Original Paper

Published online: June 30, 2015

Blood Purif 2015;40:8491

DOI: 10.1159/000381255

A Randomized Trial on Health-Related Patient

Satisfaction Level with High-Efficiency Online
Hemodiafiltration versus High-Flux Dialysis
AymanKarkar a MohammedAbdelrahman a FrancescoLocatelli b

Department of Nephrology, Kanoo Kidney Center, Dammam Medical Complex, Dammam, Saudi Arabia;
Department of Nephrology and Dialysis, Alessandro Manzoni Hospital, Lecco, Italy

Key Words
Dialysis adequacy Hemodialysis High-flux Health-related
satisfaction Quality of life Online hemodiafiltration
Chronic kidney disease Chronic renal insufficiency

Abstract
Background/Aim: Our aim was to investigate the effect of
on-line HDF versus high-flux (HF) hemodialysis (HD) on a patients health-related satisfaction level. Methods: Overall, 72
patients, on regular low-flux HD for 51 26 month mean age
of 54 12 years, were randomized to HF (group 1, n = 36) and
to HDF (group 2, n = 36) and followed up for 24 months.
Assessment was based on the patients satisfaction level
using modified questionnaires of the validated Kidney DiseaseQuality of Life-Short Form (KDQOL-SF) version 1.3. Results: The HDF group achieved a higher satisfaction level
than the HF group (p < 0.0001) with less cramps (3 5 vs.
55 8), itching (9 10 vs. 48 10), joint pain and stiffness
(24 10 vs. 83 8), and improvement in general mood (94
9 vs. 28 16), sexual performance (57 10 vs. 5 5), and social activity (82 9 vs. 15 8). Conclusion: High-efficiency
postdilution on-line HDF versus high-flux HD significantly
improved patients satisfaction and quality of life, including
social, physical, and professional activities.
2015 S. Karger AG, Basel

2015 S. Karger AG, Basel

02535068/15/04010084$39.50/0
E-Mail karger@karger.com
www.karger.com/bpu

Introduction

Hemodiafiltration (HDF), in which both diffusion and

convection are implemented, offers the most physiologic
clearance profile for a broad-sized range of toxic molecules
[reviewed in 1]. In randomized clinical trials, on-line HDF
showed efficient control of intradialytic hemodynamic instability and effective blood pressure control [2, 3].
Observational studies [4, 5] have shown that high-efficiency postdilution on-line HDF was associated with a
significant 35% lower mortality risk compared with lowflux HD. In the CONTRAST prospective, randomized,
and controlled study [6], there was no beneficial effect of
HDF on all-cause mortality and cardiovascular events
compared with low-flux HD. However, receiving highvolume HDF during the trial was associated with lower
all-cause mortality. Similar results were obtained in the
Turkish randomized clinical trial [7], where on-line HDF
showed no significant effect on lowering all-cause mortality in comparison to high-flux HD. The ESHOL multicenter, open-label, randomized, and controlled trial [8]
with a minimum of 18 liters/session of replacement volume showed 30 and 33% lower risk of all-cause mortality
and cardiovascular mortality, respectively, and 55% lower of infection-related mortality in high-efficiency postdilution on-line HDF compared with high-flux HD.
Ayman Karkar, PhD, FRCP, FASN
Department of Nephrology
Kanoo Kidney Center, Dammam Medical Complex
PO Box 11825, Dammam 31463 (Saudi Arabia)
E-Mail aymankarkar@yahoo.com

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Table 1. Baseline characteristics of the studied population (n = 72)

Age, years
Male, %
Female, %
Dialysis duration, months
Diabetes mellitus, %
HTN, %
CVD, %
AVF, %
Dry weight, kg
Total weight gain, kg
Body mass index, kg/m2
Blood flow rate, ml/min
Kt/V
Pre systolic BP, mm Hg
Pre diastolic BP, mm Hg
Post systolic BP, mm Hg
Post diastolic BP, mm Hg
Calcium, mg/dl
Phosphate, mg/dl
iPTH, pg/ml
Albumin, g/dl
Hemoglobin, g/dl
Transferrin saturation, %
Ferritin, ng/ml
Total iron dose, mg
Intravenous iron use, %
Darbepoetin dose, g/2 weeks
Erythropoietin use, %
Bicarbonate, mEq/l
Beta-2 microglobulin, g/l

High-flux HD
(n = 36)

On-line HDF
(n = 36)

p value

95% (CI)

53.711.4
58
42
5225
44
59
42
83
8316
3.10.9
283.9
32227
0.920.05
14211
682
1024.6
653
8.30.3
5.10.7
548175
2.940.23
9.970.61
264
597224
1,533759
88
4421
89
242
406

55.512.8
58
42
5128
50
64
44
81
8319
3.20.8
284.5
32222
0.930.13
1408
682
1026.4
662
8.40.7
5.20.7
504188
2.900.20
9.90.47
275
575171
1,463796
83
4321
86
241
416

