Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Rabindranath, 2007

SR and meta-analysis of RCTs

Literature search up to October, 2006

A: Augustine, 2004

B: Gasparovic, 2003

C: Mehta, 2001

D: Noble, 2006

E: Uehlinger, 2005

F: Visonneau, 2006

G: John, 2001

Study design: RCT

Setting and Country:

A: University teaching hospital, USA

B: University hospital, Croatia

C: Multicentre trial, USA

D: University teaching hospital, UK

E: ICU in the University Hospital of Berne, Switzerland

F: Multicentre, France

G: University teaching hospital, Germany

Source of funding and conflicts of interest:

Funding not reported.

No potential conflict of interest to declare.

Inclusion criteria SR:

Randomised controlled trials (RCTs - either parallel or crossover design) in which patients have been allocated to treatment with IRRT or CRRT for ARF and reporting outcomes of interest to this review; All adult patients (≥ 18 years) requiring RRT for ARF were considered eligible for inclusion. It was planned that if there are sufficient number of studies subgroup analysis according to varying degrees of comorbidity will also be undertaken.

Exclusion criteria SR:

RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods; studies of peritoneal dialysis were not considered in this review.

7 studies published after 2000 were included in the analysis

Population:

N total, CRRT, IRRT

A: 80, 40, 40

B: 104, 52, 52

C: 166, 84, 82

D: 94, 54, 40

E: 129, 70, 55

F: 360, 176, 184

G: 30, 20, 10

Participants

A: age 61y, 68% male, surgery 65%

B: Sepsis 77%, mean APACHE II 20.9, mean SOFA 10.4

C: Age 55y, 65% male, APACHE II 24, APACHE III 92, surgery 27%.

D: Age 53y, 75% male, surgical 49%, sepsis 58%.

E: Age 67y, 67% male, sepsis 47%, SAPS score 55.

F: Age 65y, 73% male, SAPS II score 64.5, 62% sepsis.

G: All patients had septic shock; age 62y, 87% male, APACHE II 33.5.

CRRT was defined as any form of RRT (HD, HF, HDF,

UF) that was intended to run on a continuous basis until recovery of renal function occurred.

A: CVVHD; Low-flux polysulfone membrane; Blood flow rate: 200 mL/min; Dialysate flow varied according to dry weight; Bicarbonate dialysate: 35 mEq/L; Anticoagulation: Heparin; Dose adjusted to achieve weekly Kt/V of 3.6.

B: CVVHF; First 33 patients had low volume HF (18 mL/kg/h) and the next had high volume HF (35 mL/kg/h); using polysulfone membrane.

C: CAVHDF in the first two years followed by CVVHDF in the following years; Polysulfone or polyacrylonitrile membranes; Blood flow: 100 mL/min; Dialysate flow rate: 16.7 mL/min; Ultrafiltration rate: 400-800 mL/h; Anticoagulation: Heparin, citrate or saline flushes; At least 25 hours treatment was considered necessary as satisfactory intervention period.

D: CHD via a Scribner shunt or venous dialysis catheter; Bicarbonate dialysate; Blood flow: 150 mL/min; Dialysate flow:300-500 mL/min; Dialysis membranes: Fresenius polysulfone.

E: CVVHDF; Membrane: AN69 high-flux hemofilter;

Blood flow: 100-180 mL/min; Standard lactate-buffered fluid was used as dialysate and a substitute at a combined rate of 2000 mL/h; Fluids given in a predilution fashion.

F: CVVHDF; Blood flow: >/= 120 mL/min; Dialysate flow: >/= 500 mL/h; Ultrafiltration flow> >/= 1000 mL/h; Membrane: Polyacrylonitrile.

G: CVVHF; High-flux polysulfone membranes

Fluid removal was between 1.2-1.8 L/24 h; Vasopressor support increased during RRT to maintain MAP not lower than 20% of baseline; Blood flow: 250 mL/min; Ultrafiltration rate: 2 L/h; Fluids rewarmed to 37C and infused post-dilutionally.

IRRT was defined as any form of RRT (haemodialysis

(HD), haemofiltration (HF), haemodiafiltration (HDF), isolated ultrafiltration (UF)) prescribed for a period of < 24 hours within any 24 hour period.

