Ottawa scale10.

Disagreements were resolved by consensus.

Data Analysis:

The primary outcome of our analysis was the proportion of patients who recovered renal

function (defined as not requiring RRT). Secondary outcomes included time to renal

recovery, hemodynamic stability/vasopressor escalation (any increase in vasopressors dose

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from baseline prior to initiation of RRT), hypotension (blood pressure drop of > 20 point

from baseline or < 90 systolic), and mortality.

Meta-analysis of the data was conducted using random effects models for I2 greater than 30%

and fixed effects models for I2 less than 30% in Review Manager11, and results were

visualized through forest plots. Count data was expressed as summary risk ratio (RR) and

95% confidence intervals (CI), while continuous data was expressed as weighted mean

difference (MD) and 95% CI. Statistical heterogeneity of the included studies was assessed

using the I2 test and publication bias was determined using visual examination of the funnel

plot. Sensitivity analysis for randomized controlled trials were conducted for all outcomes,

when possible. Subgroup analysis was conducted for different patient populations (survivors

or all included patients), patient locations (ICU or hospital), and follow up days (e.g. 30-day

mortality).

Results:

Our literature search identified 374 articles; following deduplication 236 unique articles were

screened for inclusion. While 20 studies met a priori inclusion/exclusion criteria, one study

was a published correction12 and one was a companion13, resulting in a total of 18 studies

included in the systematic review3;14-30 (Figure 1). Studies originated from eleven different

countries, with the majority being conducted in Asia (n=8, 44%) or North America (n=5,

28%) (Table 1). Relatively few studies were randomized controlled trials (n=4, 22%), and

were published as a full manuscript (n=12, 67%) or conference abstract (n=6, 33%). They

examined a total of 1564 patients of which 738 were treated with some form of CRRT and

826 were treated with some form of SLED (Table 1). The mean patient age of all included

studies was at least 45 years but the majority were >60 years old; patients had mean study-

level APACHE II score ranging from 17.3±5.4 to 32.2±7.8, SOFA scores ranging from

7.5±2.9 to 14.2±4.2, and SAPSII scores ranging from 38.1±12.0 to 69.5±14.0. Dialysis flow

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rates were most often between 100-350 mL/h and blood flow rates were primarily between

100-200 mL/min (Table 1).

Quality assessment

While the majority of non-randomized comparative studies were assessed to have reasonable

quality for the selection category of the Newcastle-Ottawa Scale, the comparability and

outcome category were variable (Table 1). Only three studies18;19;21 of the fourteen included

studies were awarded any stars concerning comparability of cohorts, with only one study

receiving a perfect score of two stars19. Within the outcome category, very few studies

reported a sufficient follow up period for the outcome of interest and only half adequately

reported on follow up rates (Supplementary Table 1). Overall scores for outcome were

typically low, with the majority of studies receiving 2 stars or less. Unexpectedly, conference

abstracts were often of comparable methodological quality to full manuscripts (Table 1).

Randomized controlled trials showed some consistencies in their reporting (Table 2).

Allocation concealment was not described in any of the four included RCTs, and therefore

was assessed to be of an unclear risk of bias. The lack of blinding of participants and

personnel in all studies was judged to be of high risk, as this could influence patient

management and co-interventions. Any missing data observed in the studies was adequately

addressed and all expected outcomes were reported, resulting in a low risk of bias for the

items of incomplete outcome data and selective reporting. Half of the studies were

appropriately randomized and were of low risk of bias for sequence generation. Half also

indicated a lack of blinding in outcomes assessors which was judged to be a high risk as it

potentially allowed for the introduction of bias in outcome measurements. Finally, it was

unclear whether there were other sources of important bias within the studies.

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Primary Outcome: Renal Recovery

Meta-analysis of the five studies14;15;17;29;30 that assessed renal recovery showed a high degree

of statistical heterogeneity and found that there was no statistically significant difference

between CRRT and SLED (RR 0.87, 95% CI 0.63 to 1.20, I2=66%, p=0.39) (Figure 2).

