title: Changes in Plasma Copeptin Levels during Hemodialysis: Are the Physiological Stimuli Active in Hemodialysis Patients?
abstract: OBJECTIVE
  Plasma levels of copeptin, a surrogate marker for the vasoconstrictor hormone arginine vasopressin (AVP), are increased in hemodialysis patients. Presently, it is unknown what drives copeptin levels in hemodialysis patients. We investigated whether the established physiological stimuli for copeptin release, i.e. plasma osmolality, blood volume and mean arterial pressure (MAP), are operational in hemodialysis patients.
  
  
  METHODS
  One hundred and eight prevalent, stable hemodialysis patients on a thrice-weekly dialysis schedule were studied during hemodialysis with constant ultrafiltration rate and dialysate conductivity in this observational study. Plasma levels of copeptin, sodium, MAP, and blood volume were measured before, during and after hemodialysis. Multivariate analysis was used to determine the association between copeptin (dependent variable) and the physiological stimuli plasma sodium, MAP, excess weight as well as NT-pro-BNP immediately prior to dialysis and between copeptin and changes of plasma sodium, MAP and blood volume with correction for age, sex and diabetes during dialysis treatment.
  
  
  RESULTS
  Patients were 63 ± 15.6 years old and 65% were male. Median dialysis vintage was 1.6 years (IQR 0.7-4.0). Twenty-three percent of the patients had diabetes and 82% had hypertension. Median predialysis copeptin levels were 141.5 pmol/L (IQR 91.0-244.8 pmol/L). Neither predialysis plasma sodium levels, nor NT-proBNP levels, nor MAP were associated with predialysis copeptin levels. During hemodialysis, copeptin levels rose significantly (p<0.01) to 163.0 pmol/L (96.0-296.0 pmol/L). Decreases in blood volume and MAP were associated with increases in copeptin levels during dialysis, whereas there was no significant association between the change in plasma sodium levels and the change in copeptin levels.
  
  
  CONCLUSIONS
  Plasma copeptin levels are elevated predialysis and increase further during hemodialysis. Volume stimuli, i.e. decreases in MAP and blood volume, rather than osmotic stimuli, are associated with change in copeptin levels during hemodialysis.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Esmée M
authors.initials: EM
authors.lastname: Ettema
authors.affiliation: Dialysis Center Groningen, Groningen, The Netherlands.
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuipers
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Assa
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Groen
authors.affiliation: Dialysis Center Groningen, Groningen, The Netherlands.
authors.forename: Ralf
authors.initials: R
authors.lastname: Westerhuis
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Carlo A J M
authors.initials: CA
authors.lastname: Gaillard
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Casper F M
authors.initials: CF
authors.lastname: Franssen
mesh_terms: D000368:Aged; D001794:Blood Pressure; D001810:Blood Volume; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000097:blood; D006435:Renal Dialysis; D012964:Sodium / Q000097:blood
chemical_list: D006020:Glycopeptides; D010446:Peptide Fragments; C048197:copeptins; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D012964:Sodium