0.52

7.7 to 4.1

0.96
0.60
0.64
0.82
0.76
0.93
0.40
0.72
0.96
0.39
0.56
0.23
0.80
0.25
0.22
0.50
0.43
0.53
0.60
0.41
0.64
0.71
0.50
0.82
0.73
0.55
0.53

9.4 to 10.2
0.3 to 0.2
0.2 to 0.1
0.12 to 0.1
0.2 to 0.02
7.5 to 8.3
0.6 to 0.2
1.6 to 2.25
12.7 to 12.1
0.02 to 0.05
3.2 to 5.8
1.3 to 0.3
5.6 to 6.9
0.6 to 2.1
0.3 to 0.1
0.4 to 0.2
61.5 to 150
0.05 to 0.1
0.2 to 0.3
4.3 to 0.85
65.8 to 110.8
416.6 to 323
0.2 to 0.1
7.4 to 9.6
0.1 to 0.2
0.6 to 1.1
2.77 to 1.1

HD = Hemodialysis; HDF = hemodiafiltration; CI = confidence interval; HTN = hypertension; CVD = cardiovascular; AVF = arterio-venous fistula; pre BP = blood pressure pre dialysis; post BP = blood pressure post dialysis; iPTH = intact parathyroid hormone;
darbepoetin = darbepoetin alpha.

Effects of High-Efficiency HDF on

Quality of Life

Study Population
Seventy-two patients previously on regular low-flux HD for
51 26 months mean age of 54 12 years 58% men were selected.
The inclusion criteria were patients aged 18 years with ESRD receiving thrice-weekly hemodialysis for 3 months. Exclusion criteria were patients who had been missing HD sessions, single-needle
dialysis, temporary nontunnelized catheter, active systemic diseases, liver cirrhosis, malignancy, and immunosuppressive therapy.
All patients had similar baseline characteristics, including blood
flow rate, single pool (sp) Kt/V, total prescribed iron dose, and
mean darbepoetin alpha dose; arteriovenous fistula and catheter
rate were 90 and 11%, respectively (table1).
The patients were randomized into two groups. Group 1 (n =
36) was switched to high-flux HD, and group 2 (n = 36) switched

Blood Purif 2015;40:8491

DOI: 10.1159/000381255

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Subjects and Methods

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Most of the observational and randomized clinical

studies focused on the beneficial effects of on-line HDF
on dialysis adequacy, hemodynamic stability, and mortality rate. However, the quality of life, well-being, and a
patients satisfaction level with HDF were evaluated by
few studies with conflicting results [9, 10]. The beneficial
effect of on-line HDF on adequate social and occupational rehabilitation was reported by Maduell et al. [2].
The primary aim of this single-center, prospective, and
randomized study was to investigate the health-related
satisfaction level of prevalent low-flux patients at baseline
and after their randomized switch to either high-flux or
high-efficiency postdilution on-line HDF, and as a secondary analyses, clinical and laboratory outcomes.

11
12
13
14
15
16
17
18

Dialysis duration/session
Dialysis sessions/week
Sickness (frequency of hypotension-related sickness)
Cramps (frequency of muscle spasm/contraction)
Itching (frequency and intensity of pruritus)
Fatigue post dialysis
General fatigue (body exhaustion)
General mood
Body energy
Hemodialysis compliance
a Regularity
b Duration
c Prescribed medications
Joint pain and stiffness
Sexual performance
Appetite
Taste
Skin color (change in color of skin from darker to lighter skin)
Social activities (participation in family and social activities)
Sport activities (physical fitness including walking)
Professional activities (work/business/studies performance)

HDF = Hemodiafiltration; HD = hemodialysis.

The assessment of the subjective response to each question was
based on a scale ranging from 0 to 100, where 0 means lowest satisfaction grade and 100 is the highest grade of satisfaction.

to high-efficiency postdilution on-line HDF with an average substitution fluid of 19.3 2.1 liters/4 h dialysis duration; both groups
were followed up for 24 months. High convection volume was
maintained by ensuring a 4 h HD session for each patient and controlling blood flow rate (using needle gauge 15 and effective vascular access). Laboratory parameters were checked at baseline, 3,
6, and 24 months. Prescription of high-flux HD and on-line HDF
included a minimum of 4 h dialysis duration performed thrice
(sessions)/week with similar high-flux dialyzers. The synthetic
high-flux dialyzers included FX60 and FX80 (Fresenius Medical
Care, Bad Homburg, Germany), and Polyflux 170H and Polyflux
210H (Gambro AB, Stockholm, Sweden). The similar percentage
treatment medications in both groups included vitamin D, noncalcium-based phosphorus binders, and calcimimetics. All patients in both groups were followed up for controlled phosphorus
diet by specialized dieticians. The composition of dialysate was the
same in both groups (sodium 138140 mmol/l, potassium 23
mmol/l, calcium 1.5 mmol/l, magnesium 0.5 mmol/l, chloride
106109 mmol/l, bicarbonate 3437 mmol/l, acetate 34 mmol/l,
and glucose 1.0 g/l). Initial assessment of the effects of postdilution
on-line HDF-treatment on a patients satisfaction level (primary
endpoint) was conducted at baseline, 3 and 6 months, and the end
of the study period (24 months), and the clinical and laboratory
outcomes (secondary endpoint) were compared with those of
high-flux HD-treated patients. All procedures were in accordance