However, sensitivity analysis of the two RCTs that reported this outcome indicated a

significant difference, favouring CRRT (RR 0.68, 95% CI 0.51 to 0.92, I2=0%, p=0.01)

(Figure 3). When subgroup analysis was conducted based on the patient population (all

patients or only survivors) and location (ICU or ward), statistical heterogeneity improved to

0% (Figure 4). Additionally, CRRT was associated with a significant benefit for in-

hospital14;15 (RR 0.7, 95% CI 0.52 to 0.94, I2=0%, p=0.02) and ICU14;15 (RR 0.64, 95% CI

0.43 to 0.96, I2=0%, p=0.03) renal recovery of all patients. Renal recovery for survivors was

not significantly different between treatment modalities (in-hospital14-16;23: RR 0.94, 95% CI

0.8 to 1.11, I2=0%, p=0.47; ICU14;15: RR 0.68, 95% CI 0.45 to 1.01, I2=0%, p=0.05) (Figure

3; Supplementary Figures 1-4). Within subgroups an additional sensitivity analysis of

RCTs was only needed for the outcome of in-hospital renal recovery of survivors (all other

subgroups only consisted of RCTs), which remained non-significant (RR0.67, 95% CI 0.67 to

1.04, I2=0%, p=0.11) (Supplementary Figure 5). Publication bias could not be assessed due

to an insufficient number of studies.

Secondary Outcome: Time to Renal Recovery

Three studies, all RCTs, reported on outcomes relating to time to renal recovery (total

days15;27 and number of treatments14;27 required for renal recovery). Meta-analysis indicated

that CRRT and SLED did not differ significantly regarding total days to renal recovery (MD

1.33, 95% CI -0.23 to 2.88, I2=0%, p=0.09) and number of treatments required per patient

(MD 0.65, 95% CI -0.74 to 2.04, I2=0%, p=0.36) (Figure 5 and Figure 6).

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Secondary Outcome: Mortality

A total of 16 studies provided quantitative data on mortality, allowing for a meta-analysis of

results3;14-19;22-30. Patients who received SLED were 79% less likely of dying compared to

patients receiving CRRT, a statistically significant difference (RR 1.21, 95% CI 1.02 to 1.43,

I2=47%, p=0.03) (Figure 7). Sensitivity analysis using only the four included RCTs resulted

in borderline statistical significance favouring SLED (RR 1.25, 95% CI 1.00-1.57, I2=0%,

p=0.05) (Figure 8). Subgroup meta-analysis for 30-day mortality14-17;26;30 also significantly

favoured SLED (RR 1.36, 95% CI 1.06 to 1.75, I2=0%, p=0.02), however subgroups based

on location (hospital3;14;15;19;22-24;27;28 or ICU14;15;27;30) revealed a non-significant difference

(hospital: RR 1.12, 95% CI 0.9 to 1.4, I2=56%, p=0.32; ICU: RR 1.44, 95% CI 0.93 to 2.24,

I2=56%, p=0.1) (Figure 9; Supplementary Figures 6-8). Sensitivity analysis of subgroups

supported the lack of a statistically significant difference between locations (hospital: RR

1.35, 95% CI 0.85 to 2,.16, I2=37%, p=0.21; ICU: RR 1.12, 95% CI 0.85 to 1.48, I2=29%,

p=0.42) (Supplementary Figures 9, 10). However, it also contradicted subgroup meta-

analysis results for 30-day mortality, indicating no statistically significant difference between

groups (R 1.71, 95% CI 10.95 to 3.11, I2=0%, p=0.08) (Supplementary Figure 11).

Secondary Outcome: Hypotension

Outcomes relating to hypotension, including hypotension resulting in discontinuation of

treatment15, number of patients with hypotension during dialysis29, and number of

hypotensive episodes27, showed no statistically significant differences between CRRT and

SLED. Further, Chen et al. (2012)17 reported no cases of severe intra-dialytic hypotension in

either group. Only one study showed a slight preference for CRRT relating to transient

attacks of hypotension (CRRT: n=1/40, 2.5%; SLED: n=2/40, 5%)16, however the statistical

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significance was not evaluated. Finally, one study evaluated hypotension solely in SLED

patients, and thus no conclusions could be made comparing CRRT with SLED3.

Secondary Outcome: Hemodynamic Instability/Vasopressor Use

Hemodynamic instability and vasopressor use were fairly consistent between CRRT and

SLED groups. Of the six papers3;15;19;22;23;27 and two abstracts18;20 that evaluated this

outcome, three studies were not able to show a statistically significant difference in

hemodynamic instability for the outcomes of initiation of vasopressor support15, vasopressor

dose27, and number of sessions with hemodynamic instability/vasopressor escalation19. Two

papers22;23 and two abstracts18;20 favoured SLED compared to CVVH for average number of

vasopressors per patient23, dose of vasopressors18, and number of sessions requiring

vasopressor use22, however the latter outcome was not evaluated for statistical significance22.