A: IHD 3 times/week; Low-flux polysulfone; Blood flow rate: 300 mL/min; Dialysate flow: 500 mL/min; Duration of HD varied to achieve weekly Kt/V of 3.6.

B: IHD; 3-4 hour treatments; Blood flow: 200-250 mL/min; Dialysate flow: 500 mL/min; Membrane: polysulfone, most frequently without heparin.

C: IHD using bicarbonate dialysate; Dialysate flow rate: 500 mL/min; Blood flow rate: 200-300 mL/min; Both cellulose and synthetic membranes were used; At least 2 sessions of at least 3 hours each was necessary for considering as successful intervention.

D: IHD; Cuprophane membranes for 4 h/d every day

E: IHD; Membrane: Polysulfone; Blood flow: 150-300 mL/min; Bicarbonate buffered dialysate was used; Ultrafiltration rate: 250-1000 mL/h; Usual HD session lasted for 3-4 hours.

F: Blood flow: >/= 250 mL/min; Dialysate flow: 500 mL/min; To achieve optimum haemodynamic stability a high sodium concentration (150 mmol/L) dialysate at a low temperature (35°C) was used; Therapy was started simultaneously connecting to the catheter both lines of the circuit filled with 0·9% saline (isovolemic connection), be applied for at least 4 h, and be given every 48 h if anuria or oliguria were present. In other cases, the frequency was defined to maintain a urea concentration of less than 40 mmol/L; Membrane: Polyacrylonitrile.

G: IHD; Low-flux polysulfone membranes for 4 hours; Fluid removal was between 1.2-1.8 L/24 h; Vasopressor support increased during RRT to maintain MAP not lower than 20% of baseline; Blood flow: 250 mL/min; Bicarbonate-based dialysate.

End-point of follow-up:

A: death or hospital discharge

B: 21 days

C: death or hospital discharge

D: death or hospital discharge

E: death or hospital discharge

F: 90 days

G: 24 hours

For how many participants were no complete outcome data available?

A: 0/80

B: 0/104

C: 0/166

D: 0/94

E: 0/129

F: 0/360

G: 0/30

In-hospital mortality

A: CRRT 27/40; IRRT 28/40

B: CRRT 37/52; IRRT 31/52

C: CRRT 55/84; IRRT 39/82

D: CRRT 43/54; IRRT 34/40

E: CRRT 33/70; IRRT 28/55

F: CRRT 118/176; IRRT 126/184

Pooled RR (random effects model):

1.03 (95% CI 0.92, 1.16)

Heterogeneity (I²): 33%

ICU mortality

G: CRRT 14/20; IRRT 7/10

C: CRRT 50/84; IRRT 34/82

D: CRRT 43/54; IRRT 34/40

E: CRRT 24/70; IRRT 21/55

Pooled RR (random effects model):

1.06 (95% CI 0.83, 1.35)

Heterogeneity (I²): 53%

Recovery of renal function

A: CRRT 5/13; IRRT 4/12

C: CRRT 25/29; IRRT 40/43

E: CRRT 36/37; IRRT 26/27

Pooled RR (random effects model):

0.99 (95% CI 0.92, 1.07)

Heterogeneity (I²): 0%

Length of ICU stay

Mean±SD, in days

A: CRRT 35.8±20.5, n=13;

IRRT 41.9±30.1, n=12

John (2001) is the only study a septic shock population. Due to the limited population size, analysis is extended to ICU/critically ill population.

Studies that completed patient inclusion before 2000 were excluded from the literature analysis.

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Lins, 2008

(SHARF4, NCT 00322933)

Type of study:

RCT

Setting and country: Belgian multicentre trial in hospitals with at least 600 beds, a centre for the treatment of endstage kidney disease patients, a multipurpose ICU with at least 12 beds, at least 30 patients with AKI treated with RRT during the past year and regular use of both intermittent and continuous techniques.

Funding and conflicts of interest:

Sources of funding not specified. The authors declare no conflict of interest.

Inclusion criteria:

Adult AKI patients with a serum creatinine >2 mg/dL (177 µmol/L) that were consecutively admitted in the participating centres, with the need for RRT, as decided by the attending physician.

