Blood–Brain Barrier Biomarkers before and after Kidney Transplantation

Author:

Hernandez Leah1ORCID,Ward Liam J.12ORCID,Arefin Samsul1ORCID,Barany Peter1,Wennberg Lars3,Söderberg Magnus4ORCID,Bruno Stefania5ORCID,Cantaluppi Vincenzo6ORCID,Stenvinkel Peter1ORCID,Kublickiene Karolina1ORCID

Affiliation:

1. Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, 171 77 Stockholm, Sweden

2. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 587 58 Linköping, Sweden

3. Department of Transplantation Surgery, Karolinska University Hospital, 141 86 Stockholm, Sweden

4. Department of Pathology, Clinical Pharmacology and Safety Sciences, R&D AstraZeneca, 431 83 Gothenburg, Sweden

5. Department of Medical Sciences, University of Torino, 10124 Torino, Italy

6. Nephrology and Kidney Transplant Unit, Department of Translational Medicine (DIMET), University of Piemonte Orientale (UPO), “Maggiore della Carita” University Hospital, 28100 Novara, Italy

Abstract

Kidney transplantation (KT) may improve the neurological status of chronic kidney disease (CKD) patients, reflected by the altered levels of circulating BBB-specific biomarkers. This study compares the levels of neuron specific enolase (NSE), brain-derived neurotrophic factor (BDNF), neurofilament light chain (NfL), and circulating plasma extracellular vesicles (EVs) in kidney-failure patients before KT and at a two-year follow up. Using ELISA, NSE, BDNF, and NfL levels were measured in the plasma of 74 living-donor KT patients. Plasma EVs were isolated with ultracentrifugation, and characterized for concentration/size and surface protein expression using flow cytometry from a subset of 25 patients. Lower NSE levels, and higher BDNF and NfL were observed at the two-year follow-up compared to the baseline (p < 0.05). Male patients had significantly higher BDNF levels compared to those of females. BBB biomarkers correlated with the baseline lipid profile and with glucose, vitamin D, and inflammation markers after KT. BBB surrogate marker changes in the microcirculation of early vascular aging phenotype patients with calcification and/or fibrosis were observed only in NSE and BDNF. CD31+ microparticles from endothelial cells expressing inflammatory markers such as CD40 and integrins were significantly reduced after KT. KT may, thus, improve the neurological status of CKD patients, as reflected by changes in BBB-specific biomarkers.

Funder

CIMED, Heart and Lung Foundation, Westman and Swedish Medical Research Council; GENDER-NET Plus ERA-NET Initiative

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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