Introduction: Endothelial dysfunction (ED) is considered a marker of vascular complications, especially in patients with end-stage kidney disease (ESKD). Inflammation and the uremic state contribute to ED in patients undergoing hemodialysis (HD). Recently, the medium cut-off (MCO) dialysis membrane has been proposed to efficiently remove inflammatory cytokines and large, middle-sized uremic toxins, with the potential effect to improve endothelial function. This study aimed to compare the effect of dialysis with MCO or high-flux membranes on the endothelial function of patients on chronic HD. Methods: A prospective, randomized, crossover study in which 32 patients with ESKD were dialyzed for 12 weeks with each membrane, including a 4-week washout period between treatments. Endothelial function was assessed by flow-mediated dilation (FMD) using brachial artery ultrasound at weeks 1, 12, 16, and 28. Results: The population consisted of 59% men, 52.7 ± 13.4 years, 16% non-black, on HD for 8.8 (4.1–15.1) years, and 72% with arteriovenous fistula. Hypertension was the most common etiology of chronic kidney disease, and 34% of patients had previous cardiovascular disease. Patients were grouped, regardless of treatment sequence, into MCO or high-flux groups, since no carryover (p = 0.634) or sequence (p = 0.998) effects were observed in the FMD assessment. The ANOVA model with repeated measures showed no effects of treatment (p = 0.426), time (p = 0.972), or interaction (p = 0.413) in the comparison of FMD between the MCO and high-flux groups. Conclusion: Dialysis performed with MCO, or high-flux membranes, had no influence on endothelial function in patients undergoing HD. However, a trend towards increased FMD was observed with the use of the MCO membrane.

1.
Levin
A
.
Clinical epidemiology of cardiovascular disease in chronic kidney disease prior to dialysis
.
Semin Dial
.
2003
;
16
(
2
):
101
5
. .
2.
Cozzolino
M
,
Galassi
A
,
Pivari
F
,
Ciceri
P
,
Conte
F
.
The cardiovascular burden in end-stage renal disease
.
Contrib Nephrol
.
2017
;
191
:
44
57
. .
3.
Foley
RN
,
Parfrey
PS
,
Sarnak
MJ
.
Clinical epidemiology of cardiovascular disease in chronic renal disease
.
Am J Kidney Dis
.
1998
;
32
(
5 Suppl 3
):
S112
9
. .
4.
Kahn
MR
,
Robbins
MJ
,
Kim
MC
,
Fuster
V
.
Management of cardiovascular disease in patients with kidney disease
.
Nat Rev Cardiol
.
2013
;
10
(
5
):
261
73
. .
5.
Zoccali
C
,
Mallamaci
F
,
Tripepi
G
.
Traditional and emerging cardiovascular risk factors in end-stage renal disease
.
Kidney Int
.
2003
;
63
(
85
):
S105
10
. .
6.
Zoccali
C
.
Traditional and emerging cardiovascular and renal risk factors: an epidemiologic perspective
.
Kidney Int
.
2006
;
70
(
1
):
26
33
. .
7.
Zoccali
C
,
Mallamaci
F
,
Tripepi
G
.
Novel cardiovascular risk factors in end-stage renal disease
.
J Am Soc Nephrol
.
2004
;
15
(
Suppl l
):
S77
80
. .
8.
Glorieux
G
,
Vanholder
R
.
New uremic toxins: which solutes should be removed
.
Contrib Nephrol
.
2011
;
168
:
117
28
. .
9.
Lisowska-Myjak
B
,
Lisowska-Myjak
B
.
Uremic toxins and their effects on multiple organ systems
.
Nephron Clin Pract
.
2014
;
128
(
3–4
):
303
11
. .
10.
Harlacher
E
,
Wollenhaupt
J
,
Baaten
CCFMJ
,
Noels
H
,
Noels
H
.
Impact of uremic toxins on endothelial dysfunction in chronic kidney disease: a systematic review
.
Int J Mol Sci
.
2022
;
23
(
1
):
531
. .
11.
Gennip
ACEV
,
Broers
NJH
,
Meulen
KJT
,
Canaud
B
,
Christiaans
MHL
,
Cornelis
T
, et al
.
Endothelial dysfunction and low-grade inflammation in the transition to renal replacement therapy
.
PLoS One
.
2019
;
14
(
9
):
e0222547
. .
12.
Cavallari
C
,
Dellepiane
S
,
Fonsato
V
,
Medica
D
,
Marengo
M
,
Migliori
M
, et al
.
Online hemodiafiltration inhibits inflammation-related endothelial dysfunction and vascular calcification of uremic patients modulating miR-223 expression in plasma extracellular vesicles
.
