Lymphocyte Phenotypes and Protein-Bound Uremic Toxins as Determinants of Clinical Outcomes in Hemodialysis Patients

Background/Objectives: The impact of protein bound uremic toxins (PBUT) and lymphocyte alterations in morbidity and mortality in patients on hemodialysis (HD) is of great concern. Aim of this study was the assessment of association between PBUT, immunosenescencent lymphocytes’ phenotype and clinical events [cardiovascular, severe infections (hospitalization due to infection, respiratory infection), all-cause mortality] during 2-year follow-up. Methods: In this prospective observational study, lymphocytes’ phenotype of 54 patients on HD and 31 age-matched controls, was analyzed by flow cytometry, and simultaneously, PBUT serum levels [hippuric acid (HA), indoxyl sulfate (IxS), p-cresyl sulfate (pCS), p-cresyl glycuronide (pCG), in-dole-3-acetic acid (IAA), 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)] were quantified by ultra-performance liquid chromatography. Results: Patients with increased levels of free IxS, total and free HA had higher mortality within 2-year follow-up period (p = 0.049, p = 0.01, p = 0.01, respectively). In patients who experienced cardio-vascular events, higher concentrations of CMPF (p=0.015) were observed. Higher total and free HA levels associate with increased all-cause mortality in patients on HD, independently of age, dialysis vintage, decreased count of CD4+CD45RA+CD31+ and naïve B cells (CD19+IgD+CD27-). Conclusions: In patients on HD, increased levels of total and free HA associate with an increased risk of death.