1 3
Int Urol Nephrol
DOI 10.1007/s11255-015-1114-x
NEPHROLOGY - ORIGINAL ARTICLE
The association of high sCD163/sTWEAK ratio
with cardiovascular disease in hemodialysis patients
Crina Claudia Rusu
1
· Simona Racasan
2
· Ina Maria Kacso
1
· Liviu Ghervan
3
·
Diana Moldovan
1
· Alina Potra
1
· Ioan Mihai Patiu
2
· Cosmina Bondor
4
·
Mirela Gherman Caprioara
1
Received: 29 July 2015 / Accepted: 14 September 2015
© Springer Science+Business Media Dordrecht 2015
multivariate analysis, only logarithm of sCD163/sTWEAK
ratio (p = 0.04) and smoking (p = 0.03) was significantly
associated with CVD. The levels of these molecules and
their ratio were correlated with atherosclerosis risk fac-
tors: diabetes mellitus, high fasting glucose, tricipital skin-
fold thickness and CRP as well as (for sCD163/sTWEAK)
intravenous iron therapy.
Conclusions Cardiovascular disease is associated with
increased sCD163/sTWEAK ratio. To our knowledge, this
is the first report about this relationship in HD patients.
Keywords sCD163/sTWEAK ratio · Hemodialysis ·
Cardiovascular disease · Atherosclerosis
Introduction
Chronic kidney disease patients (CKD) have a markedly
increased mortality rate, mainly due to cardiovascular dis-
ease (CVD). New biomarkers emerge in the search for
early diagnosis tools and targeted prophylactic treatments.
Among the molecules proposed as CV risk biomarkers in
patients with and without CKD are tumor necrosis factor
(TNF)-like weak inducer of apoptosis (TWEAK), a mem-
ber of the TNF superfamily that is synthesized as a type II
transmembrane glycoprotein and circulates in plasma as a
soluble form (sTWEAK) [1], and its scavenger CD163 [2].
TWEAK gene is expressed in many tissues, includ-
ing healthy vasculature, and the molecule exerts specific
biological effects after binding to its receptor, fibroblast
growth factor-inducible 14 (Fn14) [3, 4]. Fn14 expression
is low or undetectable in healthy tissues and is upregulated
in context of disease such as the arterial wall in atheroscle-
rosis [5]. sTWEAK induces various and sometimes contra-
dictory effects depending on cell type, cell cycle and the
Abstract
Purpose Cardiovascular disease (CVD) is the most com-
mon cause of death in hemodialysis (HD) patients. Trans-
membrane proteins that circulate as soluble form such as
tumor necrosis factor (TNF)-like weak inducer of apop-
tosis (TWEAK) and CD163 have been proposed in previ-
ous studies as CVD biomarkers in chronic kidney disease
patients. In HD patients, since studies are scarce, the role of
these proteins is not completely understood. We tested the
hypothesis that sTWEAK, sCD163 or sCD163/sTWEAK
ratio could be associated with cardiovascular disease in HD
patients.
Methods We recorded current clinical and biological data,
and we measured sTWEAK and sCD163 serum levels by
ELISA in 70 hemodialysis patients. Univariate analysis
and multivariate (logistic regression) analysis were used
to identify the relation between sTWEAK, sCD163 and
sCD163/sTWEAK ratio and CVD.
Results In univariate analysis, CVD in HD patients is
associated with higher sCD163/sTWEAK ratio (p = 0.04),
sCD163 (p = 0.07), CRP (p = 0.04), age (p = 0.07), smok-
ing (p = 0.09) and vascular calcifications (p = 0.10). In
* Crina Claudia Rusu
crinaclaudiarusu@yahoo.ro
1
Department of Nephrology, University of Medicine
and Pharmacy “Iuliu Hatieganu” Cluj, 3-5 Clinicilor Street,
400006 Cluj-Napoca, Romania
2
Nefromed Dialysis Center, 40 Ana Aslan Street,
Cluj-Napoca, Romania
3
Institute of Clinical Urology and Renal Transplantation,
4-6 Clinicilor Street, 400006 Cluj-Napoca, Romania
4
Department of Informatics and Biostatistics, University
of Medicine and Pharmacy “Iuliu Hatieganu” Cluj,
6 Pasteur Street, 400349 Cluj-Napoca, Romania