title: Molecular regulation of the renin-angiotensin system in haemodialysis patients.
abstract: BACKGROUND
  Blockade of the renin-angiotensin system (RAS) exerts beneficial effects in patients with mild-to-moderate chronic kidney disease, yet evidence suggesting a similar benefit in haemodialysis (HD) patients is not available. Furthermore, knowledge of the effects of RAS blockade on systemic RAS components in HD patients is limited. Analysis of the quantity and dynamics of all known peripheral constituents of the RAS may yield important pathomechanistic information of a widespread therapeutic measure in HD patients.
  
  
  METHODS
  Fifty-two HD patients from the following groups were analysed cross-sectionally: patients without RAS blockade (n = 16), angiotensin-converting enzyme inhibitor (ACEi) users (n = 8), angiotensin receptor blocker (ARB) users (n = 11), patients on ACEi plus ARB (dual blockade, n = 8) and anephric patients (n = 9). Ten healthy volunteers served as controls. Angiotensin metabolites were quantified by mass spectrometry.
  
  
  RESULTS
  In general, HD patients showed a broad variability of RAS activity. Patients without RAS blockade displayed angiotensin metabolite patterns similar to healthy controls. ACEi therapy increased plasma Ang 1-10 and Ang 1-7 concentrations, whereas ARB treatment increased both Ang 1-8 and Ang 1-5, while suppressing Ang 1-7 to minimal levels. Dual RAS blockade resulted in high levels of Ang 1-10 and suppressed levels of other angiotensins. Anephric patients were completely devoid of detectable levels of circulating angiotensins.
  
  
  CONCLUSIONS
  In HD patients, the activity status of the systemic RAS is highly distorted with the emergence of crucial angiotensin metabolites upon distinct RAS blockade. The characterization of molecular RAS patterns associated with specific RAS interfering therapies may help to individualize future clinical studies and therapies.
authors.affiliation: Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Kovarik
authors.affiliation: Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Marlies
authors.initials: M
authors.lastname: Antlanger
authors.affiliation: Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Domenig
authors.affiliation: Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Kaltenecker
authors.affiliation: Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Manfred
authors.initials: M
authors.lastname: Hecking
authors.affiliation: Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Haidinger
authors.affiliation: Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Werzowa
authors.affiliation: Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Chantal
authors.initials: C
authors.lastname: Kopecky
authors.affiliation: Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Säemann
mesh_terms: D000328:Adult; D000803:Angiotensin I / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011945:Receptors, Angiotensin / Q000187:drug effects; D006435:Renal Dialysis; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D000803:Angiotensin I
keywords: RAS blockade; angiotensins; haemodialysis