J Immunol
.
2019
;
202
(
8
):
2372
83
. .
13.
Miyazaki
H
,
Matsuoka
H
,
Itabe
H
,
Usui
M
,
Ueda
S
,
Okuda
S
, et al
.
Hemodialysis impairs endothelial function via oxidative stress: effects of vitamin E-coated dialyzer
.
Circulation
.
2000
;
101
(
9
):
1002
6
. .
14.
Malyszko
J
,
Malyszko
J
.
Mechanism of endothelial dysfunction in chronic kidney disease
.
Clin Chim Acta
.
2010
;
411
(
19–20
):
1412
20
. .
15.
Konukoglu
D
,
Uzun
H
.
Endothelial dysfunction and hypertension
.
Adv Exp Med Biol
.
2016
;
956
:
511
40
. .
16.
Sena
CM
,
Pereira
AM
,
Seiça
R
.
Endothelial dysfunction - a major mediator of diabetic vascular disease
.
Biochim Biophys Acta
.
2013
;
1832
(
12
):
2216
31
. .
17.
Lekakis
J
,
Abraham
P
,
Balbarini
A
,
Blann
AD
,
Boulanger
CM
,
Cockcroft
JR
, et al
.
Methods for evaluating endothelial function: a position statement from the European society of cardiology working group on peripheral circulation
.
Eur J Cardiovasc Prev Rehabil
.
2011
;
18
(
6
):
775
89
. .
18.
Inoue
T
,
Matsuoka
H
,
Ueda
SI
,
Higashi
Y
,
Sata
M
,
Shimada
KE
, et al
.
Flow-mediated vasodilation as a diagnostic modality for vascular failure
.
Hypertens Res
.
2008
;
31
(
12
):
2105
13
. .
19.
Corretti
MC
,
Anderson
TJ
,
Benjamin
EJ
,
Celermajer
DS
,
Charbonneau
F
,
Creager
MA
, et al
.
Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force
.
J Am Coll Cardiol
.
2002
;
39
(
2
):
257
65
. .
20.
Moens
AL
,
Goovaerts
I
,
Claeys
MJ
,
Vrints
CJ
.
Flow-mediated vasodilation: a diagnostic instrument, or an experimental tool
.
Chest
.
2005
;
127
(
6
):
2254
63
. .
21.
Wung
CH
,
Wang
Y-H
,
Lee
Y-C
,
Chang
C-W
,
Wu
PY
,
Huang
JC
, et al
.
Association between flow-mediated dilation and skin perfusion pressure with peripheral artery disease in hemodialysis patients
.
J Pers Med
.
2021
;
11
(
12
):
1251
. .
22.
Liakopoulos
V
,
Roumeliotis
S
,
Gorny
X
,
Dounousi
E
,
Mertens
PR
,
Mertens
PR
.
Oxidative stress in hemodialysis patients: a review of the literature
.
Oxid Med Cell Longev
.
2017
;
2017
:
3081856
. .
23.
Jourde-Chiche
N
,
Dou
L
,
Cerini
C
,
Dignat-George
F
,
Brunet
P
,
Brunet
P
.
Vascular incompetence in dialysis patients: protein-bound uremic toxins and endothelial dysfunction
.
Semin Dial
.
2011
;
24
(
3
):
327
37
. .
24.
Ronco
C
,
La Manna
G
,
La Manna
G
.
Expanded hemodialysis: a new therapy for a new class of membranes
.
Contrib Nephrol
.
2017
;
190
:
124
33
. .
25.
Ronco
C
,
Clark
WR
,
Clark
WR
.
Haemodialysis membranes
.
Nat Rev Nephrol
.
2018
;
14
(
6
):
394
410
. .
26.
Lorenzin
A
,
Neri
M
,
Lupi
A
,
Todesco
M
,
Santimaria
M
,
Alghisi
A
, et al
.
Quantification of internal filtration in hollow fiber hemodialyzers with medium cut-off membrane
.
Blood Purif
.
2018
;
46
(
3
):
196
204
. .
27.
Hutchison
CA
,
Wolley
M
,
Wolley
M
.
The rationale for expanded hemodialysis therapy (HDx)
.
Contrib Nephrol
.
2017
;
191
:
142
52
. .
28.
Yilmaz
MI
,
Stenvinkel
P
,
Sonmez
A
,
Saglam
M
,
Yaman
H
,
Kilic
S
, et al
.
Vascular health, systemic inflammation and progressive reduction in kidney function; clinical determinants and impact on cardiovascular outcomes
.