Exclusion criteria:

Pre-existing chronic renal disease, defined as a serum creatinine >1.5 mg/dL (133 µmol/L) or with the clearly reduced kidney size on ultrasound.

N total at baseline:

IRRT: 144

CRRT: 172

Age (range):

IRRT: 67 (20-96)

CRRT: 65 (18-89)

Sex (% male):

IRRT: 58

CRRT: 60

APACHE II:

IRRT: 27.1±11.5

CRRT: 26.3±11.2

SOFA 0:

IRRT:10.8±3.4

CRRT: 10.7±3.4

Groups were comparable at baseline

For IRRT, a central venous access, a biocompatible membrane (polysulfone or AN 69) and bicarbonate dialysate were used. Daily dialysis was performed during 4–6 h per session with a blood flow of 100–300 mL/min and a dialysate flow of 300–500 mL/min.

For CRRT, a central venous access, a biocompatible membrane (polysulfone or AN 69) and post-dilution continuous veno-venous haemofiltration (CVVH) were used. It was continued during 24 h/day with a blood flow rate of 100–250 mL/min, an ultrafiltration rate of 1–2 L/h and either lactate or bicarbonate solutions were used.

For both modalities, anticoagulation was performed according to the centre practice, either with unfractionated heparin, low molecular weight heparin or citrate.

Treatment continued daily during at least 3 consecutive days. Thereafter treatment could be continued according to the needs of the patients.

Length of follow-up:

Death or hospital discharge.

Loss-to-follow-up:

None

Incomplete outcome data:

Not reported

Hospital mortality

IRRT 62.5%

CRRT 58.1%

P=0.430

Renal recovery

CKD stage 1-2

IRRT 29.8%

CRRT 28.8%

CKD stage 3

IRRT 29.8%

CRRT 28.8%

CKD stage 4

IRRT 14.9%

CRRT 25.5%

CKD stage 5

IRRT 25.5%

CRRT 16.9%

P=0.474

Hospital length of stay

IRRT 31.4±29.7

CRRT 36.8±31.0

P=0.345

ICU length of stay

IRRT 17.2±18.7

CRRT 18.7±19.0

P=0.510

205 (65%) patients sepsis

In deze groep mortaliteit 70,5% IRRT en 64% CRRT

Underpowered: Recruitment of patients ended before the required sample size was reached. (407 patients per treatment group according to power calculation)

Of the 650 eligle patients 124 patients (37%) were excluded for medical reasons (coagulation disturbances and haemodynamic instability)

Cross-over during first 3 days: from IRRT to CRRT in 11 patients because of haemodynamic instability.

Cross-over from CRRT to IRRT in 12 patients because of coagulation problems

No information on delivered dose and cumulative fluidbalance

Schefold, 2014

(CONVINT trial)

Type of study:

RCT

Setting and country:

Single center, university hospital Berlin, Germany.

Funding and conflicts of interest:

The authors declare that they have no conflict of interest, financially or otherwise, to disclose.

Inclusion criteria:

Adult patients with AKI requiring RRT treated at the medical intensive care units. Need for RRT was defined as presence of at least one of the following criteria: (a) clinical symptoms of uremia; (b) persisting oliguria or anuria despite adequate fluid management; (c) fluid overload not responding to diuretic treatment; (d) blood urea nitrogen (BUN) levels >100 mg/dl (35 mmol/L) or creatinine clearance <0.1 ml/ kg of body weight/min; (e) severe metabolic acidosis (pH <7.2) not responding to conventional treatment; and (f) hyperkalemia

not responding to conservative treatment.

Exclusion criteria:

(a) preexisting chronic renal failure with serum creatinine >3 mg/dl (265 µmol/L) or patients receiving chronic dialysis; (b) kidney-transplant recipients; (c) patients not requiring ICU treatment; (d) denial of written informed consent.