86

Blood Purif 2015;40:8491

DOI: 10.1159/000381255

Patients Questionnaire Survey: Patients Satisfaction

To evaluate the level of a patients satisfaction with each modality of dialysis treatment, we modified and focused on sixteen questionnaires of 44 kidney disease-targeted questions of the validated
Kidney Disease Quality of Life-Short Form (KDQOL-SF) version
1.3 (http://www.rand.org/health/surveys_tools/kdqol.html) [11,
12]. These questionnaires were based on HD-associated complications that are usually of concern to dialysis patients (table2). Each
question had a score ranging from 0 to 100, where 0 indicates the
lowest satisfaction grade and 100 is the highest grade of satisfaction. The answer to each question is based entirely on the patients
own subjective assessment within the score range. The form was
distributed by the local study nurses who helped the patients fill in
the forms and showed them the way to score their answers, if necessary. Each patient, in both groups, was asked to answer a sheet
of the questionnaire at the beginning and 24 months after completion of the study. The questionnaire was answered while observing
the same duration of time for all the patients. The patients were
isolated during the administration of the questionnaire. The analysis was an intention-to-treat one. Scores were calculated, statistically analyzed, and compared between both groups at the beginning and the end of the study.
Endotoxin Measurement in the Treated Water
The reverse osmosis-treated water was assessed on a monthly
basis by the highly specific and sensitive Limulus Amebocyte
Lysate Assay (LAL) (Charles River Laboratories, Wilmington,
Mass., USA). The instrument can be used to detect endotoxin levels as high as 10 endotoxin unit (EU)/ml and as low as 0.01 EU/ml.
Statistical Analysis
Statistical analysis of the data is reported as mean standard
deviation (mean SD), and results were compared using independent samples t-tests. A p < 0.05 was considered statistically significant. Statistical analysis was performed using Medcalc software
(Broekstraat 52, B-9030, Mariakerke, Belgium) version 13.0.

Results

Effect of High-Efficiency Postdilution On-Line HDF

versus High-Flux HD on Patients Clinical Satisfaction
All patients in both groups attended all HD sessions
during the study period. The highly significant (p < 0.0001)
effects of high-efficiency postdilution on-line HDF on a
patients health-related satisfaction level versus high-flux
HD are shown in table3. These include frequency of hypotension (7 5 vs. 53 9), an effect that wasassociated
with better control of blood pressure (pre BP 129/68 vs.
140/67 mm Hg, and post BP 106/66 vs. 98/64mm Hg),
cramps (3 5 vs. 55 8), itching (9 10 vs. 4810), joint
pain and stiffness (24 10 vs. 83 8), and post-dialysis
Karkar/Abdelrahman/Locatelli

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1
2
3
4
5
6
7
8
9
10

with the ethical standards of the committee on human experimentation of our institution. Written informed consent was obtained
from each subject.

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Table 2. Modified questionnaire survey of the Kidney Disease

Quality of Life-Short Form (KDQOL-SF) version 1.3 that were
used to evaluate and compare the effects of high efficiency postdilution on-line HDF treatment with that of high-flux HD on patients compliance and satisfaction level

Sickness
(hypotension)
539
Cramps
558
Itching
4810
Post-dialysis fatigue 6118
Joint pain and
stiffness
838
General fatigue
5712
General mood
2816
Body energy
1317
Dialysis compliance 148
Regularity
Duration
Prescribed medications
Sexual performance 55
Appetite
157
Taste
3216
Skin color (lighter
change)
136
Social activity
158
Sport activity
188
Professional activity 3815

On-line p
HDF
value
at 24
months
(n = 36)

95% CI

75
35
910
109

0.0001 49.2 to 41.9

<0.0001 48.3 to 55.5
<0.0001 43.1 to 32.9
<0.0001 56.9 to 45

2410
66
949
7917
8210

<0.0001 63.3 to 54.9

<0.0001 54.8 to 46.8
<0.0001 59.6 to 72
<0.0001 63.9 to 69.5
<0.0001 70.6 to 64.5

5710
6911
7818

<0.0001 48.1 to 56.4

<0.0001 49.3 to 58.5
<0.0001 34.8 to 54.2

4022
829
589
8711

<0.0001 19.2 to 33.9

<0.0001 36.4 to 44.1
<0.0001 36.4 to 44.1
<0.0001 41.9 to 54.6

HD = Hemodialysis; HDF = hemodiafiltration; CI = confidence interval.