The final paper failed to evaluate hemodynamic outcomes for the CRRT group, and thus no

conclusions could be made3.

Discussion:

We completed this meta-analysis with the intent to determine if evidence exists regarding the

effects of SLED and CRRT on renal recovery for critically ill patients. Given the economy of

SLED, it has gained popularity in many centers and as such data concerning its efficacy on

renal recovery should also be examined.

The results of our meta-analysis indicate that no one modality (CRRT vs. SLED) was

superior concerning likelihood of renal recovery and time to renal recovery. This is

hypothesized to be due to the similarity between these modalities in terms of physiologic and

hemodynamic alternations in patients. For example, both CRRT and SLED maybe be run

continuously for 24 hours if needed with similar fluid balance. Additionally, it is possible no

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difference was observed as the only variable that may influence renal recovery is

hypotension, which was not different in the two groups. In must also be noted that sensitivity

analysis of only RCTs produced contrasting results, significantly favouring CRRT for renal

recovery in all patients. This highlights the influence of study design on resulting data, and

potentially demonstrates how selection and allocation bias, common to observational studies,

can affect outcomes. While significant differences were observed in the secondary outcome

of mortality following meta-analysis, sensitivity analysis of RCTs could only confirm a

borderline statistical significance favouring SLED with a p value of 0.05. Our systematic

review demonstrated similar results to a recently published review by Zhang et al.31, in which

sensitivity analysis of observational studies indicated a lower mortality risk for SLED

compared to CRRT while, pooling of RCT data showed no difference in mortality rates. It is

probable that this trend is due to selection bias that may be present in observational studies,

where sicker patients are more likely to receive CRRT compared to SLED. Haemodynamic

instability and vasopressor use are important contributors to morbidity and mortality.

Frequency and duration of episodes of instability and details regarding vasopressor use were

not universally reported, however in the six papers and two abstracts that did evaluate these

outcomes no statistical difference could be detected between SLED and CRRT. This was

expected as both modalities remove fluid and solute over a prolonged period of time with less

intravascular volume fluctuation as compared to the 4-6-hour period of IHD. A slower

removal of solute and fluid in an unstable patient allows for preserving a stable intravascular

volume and thereby a stable preload. Zhang et al31 also found no statistically significant

differences between these two modalities for heparin dose and episodes of vasopressor

escalation. This result may help reassure practitioners who are reluctant to switch from CRRT

to SLED because of the perception of better hemodynamic stability with CRRT.

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Only two studies reported on time to renal recovery and meta-analysis results were unable to

establish a statistically significant difference between modalities. A shorter recovery time &

fewer dialytic treatments is clearly advantageous, to both the patient and the healthcare

system through reduced costs.

Limitations and Future Directions

There are several limitations to our systematic review. Only English language articles were

included in our analysis, and as a result there is a potential that we excluded relevant articles

published in other languages. Additionally, the majority of our studies were observational

and retrospective in their study design, allowing for the introduction of error due to

confounding, allocation, and selection bias. The potential influence of study design on results

could be seen through the often-contrasting conclusions of sensitivity analysis of RCTs, when

compared to the original meta-analysis. We also allowed for the inclusion of abstracts, which

often do not provide the level of detail reviewed for thorough analysis of outcomes. Of

concern is also the moderate statistical heterogeneity observed in our meta-analysis. Finally,

the majority of studies exhibited an inadequate follow-up duration; a follow-up of at least 6-9

months is prudent for reliable and accurate assessment of renal recovery and the total

duration of dialytic treatment.

Given the limited number and varying quality of studies in this field, we can draw only some

cautious conclusions. In the future, it is recommended that authors randomize their patients

to RRT modalities, and that they follow up their patients for longer periods of time.

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Conclusion:

Renal recovery, days to renal recovery, number of treatments required for each dialysis

modality, and hemodynamic instability were not significantly different between the CRRT

and SLED treatment groups. Based on this data it is reasonable to conclude that these two

modalities of renal replacement do not produce different outcomes in adults with shock and

AKI. The overall risk of mortality was reduced in patients receiving SLED; however this

result was effectively lost when only RCTs were used for sensitivity analysis indicating

original meta-analysis results may be due to unreported complications and potentially

selection bias. Given the short follow up time of these patients and limitations of our

systematic review, we must also be careful about drawing unequivocal conclusions regarding

differences in renal recovery with currently available modes of renal replacement modalities.