Nephrol Dial Transplant
.
2011
;
26
(
11
):
3537
43
. .
29.
Marincowitz
C
,
Webster
I
,
Westcott
C
,
Goswami
N
,
De Boever
P
,
Seidel
G
, et al
.
Vascular health assessment with flow-mediated dilatation and retinal image analysis: a pilot study in an adult population from Cape Town
.
Cardiovasc J Afr
.
2020
;
31
(
3
):
1
8
.
30.
Heiss
C
,
Rodriguez-Mateos
A
,
Bapir
M
,
Skene
SS
,
Sies
H
,
Kelm
M
.
Flow-mediated dilation reference values for evaluation of endothelial function and cardiovascular health
.
Cardiovasc Res
.
2023
;
119
(
1
):
283
93
. .
31.
Bellien
J
,
Freguin-Bouilland
C
,
Joannides
R
,
Hanoy
M
,
Remy-Jouet
I
,
Monteil
C
, 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
(
2
):
414
22
. .
32.
Jia
P
,
Jin
W
,
Teng
J
,
Zhang
H
,
Zou
J
,
Liu
Z
, et al
.
Acute effects of hemodiafiltration versus conventional hemodialysis on endothelial function and inflammation: a randomized crossover study
.
Medicine
.
2016
;
95
(
16
):
e3440
. .
33.
Tousoulis
D
,
Kampoli
AM
,
Tentolouris
C
,
Papageorgiou
N
,
Stefanadis
C
,
Papageorgiou
NS
.
The role of nitric oxide on endothelial function
.
Curr Vasc Pharmacol
.
2012
;
10
(
1
):
4
18
. .
34.
Ağbaş
A
,
Canpolat
N
,
Caliskan
S
,
Yilmaz
A
,
Ekmekçi
H
,
Mayes
M
, et al
.
Hemodiafiltration is associated with reduced inflammation, oxidative stress and improved endothelial risk profile compared to high-flux hemodialysis in children
.
PLoS One
.
2018
;
13
(
6
):
e0198320
. .
35.
Zickler
D
,
Schindler
R
,
Willy
K
,
Martus
P
,
Pawlak
M
,
Storr
M
, et al
.
Medium cut-off (MCO) membranes reduce inflammation in chronic dialysis patients-A randomized controlled clinical trial
.
PLoS One
.
2017
;
12
(
1
):
e0169024
. .
36.
Catar
R
,
Moll
G
,
Kamhieh-Milz
J
,
Luecht
C
,
Chen
L
,
Zhao
H
, et al
.
Expanded hemodialysis therapy ameliorates uremia-induced systemic microinflammation and endothelial dysfunction by modulating VEGF, TNF-α and AP-1 signaling
.
Front Immunol
.
2021
;
12
:
12
. .
37.
Sevinc
M
,
Hasbal
NB
,
Yilmaz
V
,
Basturk
T
,
Ahbap
E
,
Sakaci
T
, et al
.
Comparison of circulating levels of uremic toxins in hemodialysis patients treated with medium cut-off membranes and high-flux membranes: theranova in sisli hamidiye etfal (THE SHE) randomized control study
.
Blood Purif
.
2020
;
49
(
6
):
733
42
. .
38.
Yeter
HH
,
Korucu
B
,
Akcay
OF
,
Derici
K
,
Derici
U
,
Arinsoy
T
.
Effects of medium cut-off dialysis membranes on inflammation and oxidative stress in patients on maintenance hemodialysis
.
Int Urol Nephrol
.
2020
;
52
(
9
):
1779
89
. .
39.
Kendrick
J
,
Shah
PB
,
Andrews
E
,
You
Z
,
Nowak
KJ
,
Pasch
A
, et al
.
Effect of treatment of metabolic acidosis on vascular endothelial function in patients with CKD: a pilot randomized cross-over study
.
Clin J Am Soc Nephrol
.
2018
;
13
(
10
):
1463
70
. .
40.
Jourde-Chiche
N
,
Fakhouri
F
,
Dou
L
,
Bellien
J
,
Burtey
S
,
Frimat
M
, et al
.
Endothelium structure and function in kidney health and disease
.
Nat Rev Nephrol
.
2019
;
15
(
2
):
87
108
. .
41.
Silva
IVG
,
de Figueiredo
RC
,
de Figueiredo
RC
,
de Figueiredo
RC
,
Rios
DRA
.
Effect of different classes of antihypertensive drugs on endothelial function and inflammation
.
Int J Mol Sci
.
2019
;
20
(
14
):
3458
. .
You do not currently have access to this content.