* Assessment was based on patients satisfaction level using
modified questionnaire survey of the Kidney Disease Quality of
Life-Short Form (KDQOL-SF) version 1.3. This was assessed by a
scale ranging from 0 to 100, where 0 reflects poor effect and 100
reflects maximum positive effect.

fatigue (10 9 vs. 61 18). Treatment with high-efficiency postdilution on-line HDF has also been associated with
improvement in general mood (949 vs. 28 16), body
energy (79 17 vs. 13 17), dialysis compliance (82 10
vs. 14 8), sexual performance (57 10 vs. 5 5), lighter
skin color (40 22 vs. 13 6), and social activity (82 9
vs. 15 8). The level of a patients satisfaction was significantly higher in postdilution on-line HDF than in the
high-flux HD, whereas it was not significantly different in
high-flux HD when compared with low-flux HD (data not
shown). Furthermore, there was no significant difference
in a patients clinical satisfaction or presenting symptoms
at 3 and 6 months between high-flux HD and on-line
Effects of High-Efficiency HDF on
Quality of Life

Effect of High-Efficiency Postdilution On-Line HDF

versus High-Flux HD on Laboratory Parameters
High-efficiency postdilution on-line HDF versus highflux HD improved spKt/V (1.33 0.14 vs. 1.21 0.11, p<
0.05), calcium (8.9 0.5 vs. 8.5 0.3 mg/dl, p < 0.0004),
phosphate (4.3 0.4 vs. 4.7 0.2 mg/dl, p < 0.0001), iPTH
(387 142 vs. 413 127 pg/ml, p < 0.0087), serum albumin (3.6 0.3 vs. 3.3 0.4 g/dl, p < 0.0001), and beta2microglobulin (21 4 vs. 30 3 g/l, p < 0.0001), respectively. The improvement in hemoglobin concentration (11.4 0.9 vs. 10.3 0.9 g/dl, p < 0.0001) was
associated with a lower total iron dose over the study period (642 627 vs. 1,411 831 mg, p < 0.0001) and darbepoetin dose (15 20 vs. 39 26 g/2 weeks, p < 0.0001),
respectively. The effects of high-efficiency postdilution
on-line HDF on all clinical and laboratory parameters
versus high-flux HD are shown in table4.
Effect of High-Flux HD or High-Efficiency
Postdilution On-Line HDF versus Low-Flux HD on
Laboratory Parameters
Compared with the baseline characteristics of lowfluxHD treatment, both high-flux HD (table5) and highefficiency postdilution on-line HDF (table6) treatments
significantly improved different laboratory parameters.
However, unlike high-flux HD, high-efficiency HDF significantly improved hemoglobin concentration (from
9.9 0.5 to 11.4 0.9 g/dl, p < 0.0001) versus high-flux
HD(from 10.0 0.6 to 10.3 0.9 g/dl, p = 0.1074); decreased darbepoetin dose (from 43 21 to 15 20 g/
2weeks, p < 0.0001 versus high-flux HD 44 21 to 39 26
g/2 weeks, p = 0.3760), total iron dose (from 1,463 796
to 642 727 mg, p < 0.0001 versus high-flux HD 1,533
759 to 1,411 831 mg, p = 0.5170), and serum ferritin level (from 575 171 to 453 97 ng/ml, p < 0.0004 versus
high-flux HD 597 224 to 541 172 ng/ml, p = 0.240).

Discussion

Our results clearly show that high-efficiency postdilution on-line HDF compared with low- and high-flux HD
significantly improved social, physical and professional
Blood Purif 2015;40:8491
DOI: 10.1159/000381255

87

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Highflux HD
at 24
months
(n = 36)

HDF-treated groups (data not shown). The reverse osmosis-treated water that was used for both studied groups of
patients consistently contained <0.1 colony factor unit
(CFU)/ml and <0.01 EU/ml. Laboratory data were not statistically different between both groups at 3 and 6 months
post-treatment (data not shown).

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Table 3. Effects of 24 months treatment with high efficiency postdilution on-line HDF, compared with the high-flux-treated group,
on health-related quality of life*

Table 4. Effects of 24 months treatment with high efficiency post-dilution on-line HDF, compared with the high-flux-treated group, on

clinical and laboratory parameters

Blood flow rate, ml/min

Kt/V
Pre systolic BP, mm Hg
Pre diastolic BP, mm Hg
Post systolic BP, mm Hg
Post diastolic BP, mm Hg
Calcium, mg/dl
Phosphate, mg/dl
iPTH, pg/ml
Albumin, g/dl
Hemoglobin, g/dl
Bicarbonate, mEq/l
Beta-2 microglobulin, g/l
Total iron dose, mg
Intravenous iron use, %
Darbepoetin dose, g/2 weeks
Erythropoietin use, %
Ferritin, ng/ml
Transferrin saturation, %
Substitution fluid (liter/treatment)

