Title:A Causal-Pathway Phenotype of Chronic Fatigue Syndrome due to Hemodialysis
in Patients with End-Stage Renal Disease
Volume: 22
Issue: 2
Author(s): Halah Nori Asad, Hussein Kadhem Al-Hakeim, Shatha Rouf Moustafa and Michael Maes*
Affiliation:
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Department
of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria
- School of Medicine, IMPACT Strategic Research Centre, Deakin University, VIC, 3220, Australia
Keywords:
Myalgic Encephalomyelitis/chronic fatigue syndrome, physiological stress, inflammation, neuro-immune, oxidative stress, biomarkers.
Abstract:
Background: End-stage renal disease (ESRD) is associated with fatigue and physiosomatic
symptoms.
Objective: The objective of this study is to delineate the associations between severity of fatigue and
physio-somatic symptoms and glomerular filtration rate, inflammatory biomarkers, and Wnt/cateninpathway
proteins.
Methods: The Wnt-pathway related proteins β-catenin, Dickkopf-related protein 1 (DKK1), R-spondin-
1, and sclerostin were measured by ELISA technique in 60 ESRD patients and 30 controls. The
Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to assess the severity of FF
symptoms.
Results: ESRD is characterized by a significant increase in the total FF score, muscle tension, fatigue,
sadness, sleep disorders, gastro-intestinal (GI) symptoms, and a flu-like malaise. The total-FF score
was significantly correlated with serum levels of urea, creatinine, and copper (positively), and
β-catenin, eGFR, hemoglobin, albumin, and zinc (inversely). The total-FF score was associated with
the number of total dialysis and weekly dialysis sessions, and these dialysis characteristics were more
important in predicting FF scores than eGFR measurements. Partial Least Squares analysis showed
that the FF score comprised two factors that are differently associated with biomarkers: a) 43.0% of
the variance in fatigue, GI symptoms, muscle tension, sadness, and insomnia is explained by hemoglobin,
albumin, zinc, β-catenin, and R-spondin-1; and b) 22.3% of the variance in irritability, concentration
and memory impairments by increased copper and cations/chloride ratio, and male sex.
Conclusion: ESRD patients show high levels of fatigue and physio-somatic symptoms associated with
hemodialysis and mediated by dialysis-induced changes in inflammatory pathways, the Wnt/catenin
pathway, and copper.