title: Effects of direct renin inhibition versus angiotensin II receptor blockade on angiotensin profiles in non-diabetic chronic kidney disease.
abstract: Direct renin inhibition (DRI) is clinically inferior to other blockers of the renin-angiotensin system (RAS). Thus far, the underlying molecular causes of this finding remain unknown.
  
  
  
  Twenty four patients with non-diabetic chronic kidney disease (CKD) stages III-IV and albuminuria were randomized to DRI or angiotensin receptor blocker (ARB). Employing a novel mass-spectrometry method, the concentrations of renin, aldosterone and plasma angiotensin peptides [Ang I, Ang II, Ang-(1-7), Ang-(1-5), Ang-(2-8), Ang-(3-8)] were quantified before and after an 8-week treatment.
  
  
  
  While blood pressure, renal function and albuminuria decreased comparably in both groups, profound RAS component differences were observed: DRI led to a massive renin increase, while suppressing both vasoconstrictive (Ang I and Ang II) and vasodilatory RAS metabolites (Ang-(1-7) and Ang-(1-5)). In contrast, ARB led to a four-fold increase of Ang I and Ang II, while Ang-(1-7) and Ang-(1-5) increased moderately but significantly. With ARB treatment, a decreased aldosterone-to-Ang II ratio suggested efficacy in blocking AT1 receptor.
  
  
  
  DRI therapy abolishes all RAS effector peptides. ARB increases both vasoconstrictive and vasodilative angiotensins, while this is accompanied by efficient blockade of vasoconstrictive effects. These differential molecular regulations should be considered when selecting optimal antihypertensive and disease-modifying therapy in CKD patients. Key messages Direct renin inhibition leads to a complete and lasting abolition of both classical and alternative RAS components. Angiotensin receptor blockade leads to effective receptor blockade and up-regulation of alternative RAS components. Differential molecular regulations of the RAS should be considered when selecting optimal antihypertensive and disease-modifying therapy in CKD patients.
authors.affiliation: a 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: a Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis , Medical University of Vienna , Vienna , Austria.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bernhofer
authors.affiliation: a 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: a 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: a 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: a 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: b Attoquant Diagnostics , Vienna , Austria.
authors.forename: Marko
authors.initials: M
authors.lastname: Poglitsch
authors.affiliation: a Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis , Medical University of Vienna , Vienna , Austria.|c Department of Internal Medicine VI, Division of Nephrology , Wilhelminenspital , Vienna , Austria.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Säemann
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000209:etiology / Q000378:metabolism; D000450:Aldosterone / Q000032:analysis; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000809:Angiotensins / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000494:pharmacology*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D012083:Renin / Q000032:analysis; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000809:Angiotensins; D009842:Oligopeptides; D010446:Peptide Fragments; D011480:Protease Inhibitors; D000450:Aldosterone; C027509:renin inhibitory peptide; D012083:Renin
keywords: Aliskiren; blood pressure; candesartan; chronic kidney disease; proteinuria; renin–angiotensin system