Acknowledgements:

This systematic review was funded by the Ottawa Hospital Intensive Care Unit research fund.

Conflict of Interest:

The authors have no conflicts of interest to declare.

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Figure 1: PRISMA flow diagram

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Figure 2: Renal recovery in all patients treated with CRRT versus SLED

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Figure 3: Sensitivity analysis for renal recovery in all patients treated with CRRT versus SLED

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Figure 4: Subgroup analysis for renal recovery in patients treated with CRRT versus SLED

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Figure 5: Days to renal recovery in patients treated with CRRT versus SLED

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Figure 6: Number of treatments required for each dialysis modality (CRRT versus SLED)

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Figure 7: Overall mortality in patients treated with CRRT versus SLED

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Figure 8: Sensitivity analysis for mortality in all patients treated with CRRT versus SLED

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Figure 9: Subgroup analysis for mortality in patients treated with CRRT versus SLED

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 Table 1: General characteristics of included studies

Author, Study Design NOS Dialysis N Mean Sex Pre- Dialysis Blood Volume
Year Quality Method value Age±SD (M/F) treatment flow rate flow removal
Assessment (years) severity of rate
Country illness score
Kumar, Observational, S: 4 CVVH 17 48.9±20.2 12/5 APACHE II: 1000 170 3028
200022 full manuscript C: 0 17.7±7.3 mL/h mL/min mL/d
O: 0
United EDD 25 50.8±15.6 15/10 APACHE II: 300 200 3000
States 20.1±7.9 mL/min mL/min mL/d

Kumar, Observational, S: 4 CHD 28 56.7±13.7 17/11 APACHE II: 100-200 150 NR

200423 full manuscript C: 0 29.0±7.5 mL/min mL/min
O: 1 (with
United several
States treatments
at 300
mL/min)

EDD 26 47.0±12.6 26/21 APACHE II: 300 200 NR

31.8±8.5 mL/min

Berbece, Observational, S: 3 CRRT 11 55±15 7/4 APACHE II: NR 200 NR

20063 full manuscript C: 0 26.3±8 mL/min
O: 1
Canada SLED 23 60±12 14/9 APACHE II: 350 NR NR
24.4±7.3 mL/min

Majumdar, Observational, S: 4 CRRT 52 NR 34/18 APACHE II: NR NR NR

200924 conference C: 0 (median 28 (median)
abstract O: 0 age=61)
India
SLED 162 NR 99/63 APACHE II: NR NR NR
(median 26 (median)
age=66)
Marinho, Observational, S: 3 CRRT 59 NR NR NR NR NR NR
200925 conference C: 0
abstract O: 0
Portugal SLED 14 NR NR NR NR NR NR

Abe, Randomized N/A (see CVVHD 30 69.0±17.9 19/11 APACHE II: 25.9±14.2 80-200 102±29
201014 controlled trial, Table 2) F 26.2±7.3 mL/min mL/min mL/h
full manuscript SOFA:
Japan 9.0±3.2

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 S-HDF 30 68.4±15.4 20/10 APACHE II: Initial: 80-200 330±66
28.3±7.2 300 mL/min (mL/h)
SOFA: mL/min;
9.0±3.5 once
stable:
500
mL/min
Feighen, Observational, S: 4 CRRT 30 61.5±17.5 25/5 SOFA: NR 100-200 1823±14
201019 full manuscript C: 2 15.7±3.6 mL/h 64 mL
O: 2
Canada SLED 13 63.4±10.3 8/5 SOFA: 350 200 1915±13
14.0±4.1 mL/min mL/min 02
Ferrer, Observational, S: 4 CRRT 59 NR NR NR NR NR NR
201018 conference C: 1
abstract O: 1
SLED 16 NR NR NR NR NR NR
Portugal

Rittidesh, Observational, S: 4 CVVHD 12 NR NR NR NR NR NR

201026 conference C:0 F
abstract O: 0
Thailand SLED 15 NR NR NR NR NR NR

Wu, 201030 Observational, S: 3 CVVH 63 67.3±15.9 63/42 APACHE II: NR 200 NR

full manuscript C: 0 17.5±4.8 mL/min
Taiwan O: 0 SOFA:
8.3±3.0
SAPSII:
38.1±12.0

SLED 38 67.5±13.2 38/24 APACHE II: 300 200 NR

17.3±5.4 mL/min mL/min
SOFA:
7.5±2.9
SAPSII:
41.0±12.5

Abe, Randomized N/A (see CVVHD 25 65.3±13.1 17/8 APACHE II: 10.8±2.8 80-200 134±58
201115 controlled trial, Table 2) F 19.6±3.7 mL/min mL/min mL/h
full manuscript SOFA:
Japan 8.1±2.0