N total at baseline:

Intervention: 128

Control: 122

Age mean ± SD:

I: 60.8±13.4

C: 62.3±14.5

Sex (% male):

I: 63

C: 62

APACHE II

I: 28.5±7.9

C: 28.8±9.6

SAPS II

I: 66.1±18.1

C: 63.8±17.6

SOFA:

I: 13.2±3.9

C: 13.0±4.0

Sepsis-induced ARF:

I: 66.4%

C: 69.7%

Groups were comparable at baseline

Standard treatment dose was daily IHD with 4 hours of hemodialysis at a blood flow of 200 to 250 ml/min. A dialysate flow at 500 ml/min, volumetric UF-control, water purified by reverse osmosis, and bicarbonate dialysate was used.

Postdilutional CVVH (BM11/BM14; Baxter Medical, Deerfield, IL, USA, or Multifiltrate, Fresenius Medical Care, Bad Homburg, Germany) was applied 24 hours daily by using a polysulfone synthetic membrane, blood flow of 200 ml/min, prescribed filtration rate of 35 ml/ kg of body weight/hour, by using bicarbonate-buffered substitution fluids.

General treatment target in both groups was absence of any criteria for acute RRT and a target-time-averaged serum urea of 100 to 150 mg/dl every 72 hours (mean pre + post + pre in IHD; not intended as an outcome measure).

CVVH membranes were exchanged every 24 hours in patients with severe sepsis/septic shock. In all other patients, membranes were exchanged every 48 hours.

Length of follow-up:

Death or hospital discharge

Loss-to-follow-up:

None reported

Incomplete outcome data:

Not reported

Hospital mortality

IHD 60.3%

CVVH 54.6%

P=0.72

14-day mortality

IHD 43.6%

CVVH 37.8%

P=0.63

30-day mortality

IHD 52.4%

CVVH 45.4%

P=0.60

Renal recovery (60 days)

IHD 73.6%

CVVH 77.2%

P=0.90

Hospital length of stay (days)

IHD 33.9±49.3

CVVH 32.4±37.4

P=0.79

ICU length of stay (days)

IHD 25.2±40.1

CVVH 22.3±26.1

P=0.50

Duration of RRT (days)

IHD 17.2±37.1

CVVH 13.7±17.9

P=0.35

Dialysis free days

IHD: 4.2 ± 9.6

CVVH: 3.1 ± 9.0

P=0.38

Number of patients on RRT (% of survivors) at day 21

IHD: 20 (32.3%)

CVVH: 20 (29.9%)

P=0.97

At day 60

IHD: 14 (26.4%)

CVVH: 13 (22.8%)

P=0.90

Underpowered: power calculation 200 patients per arm. Sample size 125 patients per arm

Major reasons for development of AKI was severe sepsis/septic shock (both groups > 65% of study patients at baseline)

Crossover: From IHD to CVVH 25 (19,5%) for hemodynamic instability and/or significant fluid overload

From CVVH to IHD 56 (45,9%) for repeated filter clotting, metabolic reasons, coagulation disbalance, desired mobilization of study patient.

Study

First author, year

Appropriate and clearly focused question?¹

Yes/no/unclear

Comprehensive and systematic literature search?²

Yes/no/unclear

Description of included and excluded studies?³

Yes/no/unclear

Description of relevant characteristics of included studies?⁴

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?⁵

Yes/no/unclear/notapplicable

Assessment of scientific quality of included studies?⁶

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?⁷

Yes/no/unclear

Potential risk of publication bias taken into account?⁸

Yes/no/unclear

Potential conflicts of interest reported?⁹

Yes/no/unclear

Rabindrabath, 2007

Yes

Yes

Yes

Yes

N/A

Yes

Yes

Yes

Unclear

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome accessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Lins, 2008

Separately for each participating centre, the choice of RRT treatment modality was randomized within each stratum of the SHARF score. Stratified block randomization was achieved within the electronic case report form(CRF) using a computer-generated sequence of random numbers. If the investigator decided not to randomize, the program was electronically blocked until he completed the reason for non-randomization.

Unclear

unlikely

Likely

Not blinded.

unclear

unlikely

unlikely

unlikely

Schefold, 2014

Patients were allocated to the respective study groups at study day 0 (day of randomization; 1). To assure concealment of allocation, an independent external telephone (computer-based) randomization procedure provided by the Department of Biometry and Medical Documentation, University of Ulm, Ulm, Germany, was used (permutated blocks of four).

Unclear

unlikely

Likely

Not blinded.

unclear

unlikely

unlikely

unlikely