Astrid D H Brys1, Enrico Di Stasio2, Bert Lenaert3, Maurizio Sanguinetti4, Anna Picca5, Riccardo Calvani5, Emanuele Marzetti5, Giovanni Gambaro6, Maurizio Bossola7. 1. Divisione di Nefrologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Università Cattolica del Sacro Cuore, Roma, Italy; School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands. Electronic address: astrid.brys@unicatt.it. 2. Università Cattolica del Sacro Cuore, Roma, Italy; UOC Chimica, Biochimica e Biologia Molecolare Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. 3. School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands. 4. Divisione di Microbiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. 5. Università Cattolica del Sacro Cuore, Roma, Italy; Divisione di Geriatria, Neuroscienza e Ortopedia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. 6. Divisione di Nefrologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Università Cattolica del Sacro Cuore, Roma, Italy; Division of Nephrology, University Hospital of Verona, Verona, Italy. 7. Università Cattolica del Sacro Cuore, Roma, Italy; Haemodialysis Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.
Abstract
BACKGROUND: Little is known about the underlying aetiology of fatigue in haemodialysis (HD) patients apart from a significant association and overlapping symptomatology with depressive symptoms. Growing evidence exists for the involvement of the immune system, by pro-inflammatory cytokines, in the development of fatigue in other inflammatory diseases. In HD patients, increased exposure to bacterial endotoxins may contribute to an inflammatory response and may potentially lead to fatigue. We therefore aimed (i) to assess the interrelationship between serum endotoxin (EA) levels, interleukin-6 (IL-6) levels and fatigue in HD patients; (ii) to evaluate whether there is a relationship between depressive symptoms and inflammation as well and (iii) to what extent depressive symptoms and fatigue are related to each other. METHODS: Fatigue and depressive symptoms in daily life were assessed in 59 individuals using the SF-36 vitality subscale and the Geriatric Depression Scale. Blood samples were collected on a mid-week dialysis session to determine EA levels, through the Endotoxin Activity Assay (EAA™), and IL-6 concentrations, through the commercially available Abcam ELISA (Enzyme-Linked Immunosorbent Assay) kit. RESULTS: EA, IL-6 levels and depressive symptoms were significantly correlated with fatigue. EA levels and depressive symptoms were significant predictors of fatigue, explaining 31% of its variance. However, EA and IL-6 were not significantly associated with depression. CONCLUSIONS: Fatigue in HD patients may be related to endotoxemia and inflammation through IL-6. Furthermore, fatigue is significantly associated with depressive symptoms. Future research into the causal interrelationship of inflammation, fatigue and depression in HD patients might lead to potential targets for therapeutic strategies.
BACKGROUND: Little is known about the underlying aetiology of fatigue in haemodialysis (HD) patients apart from a significant association and overlapping symptomatology with depressive symptoms. Growing evidence exists for the involvement of the immune system, by pro-inflammatory cytokines, in the development of fatigue in other inflammatory diseases. In HD patients, increased exposure to bacterial endotoxins may contribute to an inflammatory response and may potentially lead to fatigue. We therefore aimed (i) to assess the interrelationship between serum endotoxin (EA) levels, interleukin-6 (IL-6) levels and fatigue in HD patients; (ii) to evaluate whether there is a relationship between depressive symptoms and inflammation as well and (iii) to what extent depressive symptoms and fatigue are related to each other. METHODS:Fatigue and depressive symptoms in daily life were assessed in 59 individuals using the SF-36 vitality subscale and the Geriatric Depression Scale. Blood samples were collected on a mid-week dialysis session to determine EA levels, through the Endotoxin Activity Assay (EAA™), and IL-6 concentrations, through the commercially available Abcam ELISA (Enzyme-Linked Immunosorbent Assay) kit. RESULTS: EA, IL-6 levels and depressive symptoms were significantly correlated with fatigue. EA levels and depressive symptoms were significant predictors of fatigue, explaining 31% of its variance. However, EA and IL-6 were not significantly associated with depression. CONCLUSIONS:Fatigue in HD patients may be related to endotoxemia and inflammation through IL-6. Furthermore, fatigue is significantly associated with depressive symptoms. Future research into the causal interrelationship of inflammation, fatigue and depression in HD patients might lead to potential targets for therapeutic strategies.