High-flux HD at
24 months
(n = 36)

On-line HDF at
24 months
(n = 36)

p value

95% CI

32831
1.210.11
1409
672
985
643
8.50.3
4.70.2
413127
3.30.4
10.30.9
251
303
1,411831
83
3926
75
541173
264

33127
1.330.13
1299
682
1067
663
8.90.5
4.30.4
387142
3.60.3
11.40.9
262
214
642627
58
1520
36
45397
287
19.32.1

0.6300
<0.0517
<0.0001
0.0509
<0.0001
0.0073
0.0002
0.0001
0.0087
<0.0001
<0.0001
0.0167
<0.0001
<0.0001
0.0194
<0.0001
0.0007
0.0095
0.1235

9.76 to 16.4
0.27 to 0.37
15.30 to 6.58
0.04 to 1.78
5.33 to 10.94
3.04 to 0.51
0.2 to 0.60
0.86 to 0.33
97 to 44.2
0.7 to 0.9
1.11 to 1.8
0.68 to 2.49
22.46 to 17.79
1,159.4 to 485.1
0.46 to 0.042
38.14 to 18.55
0.70 to 0.17
55.77 to 186.91
1.97 to 3.64

HDF = Hemodiafiltration; HD = hemodialysis; CI = confidence interval; pre BP = blood pressure pre dialysis; post BP = blood pressure
post dialysis; iPTH = intact parathyroid hormone; darbepoetin = darbepoetin alpha.

High-flux HD at
24 months
(n = 36)

p value

95% CI

32227
0.920.05
14211
682
1025
663
8.30.3
5.10.7
548175
2.90.2
10.00.6
242
406
1,533759
88
4421
89
597224
264

32831
1.210.11
1409
672
985
643
8.50.3
4.70.2
413127
3.30.4
10.30.9
251
303
1,411831
83
3926
75
541172
264

0.3770
<0.0001
0.4920
0.0855
0.0003
0.0169
0.0318
0.0483
0.0247
<0.0001
0.1074
0.5273
<0.0001
0.5170
0.5024
0.3760
0.1291
0.240
0.809

2.41 to 20.74
0.37 to 0.49
15.23 to 7.33
1.28 to 0.45
0.96 to 7.15
0.504 to 2.004
0.27 to 0.69
1.17 to 0.63
240.2 to 29.6
0.65 to 0.90
0.020 to 0.74
0.68 to 2.49
8.03 to 12.52
496.51 to 252.1
0.22 to 0.11
16.19 to 6.19
0.30 to 0.076
150.1 to 38.3
2.05 to 1.61

HD = Hemodialysis; CI = confidence interval; pre BP = blood pressure pre dialysis; post BP = blood pressure post dialysis; iPTH = intact parathyroid hormone; darbepoetin = darbepoetin alpha.

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Blood flow rate, ml/min

Kt/V
pre systolic BP, mm Hg
pre diastolic BP, mm Hg
post systolic BP, mm Hg
post diastolic BP, mm Hg
Calcium, mg/dl
Phosphate, mg/dl
iPTH, pg/ml
Albumin, g/dl
Hemoglobin, g/dl
Bicarbonate, mEq/l
Beta-2 microglobulin, g/l
Total iron dose, mg
Intravenous iron use, %
Darbepoetin dose, g/2 weeks
Erythropoietin use, %
Ferritin, ng/ml
Transferrin saturation, %

Low-flux HD at
time 0 month
(n = 36)

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Table 5. Comparing the effects of high-flux HD versus low-flux HD

Table 6. Comparing the effects of high efficiency post-dilution on-line HDF versus low-flux HD

Blood flow rate, ml/min

Kt/V
pre systolic BP, mm Hg
pre diastolic BP, mm Hg
post systolic BP, mm Hg
post diastolic BP, mm Hg
Calcium, mg/dl
Phosphate, mg/dl
iPTH, pg/ml
Albumin, g/dl
Hemoglobin, g/dl
Bicarbonate, mEq/l
Beta-2 microglobulin, g/l
Total iron dose, mg
Intravenous iron use, %
Darbepoetin dose, g/2 weeks
Erythropoietin use, %
Ferritin, ng/ml
Transferrin saturation, %

Low-flux HD
(n = 36)

On-line HDF
(n = 36)

p value

95% CI

32222
0.930.13
1408
682
1026
652
8.40.3
5.20.7
504188
2.90.2
9.90.5
23.91.4
416
1,46380
83
4321
86
575171
275

33127
1.330.14
1299
682
1065
663
8.90.5
4.30.4
387142
3.60.3
11.40.9
25.52.3
214
64273
58
1520
36
45397
287

0.1188
<0.0001
<0.0001
0.3409
0.0110
0.2368
<0.0001
<0.0001
0.0040
<0.0001
<0.0001
0.0008
<0.0001
<0.0001
0.0194
<0.0001
<0.0001
0.0004
0.5559

