Glycosylation and Characterization of Human Transferrin in an End-Stage Kidney Disease

Author:

Miljuš Goran1ORCID,Penezić Ana1ORCID,Pažitná Lucia2ORCID,Gligorijević Nikola3ORCID,Baralić Marko45ORCID,Vilotić Aleksandra6,Šunderić Miloš1ORCID,Robajac Dragana1ORCID,Dobrijević Zorana1ORCID,Katrlík Jaroslav2,Nedić Olgica1ORCID

Affiliation:

1. Institute for the Application of Nuclear Energy (INEP), Department for Metabolism, University of Belgrade, 11000 Belgrade, Serbia

2. Institute of Chemistry, Slovak Academy of Sciences, 84538 Bratislava, Slovakia

3. Institute of Chemistry, Technology and Metallurgy, Department of Chemistry, University of Belgrade, 11000 Belgrade, Serbia

4. School of Medicine, University of Belgrade, 11000 Belgrade, Serbia

5. Clinic of Nephrology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia

6. Institute for the Application of Nuclear Energy (INEP), Department for Biology of Reproduction, University of Belgrade, 11000 Belgrade, Serbia

Abstract

Chronic kidney disease (CKD) is a global health concern affecting approximately one billion individuals worldwide. End-stage kidney disease (ESKD), the most severe form of CKD, is often accompanied by anemia. Peritoneal dialysis (PD), a common treatment for ESKD, utilizes the peritoneum for solute transfer but is associated with complications including protein loss, including transferrin (Tf) a key protein involved in iron transport. This study investigated Tf characteristics in ESKD patients compared to healthy individuals using lectin microarray, spectroscopic techniques and immunocytochemical analysis to assess Tf interaction with transferrin receptors (TfRs). ESKD patients exhibited altered Tf glycosylation patterns, evidenced by significant changes in lectin reactivity compared to healthy controls. However, structural analyses revealed no significant differences in the Tf secondary or tertiary structures between the two groups. A functional analysis demonstrated comparable Tf-TfR interaction in both PD and healthy samples. Despite significant alterations in Tf glycosylation, structural integrity and Tf-TfR interaction remained preserved in PD patients. These findings suggest that while glycosylation changes may influence iron metabolism, they do not impair Tf function. The study highlights the importance of a glucose-free dialysis solutions in managing anemia exacerbation in PD patients with poorly controlled anemia, potentially offering a targeted therapeutic approach to improve patient outcomes.

Funder

Ministry of Science, Technological Development and Innovation of the Republic of Serbia

Bilateral Cooperation project with the Republic of Slovakia

Publisher

MDPI AG

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