Transferrin changes in haemodialysed patients

International Urology and Nephrology, Jun 2012

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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Transferrin changes in haemodialysed patients

Dorota Formanowicz 0 1 2 Piotr Formanowicz 0 1 2 0 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. - 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)


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Dorota Formanowicz, Piotr Formanowicz. Transferrin changes in haemodialysed patients, International Urology and Nephrology, 2012, pp. 907-919, Volume 44, Issue 3, DOI: 10.1007/s11255-011-9947-4