2.41 to 20.74
0.37 to 0.46
15.23 to 7.33
1.28 to 0.45
0.96 to 7.15
0.50 to 2.00
0.015 to 0.32
1.17 to 0.63
195.39 to 38.49
0.61 to 0.88
1.11 to 1.80
0.68 to 2.49
21.57 to 16.99
1,219.1 to 564.2
0.46 to 0.042
38.11 to 18.55
0.70 to 0.30
186.91 to 55.75
1.98 to 3.64

study did not compare the effects of high-flux HD modality versus low-flux HDF on quality of life. Mazairac
et al. [10] analyzed the data of 714 patients with a median follow-up of 2 years from the Convective Transport Study (a randomized, controlled trial on the effect
of on-line HDF versus low-flux HD on all-cause mortality). The quality of life was assessed with the Kidney
Disease Quality of Life-Short Form, where questionnaires provided data for a physical and mental composite score and described kidney disease-specific quality
of life in 12 domains (scaled from 0 to 100). This study,
which showed no significant differences in health-related quality of life over time between patients treated with
low-flux HD or HDF, did not declare the questionnaires
that were used to assess quality of life, and there was no
comparison with the effects of high-flux HD modality.
In the study of Ward et al. [15], patients were randomized to either on-line postdilution HDF or high-flux
HD. The groups did not differ in body size, treatment
time, blood flow rate, or net fluid removal, and the filtration volume in HDF was 21 1 liter. Their results
showed that on-line HDF provided superior solute removal to high-flux HD over a wide molecular-weight
range, but there was no difference in quality of life be-

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activities, body energy, dialysis compliance, sexual performance, general mood, taste, and appetite. These effects
were associated with significantly less episodes of hypotension, cramps, itching, general and post-dialysis fatigue, and joint pain and stiffness. These improvements
had a great positive impact on a patients level of satisfaction and health-related quality of life. Our data are consistent with Maduell et al. [2], who have reported a remarkable improvement in nutritional status with adequate social and occupational rehabilitation in patients
treated with on-line HDF. Our data are also in agreement
with Lin et al. [13] and Schiffl [14], who found a positive
effect of HDF on quality of life, though other studies reported either improved effect only on daily life [15] or no
effect at all [10].
The comparative effects of HD modalities, including
HDF, on quality of life of dialysis patients have been
evaluated in different studies. The study of Kantartzi et
al. [9], which compared the quality of life using the
Short-Form Health Survey with 36 questions (SF-36) in
24 patients receiving HD, on-line HDF, or bag substitution HDF for 3 months with the dialysis modality,
showed that convective modalities offer a better quality
of life than diffusive HD. However, this observational

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HDF = Hemodiafiltration; HD = hemodialysis; CI = confidence interval; pre BP = blood pressure pre dialysis; post BP = blood pressure
post dialysis; iPTH = intact parathyroid hormone; darbepoetin = darbepoetin alpha.

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cause the same effect was not seen in high-flux HD, where
the increase in Kt/V in the HDF-treated group was not
statistically significant from that of the high-flux-treated
group.
On-line HDF is empowered with biocompatible highflux membranes, ultrapure dialysate, and efficiency of removal of pro-inflammatory stimuli, including oxidative
stress molecules, advanced glycation end-products, homocysteine [22], p-cresol, and pro-inflammatory cytokines, all of which would prevent endothelial dysfunction
[23], and heavily reducing the stimulation of an inflammatory process in dialysis patients [2325]. In a metaanalysis research, ultrapure dialysate in HD patients has
been shown to result in a decrease in markers of inflammation and oxidative stress, an increase in serum albumin and hemoglobin, and a decrease in erythropoietin
dosage requirement [26]. This is in agreement with our
data where patients who were treated with high-efficiency
on-line HDF coupled with ultrapure dialysate showed
improvements in serum albumin and hemoglobin together with a reduction in requirements of darbepoetin
dose and iron supplements.
Our paper has some limitations and some strengths.
The strengths of this work include being a prospective
randomized study, lasting 24 months, with a comparison
with the previous treatment period with low-flux HD,
and using high-efficiency postdilution on-line HDF in an
important topic such as patient satisfaction not being
carefully considered in previous trials. Its limitations,
however, are that there were a relatively small number of
studied patients in each group, and using a self-administered questionnaire to assess patient satisfaction and
quality of life, where patients may either under- or overreport their true symptoms and feelings, which may lead
to misclassification bias. However, the effort of the dialysis team in trying to overcome this possible difficulty, by
adequate clarification and assistance during answering a
questionnaire, may have had alleviated such bias. Healthrelated quality of life (HRQOL) is a multidimensional
concept based on the patients subjective perception, in
which non-clinical factors such as family, friends, religious beliefs, work, income, and other life circumstances
are also involved. However, in order to maintain an optimal HRQOL in patients undergoing renal replacement,
therapy is a key element that should guide decision-making in CKD treatment programs. In this study, we only
focused on validated Kidney Disease Quality of Life-Short
Form (KDQOL-SF) version 1.3.
In conclusion, conventional HD prescription is far
from being optimal in replacing the function of normal