S-HDF 25 66.5±12.1 16/9 APACHE II: 471±27 80-200 310±70

20.0±4.3 mL/min mL/min (mL/h)
SOFA:
8.2±3.2

Grami, Observational, S: 2 CRRT NR NR NR NR NR NR NR

201120 conference C: 0
abstract O: 0
United SLED NR NR NR NR NR NR NR
States

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Khanal, Observational, S: 4 CRRT 48 58±16.1 33/15 APACHE NR 150-200 NR
201221 full manuscript C: 1 IV: mL/min
O: 2 114.9±36.7
New SOFA:
Zealand 14.2±4.2
PRITT 118 57.6±14.9 70/48 APACHE 200 200-300 NR
IV: mL/min mL/min
108.9±38.5
SOFA:
12.7±4.7
Schwenger, Randomized N/A (see CVVH 117 65.8±12.1 85/32 APACHE: NR 100-120 NR
201227 controlled trial, Table 2) 32.2±7.8 mL/min
full manuscript SAPSII:
Germany 67.7±16.7

SLED 115 66.6±12.6 72/43 APACHE: NR 100-120 NR

31.3±8.7 mL/min
SAPSII:
69.5±14.0

Badawy, Randomized N/A (see CVVHD 40 49±17 24/16 APACHE II: NR 150-200 NR
201316 controlled trial, Table 2) F 22.9±5.9 mL/min
full manuscript
Egypt EDD 40 46±18 28/12 APACHE II: 300 100-200 NR
23.3±6.2 mL/min mL/min

Chen, Observational, S: 4 CRRT 55 59.27±6.9 NR APACHE II: 300 150-200 NR

201417 full manuscript C: 0 20.5±4.57 mL/min mL/min
O: 2 SOFA:
China 13.3±2.8

SLEDD-f 52 59.83±6.7 NR APACHE II: 300 150-200 NR

20.8±3.4 mL/min mL/min
SOFA:
13.5±2.0

Shafi, Observational, S: 4 CRRT 27 45.7±NR NR APACHE II: NR NR NR

201428 conference C: 0 24±NR
abstract O: 1 SOFA:
India 11.5±NR

SLED 34 61.7±NR NR APACHE II: NR NR NR

18±NR
SOFA: 9±NR
Sun, 201429 Observational, S: 3 CVVHF 65 67.78±17. 49/16 APACHE II: NR 213.03± NR
full manuscript C: 0 55 31.10±7.23 21.72
China O: 3 SOFA: mL/min
11.98±2.92
EDHF 80 68.59±14. 59/21 APACHE II: NR 231.43± NR
97 31.20±7.12 18.26
SOFA: mL/min
12.29±3.05
Abbreviations: APACHE=Acute Physiology and Chronic Health Evaluation, C=Comparability, CHD= continuous
hemodialysis, CRRT=Continuous Renal Replacement Therapy, CVVH= Continuous Veno-Venous Hemofiltration,

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CVVHDF= Continuous Veno-Venous Hemofiltration, EDD=Extended Daily Dialysis, EDHF= extended daily
hemofiltration, NOS=Newcastle Ottawa Scale, NR=Not Reported, O=Outcome, PRITT= Prolonged
intermittent renal replacement therapy, S=Selection, SAPS=Simplified Acute Physiology Score, SD=Standard
Deviation, S-HDF=Sequential hemodiafiltration, SLED= Sustained low efficiency dialysis, SOFA=Sequential Organ
Failure Assessment

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Table 2: Cochrane Risk of Bias Quality Assessment

Item Schwenger, Abe, Abe, Badawy,

201227 201014 201115 201316

Sequence generation Low Unclear Low Unclear

Allocation concealment Unclear Unclear Unclear Unclear
Blinding of participants and High High High High
personnel

Blinding of outcomes assessors High Unclear Unclear High

Incomplete outcome data Low Low Low Low
Selective outcome reporting Low Low Low Low
Other sources of bias Unclear Unclear Unclear Unclear

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