Immunosenescence and Immune Exhaustion Are Associated with Levels of Protein-Bound Uremic Toxins in Patients on Hemodialysis

Author:

Tourountzis Theodoros1ORCID,Lioulios Georgios2,Van Laecke Steven3,Ginikopoulou Evdoxia1,Nikolaidou Vasiliki4,Moysidou Eleni2ORCID,Stai Stamatia2,Christodoulou Michalis2ORCID,Fylaktou Asimina4,Glorieux Griet3ORCID,Stangou Maria2ORCID

Affiliation:

1. Protypo Dialysis Center of Thessaloniki, 55535 Thessaloniki, Greece

2. Department of Nephrology, General Hospital “Hippokratio”, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece

3. Department of Internal Medicine and Pediatrics, Nephrology Unit, Ghent University Hospital, 9000 Gent, Belgium

4. Department of Immunology, National Peripheral Histocompatibility Center, General Hospital “Hippokratio”, 54642 Thessaloniki, Greece

Abstract

Background: The accumulation of protein-bound uremic toxins (PBUTs) in chronic kidney disease may affect patients’ immune status. The aim of the study was to evaluate their potential impacts on lymphocyte alterations in patients on hemodialysis (HD). Methods: The plasma levels of PBUTs were assessed in 54 patients on HD and 31 healthy individuals, using ultra-performance liquid chromatography. The results correlated with the senescent and exhausted status of lymphocytes, based on certain surface molecules, analyzed by flow cytometry. Results: The plasma levels of PBUTs were significantly increased in the patients on HD compared with the healthy controls. The patients with residual kidney function had reduced hippuric acid (HA) levels, total (p = 0.03) and free (p = 0.04), and free IxS levels (p = 0.02). The total and free HA levels correlated negatively with less differentiated subpopulations, CD4+CD45RA+CD31+ (p = 0.037 and p = 0.027), CD8+CD28+CD57− (p = 0.01, p = 0.01), and naïve B cells (CD19+IgD+CD27−) (p = 0.04, p = 0.03). Both the total and the free pCS levels correlated positively with exhausted CD4 cells, p = 0.02 and p = 0.01, respectively. A multivariate analysis showed that IxS and age were the main independent parameters implicated in the reduction intotal CD4 and B lymphocytes and their naïve and early differentiated subsets. Conclusions: Increased PBUTs levels are associated with immune disturbances of patients on HD, HA, and IxS in the immunosenescent and pCS in the immunoexhaustion alterations.

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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