Fatigue Is Associated With Serum interleukin-6 Levels and Symptoms of Depression in Patients on Chronic Hemodialysis

J Pain Symptom Manage. 2015 Mar;49(3):578-85. doi: 10.1016/j.jpainsymman.2014.07.009. Epub 2014 Aug 15.


Context: Little is known about activated immune-inflammatory pathways and interleukin-6 (IL-6) in the development of fatigue and/or depression in patients with end-stage renal disease on chronic hemodialysis (HD).

Objectives: To evaluate the possible correlation between fatigue and serum levels of IL-6 in patients on chronic HD.

Methods: One hundred HD patients were assessed for the presence of fatigue using the SF-36 Vitality subscale and were administered the Beck Depression Inventory (BDI), the Hamilton Anxiety Rating Scale (HARS), the Mini-Mental State Examination (MMSE), the activities of daily living (ADL), and the instrumental activities of daily living (IADL). We also calculated the time of recovery after hemodialysis (TIRD) and the number/severity of comorbidities using the Charlson Comorbidity Index (CCI). Laboratory parameters were measured as well as serum IL-6.

Results: Forty-three patients constituted the fatigued group and 57 the nonfatigued group. Age, CCI, BDI, HARS, and TIRD were significantly higher in fatigued patients than in the nonfatigued patients. Conversely, the scores of ADL, IADL, and MMSE were significantly lower in fatigued than in nonfatigued patients. Serum IL-6 levels (pg/mL) were higher in the fatigued group (5.1 ± 3.4) than in the nonfatigued group (1.6 ± 1.5; P < 0.001); serum albumin and creatinine levels were significantly lower. Twenty-six patients (26%) had no symptoms of depression (BDI score <10), and 74 patients (74%) had symptoms of depression (BDI score >9). Patients with a BDI score >9 were older; had a higher CCI; a lower MMSE; a higher TIRD; lower serum albumin, creatinine, and urea levels; and higher serum IL-6 levels. The correlation analyses showed that the score of the SF-36 Vitality subscale was associated with age, dialytic age, TIRD, ADL, IADL, CCI, BDI, HARS, MMSE, serum urea, creatinine, albumin, and IL-6 levels. On multivariate general linear model analyses, with fatigue as the dependent variable and gender as a second factor, BDI and serum IL-6 levels were independently associated with the score of the SF-36 Vitality subscale. A canonical correlation analysis was performed including in the model fatigue, BDI, and biomarkers; the correlation was 0.679 (R(2) = 0.462). Fatigue, BDI, and IL-6 among biomarkers showed the strongest association with the underlying construct (standardized canonical coefficients = -0.989, 0.015, and 0.852, respectively), thus explaining a correlation of IL-6 with both depression and fatigue.

Conclusion: Fatigue was significantly associated with symptoms of depression and serum IL-6 levels in patients receiving chronic HD.

Keywords: Hemodialysis; depression; fatigue; inflammation; interleukin-6.

MeSH terms

  • Aged
  • Comorbidity
  • Cross-Sectional Studies
  • Depression / blood*
  • Depression / complications
  • Enzyme-Linked Immunosorbent Assay
  • Fatigue / blood*
  • Fatigue / complications
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / therapy*
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neuropsychological Tests
  • Psychiatric Status Rating Scales
  • Renal Dialysis*


  • IL6 protein, human
  • Interleukin-6