Transferrin changes in haemodialysed patients
Dorota Formanowicz
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1
2
Piotr Formanowicz
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2
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P. Formanowicz Institute of Bioorganic Chemistry, Polish Academy of Sciences
, Noskowskiego 12/14, 61-704 Poznan,
Poland
1
P. Formanowicz Institute of Computing Science, Poznan University of Technology
, Piotrowo 2, 60-965 Poznan,
Poland
2
D. Formanowicz (&) Department of Clinical Biochemistry, Poznan University of Medical Sciences
, Grunwaldzka 6, 60-780 Poznan,
Poland
Transferrin (Tf) is a glycoprotein responsible for iron transport in the human body. Physiologically in reaction with Concanavalin A, Tf occurs in four distinct variants Tf1, Tf2, Tf3 (apo-Tf) and Tf4. It was reported recently that Tf is changing, particularly during acute phase response, taking place among others in end-stage renal disease. In this study, we wanted to find the answer to three main questions: firstly, how Tf is changing in patients treated with maintenance haemodialysis (mHD), secondly, whether there are any Tf changes in the course of mHD treatment, and thirdly, what factors can affect Tf microheterogeneity in these patients. Studies were performed on 80 haemodialysed patients and 21 healthy volunteers. The Tf concentration was determined by the rocket immunoelectrophoresis, and its microheterogeneity was assessed by the ConA crossed immunoaffinity electrophoresis. During the annual observation of the distribution of the Tf variants, we have found both changes of the percentage contents of all Tf variants in the whole Tf concentration and a significant decrease in Tf2, Tf3 and Tf4 serum concentrations. Moreover, we found that decrease in the renal function, duration of mHD, and inflammation may contribute to these above-mentioned changes, which are probably the factors that should be taken into account when explaining the mechanisms of persistence of anaemia in haemodialysed patients.
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Anaemia is very common in patients with chronic
kidney disease (CKD). Factors likely contributing to
anaemia in CKD include blood loss, shortened red
cell life span, vitamin deficiencies, the uremic
milieu (a term that attempts to explain the multiple
organ dysfunction of CKD), erythropoietin (EPO)
deficiency, iron deficiency, and inflammation. Much
is known about the participation of the
abovementioned factors in anaemia, but this knowledge is
still incomplete. One of the not-yet-fully-explained
disturbances is that of iron balance in CKD. The
process of human body iron homoeostasis is a very
complex issue, and its main part was described in
detail by Formanowicz et al. [1], Sackmann et al. [2],
and Formanowicz et al. [3].
Not fully understood and explained phenomenon
of persistent anaemia and especially unexplained iron
balance disturbances in patients with CKD has
become the reason for the design of this study.
It should be noticed that, in CKD, the ability to
provide enough iron for erythropoiesis is disrupted at
several points in the body iron cycle. One of these
points is iron transport. The protein responsible for
this transport is transferrin (Tf). For reasons not yet
fully explained, Tf levels in CKD are one-half to
onethird of normal levels, diminishing the capacity of the
iron-transporting system. This situation is then
aggravated by the well-known inability to release stored
iron from macrophages, scavenging iron from
senescent red blood cells and from hepatocytes in CKD [4].
There are two main reasons for which this study
focused on the changes in Tf in CKD. First, we know
little about these changes in CKD. Second, in CKD
several factors exist, like inflammatory process and
malnutrition, which may contribute to the Tf changes.
In this part of the work, to understand the
qualitative changes of Tf, its chemical structure and
variability will be presented. Tf (79.57 kDa) consists
of three substructural domains: a single polypeptide
chain, arranged in two lobes, representing the
Nterminal and C-terminal halves of the molecule [5],
two independent, structurally similar but functionally
distinct iron-binding sites and usually two N-linked
complex glycan chains. It should be noticed that the
oligosaccharide chains are usually composed of a
common pentasaccharide core and various quantity of
sialic acid residues, galactose and/or fucose
molecules and N-acetylglucosamine, creating the
antennary chains. They differ also in the degree of
branching (antennarity), where to the most basic
biantennary structure additional antenna may be
bound, producing tri-, tetra- or even more antennary
glycans [6, 7].
A schematic representation of the transferrin
molecule is shown in Fig. 1.
The heterogeneity of N-glycan chains, varying iron
load (depending on iron supply) and modification of
the polypeptide chain (Tf variants) create a distinct Tf
microheterogeneity [8]. If the Tf molecules contain
oligosaccharides of different structures, this
phenomenon is known as a major microheterogeneity [9];
in turn, the difference in the quantity and quality of
Fig. 1 Schematic representation of the transf (...truncated)