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tween both groups possibly due to variable and lower

HDF volume.
The findings of our prospective randomized study,
which primarily investigated the health-related satisfaction level of prevalent low-flux HD patients after their
switch to either high-flux HD or high-efficiency postdilution on-line HDF, showed that the significant benefits of
on-line HDF versus other HD modalities are novel. The
positive effects of on-line HDF on quality of life in our
patients could be due to the lower average age of our studied (rather young) patients and the achieved targeted high
volume of substitution fluids throughout the study period. Earlier studies defined replacement fluids of 514.9
liters/session as low-efficiency HDF, and replacement
fluids of 1524.9 or more liters/session as high-efficiency
HDF [16]. The data from recent randomized, controlled
studies: CONTRAST [17], Turkish [7], and ESHOL [8]
suggested that an average replacement fluid volume higher than 18 liters/session in the postdilution mode should
be targeted in order to achieve successful HDF and improve patient outcomes. Our average postdilution replacement fluids exceeded and were maintained at about
19 liters/session, and the resulting data are supporting the
ability of high-efficiency on-line HDF to improve the adequacy of dialysis and achieve significantly higher values
of Kt/V than high-flux HD [16], though this may depend
more on the duration of treatment rather than on the modality [18]. However, the study design does not have sufficient validity to ensure that the only difference lies in the
on-line HDF.
The high-efficiency postdilution on-line HDF-treated
group had significantly better clinical and laboratory results than the high-flux-treated group, confirming the results of other studies [3, 15, 1721]. Of note high-flux
treatments also significantly improved different clinical
and laboratory parameters when compared with low-flux
HD. Our data show that in terms of clinical parameters,
transition from low-flux to high-flux HD is associated
with benefits relative to clinical data but not in terms of
patient satisfaction, whereas transition from low-flux
and/or high-flux to on-line HDF causes many significant
clinical and outcome advantages.
The increase in Kt/V may not be directly related to
high-flux or HDF-treatments (their effects being usually
rather comparable and possibly negligible), but it is very
likely that the dialysis parameters were changed (although
not intentionally) and this aspect should be taken into
consideration in evaluating the effects of HDF. However,
the improvement in quality of life could be mainly related
to the HDF per se and independent of Kt/V. This is be-

kidneys, and it has been associated with unacceptable

high rates of cardiovascular morbidity, mortality, and
poor quality of life. In our study, high-efficiency postdilution on-line HDF in comparison to high-flux HD improved patients satisfaction and health-related quality of
life.

Disclosure Statement
Conflict of interest statement: None declared from A.K., M.A.
and F.L. was the principal Investigator of the MPO study supported by Fresenius and of the Italian Convective study partially supported by Gambro and members of the EUDIAL group of ERAEDTA.

References
10 Mazairac AH, de Wit GA, Grooteman MP,
Penne EL, van der Weerd NC, den Hoedt
CH,Lvesque R, van den Dorpel MA, Nub
MJ, ter Wee PM, Bots ML, Blankestijn PJ;
CONTRAST Investigators: Effect of hemodiafiltration on quality of life over time. Clin J
Am Soc Nephrol 2013;8:8289.
11 Hays RD, Kallich JD, Mapes DL, Coons SJ,
Carter WB: Development of the kidney disease quality of life (KDQOL) instrument.
Qual Life Res 1994;3:329338.
12 Korevaar JC, Merkus MP, Jansen MA, Dekker
FW, Boeschoten EW, Krediet RT; NECOSADstudy group: Validation of the KDQOL-SF: a
dialysis-targeted health measure. Qual Life
Res 2002;11:437447.
13 Lin CL, Huang CC, Chang CT, Wu MS, Hung
CC, Chien CC, Yang CW: Clinical improvement by increased frequency of on-line hemodialfiltration. Ren Fail 2001;23:193206.
14 Schiffl H: Prospective randomized cross-over
long-term comparison of online haemodiafiltration and ultrapure high-flux haemodialysis. Eur J Med Res 2007;12:2633.
15 Ward RA, Schmidt B, Hullin J, Hillebrand
GF, Samtleben W: A comparison of on-line
hemodiafiltration and high-flux hemodialysis: a prospective clinical study. J Am Soc
Nephrol 2000;11:23442350.
16 Canaud B, Bragg-Gresham JL, Marshall MR,
Desmeules S, et al: Mortality risk for patients
receiving hemodiafiltration versus hemodialysis: European results from the DOPPS.
Kidney Int 2006;69:20872093.
17 Penne EL, Blankestijn PJ, Bots ML, et al: Effect
of increased convective clearance by on-line
hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients the Dutch CONvective TRAnsport
STudy (CONTRAST): rationale and design
of a randomised controlled trial [ISRCTN
38365125]. Curr Control Trials Cardiovasc
Med 2005;6:8.
18 Cornelis T, van der Sande FM, Eloot S, Cardinaels E, Bekers O, Damoiseaux J, Leunissen

