title: The role of renal function loss on circadian misalignment of cytokines EPO, IGF-1, IL-6 and TNF-alfa in chronic renal disease.
abstract: OBJECTIVE
  Chronic inflammation plays a pivotal role in the development of renal disease. Circadian sleep-wake rhythm is disturbed in renal disease. Awareness of other disturbed rhythms, such as inflammation processes, can affect the treatment of patients with renal disease. Knowledge of possibly related circadian misalignment of the cytokines erythropoietin (EPO), Insulin Growth Factor-1 (IGF-1) and interleukins (IL) however is limited. We therefore performed an observational study. The objective of this study was to characterize levels of EPO, IGF-1 and inflammation markers IL-6 and TNF-α, related to renal function.
  
  
  METHODS
  The study population consisted of patients with various degrees of renal function, admitted to our hospital. During 24 hours, blood of 28 subjects with various degrees of renal function was collected every 2 hours. The patients were stable, not acutely ill and they were waiting for a procedure, such as elective surgery. Circadian parameters of EPO, IGF-1, IL-6 and TNF-α were measured in serum and were correlated with glomerular filtration rate (GFR) and Hb, using Pearson correlations.
  
  
  RESULTS
  Although diurnal variations in EPO level were found in 15 out of 28 patients, the curves did not show a consistent phase. The presence of an EPO rhythm was not related to GFR. No diurnal rhythm could be detected for IGF-1, IL-6 and TNF-α. Mean levels of IGF-1 were correlated inversely to mean levels of EPO (p=0.03). When divided based on GFR and Hb subjects with GFR 10-30 ml/min and lower Hb had the highest IGF-1 levels (p=0.02). A relationship between Il-6, TNF-α and EPO or GFR was not found.
  
  
  CONCLUSIONS
  The existence of a circadian (mis)alignment of EPO, IGF-1, IL-6 and TNF-α was not found. The association between high IGF-1 and low Hb suggests that EPO and IGF-1 have an alternating role, dependent on GFR, in stimulating erythropoiesis. These results could have consequences for the treatment of anemia.
authors.affiliation: Department of Internal Medicine, Meander MC, Amersfoort, the Netherlands.
authors.forename: Karien
authors.initials: K
authors.lastname: van der Putten
authors.forename: Birgit
authors.initials: B
authors.lastname: Koch
authors.forename: Eus
authors.initials: E
authors.lastname: van Someren
authors.forename: Jos
authors.initials: J
authors.lastname: Wielders
authors.forename: Piet
authors.initials: P
authors.lastname: Ter Wee
authors.forename: Elsbeth
authors.initials: E
authors.lastname: Nagtegaal
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaillard
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D002940:Circadian Rhythm / Q000502:physiology*; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood*; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000097:blood* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D007334:Insulin-Like Growth Factor I