19

20

21

22

23

24

25

26

KM, Kooman JP: Acute hemodynamic response and uremic toxin removal in conventional and extended hemodialysis and hemodiafiltration: a randomized crossover study.
Am J Kidney Dis 2014;64:247256.
Pedrini LA, De Cristofaro V, Comelli M, Casino
FG, et al: Long-term effects of high-efficiency
on-line haemodiafiltration on uraemic toxicity.
A multicentre prospective randomized study.
Nephrol Dial Transplant 2011;26:26172624.
Basile C: The effect of convection on the nutritional status of haemodialysis patients.
Nephrol Dial Transplant 2003;18:vii46vii49;
discussion vii58vii59.
Davenport A, Gardner C, Delaney M: The effect of dialysis modality on phosphate control:
haemodialysis compared to haemodiafiltration. The Pan Thames Renal Audit. Nephrol
Dial Transplant 2010;25:897901.
Badiou S, Morena M, Bargnoux AS, Jaussent
I, et al: Does hemodiafiltration improve the
removal of homocysteine? Hemodial Int
2011;15:515521.
Bellien J, Frguin-Bouilland C, Joannids R,
Hanoy M, Rmy-Jouet I, et al: High-efficiency
on-line haemodiafiltration improves conduit
artery endothelial function compared with
high-flux haemodialysis in end-stage renal
disease patients. Nephrol Dial Transplant
2014;29:414422.
Ramirez R, Carracedo J, Merino A, Nogueras
S, et al: Microinflammation induces endothelial damage in hemodialysis patients: the role
of convective transport. Kidney Int 2007; 72:
108113.
den Hoedt CH, Bots ML, Grooteman MP, van
der Weerd NC, Mazairac AH, et al: Online hemodiafiltration reduces systemic inflammation compared to low-flux hemodialysis. Kidney Int 2014;86:423432.
Susantitaphong P, Riella C, Jaber BL: Effect of
ultrapure dialysate on markers of inflammation, oxidative stress, nutrition and anemia
parameters: a meta-analysis. Nephrol Dial
Transplant 2013;28:438446.

Effects of High-Efficiency HDF on

Quality of Life

Blood Purif 2015;40:8491

DOI: 10.1159/000381255

91

Downloaded by: C. Lavorato

198.143.56.33 - 1/25/2016 5:55:42 PM

- 31217

1 Karkar A: Modalities of hemodialysis: quality

improvement. Saudi J Kidney Dis Transpl
2012;23:11451161.
2 Maduell F, Arias M, Durn CE, Vera M, et al:
Nocturnal, every-other-day, online haemodiafiltration: an effective therapeutic alternative. Nephrol Dial Transplant 2012; 27: 1619
1631.
3 Locatelli F, Altieri P, Andrulli S, Bolasco P, et
al: Hemofiltration and hemodiafiltration reduce intradialytic hypotension in ESRD. J Am
Soc Nephrol 2010;21:17981807.
4 Vilar E, Fry AC, Wellsted D, Tattersall JE, et
al: Long-term outcomes in online hemodiafiltration and high-flux hemodialysis: a comparative analysis. Clin J Am Soc Nephrol
2009;4:19441953.
5 Jirka T, Cesare S, Di Benedetto A, et al: Mortality risk for patients receiving hemodiafiltration versus hemodialysis. Kidney Int 2006;
70:1524; author reply 15241525.
6 Grooteman MP, van den Dorpel MA, Bots
ML, Penne EL, van der Weerd NC, et al: Effect
of online hemodiafiltration on all-cause mortality and cardiovascular outcomes. J Am Soc
Nephrol 2012;23:10871096.
7 Ok E, Asci G, Toz H, Ok ES, Kircelli F, et al:
Mortality and cardiovascular events in onlinehaemodiafiltration (OL-HDF) compared
with high-flux dialysis: results from the
Turkish OL-HDF Study. Nephrol Dial Transplant 2013;28:192202.
8 Maduell F, Moreso F, Pons M, Ramos R, Mora-Maci J, et al: High-efficiency postdilution
online hemodiafiltration reduces all-cause
mortality in hemodialysis patients. J Am Soc
Nephrol 2013;24:487497.
9 Kantartzi K, Panagoutsos S, Mourvati E,
Roumeliotis A, Leivaditis K, Devetzis V,
Passadakis P, Vargemezis V: Can dialysis
modality influence quality of life in chronic hemodialysis patients? Low-flux hemodialysis versus high-flux hemodiafiltration: a cross-over study. Ren Fail 2013; 35:
216221.