title: Reversibility of the effects of aliskiren in the renal versus systemic circulation.
abstract: OBJECTIVE
  Renal hemodynamic effects of inhibitors of the renin-angiotensin system can increase the risk of acute kidney injury under certain conditions. The BP-lowering effects of the renin inhibitor aliskiren are sustained 3-4 weeks after withdrawal. In this study, the reversibility of the renal hemodynamic effects of aliskiren was tested.
  
  
  METHODS
  In this open-label study, renal perfusion was measured by 1.5-T magnetic resonance imaging-arterial spin labeling in 34 subjects with arterial hypertension before aliskiren (pre-aliskiren), after 4 weeks of aliskiren treatment (300 mg), and 4-5 days (∼2.5-3.0× plasma half-life) after withdrawal (post-aliskiren).
  
  
  RESULTS
  Aliskiren reduced systolic BP from 152 ± 14 to 139 ± 16 mmHg (P<0.0001), which was sustained post-aliskiren (136 ± 13 mmHg, P=1.00 versus aliskiren). Aliskiren significantly altered renal perfusion (P=0.005), increasing from 272 ± 25 pre-aliskiren to 287 ± 29 ml/min per 100 g during aliskiren (P=0.03). This increase in renal perfusion was completely reversed post-aliskiren (272 ± 26 ml/min per 100 g, P=0.03 versus aliskiren, P=0.63 versus pre-aliskiren). No changes were noted in urinary angiotensinogen levels. Plasma renin activity was reduced by aliskiren, which was sustained post-aliskiren. Angiotensin II and aldosterone were reduced by aliskiren but recovered post-aliskiren to pre-aliskiren levels.
  
  
  CONCLUSIONS
  After withdrawal of aliskiren, the effects on BP were sustained, whereas increase in renal perfusion was reversed, which was associated with recovery of angiotensin II and aldosterone to pretreatment levels. Renal hemodynamic effects are more readily reversible than systemic effects of aliskiren.
authors.affiliation: Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Markus P
authors.initials: MP
authors.lastname: Schneider
authors.forename: Rolf
authors.initials: R
authors.lastname: Janka
authors.forename: Thomas
authors.initials: T
authors.lastname: Ziegler
authors.forename: Ulrike
authors.initials: U
authors.lastname: Raff
authors.forename: Martin
authors.initials: M
authors.lastname: Ritt
authors.forename: Christian
authors.initials: C
authors.lastname: Ott
authors.forename: Roland
authors.initials: R
authors.lastname: Veelken
authors.forename: Michael
authors.initials: M
authors.lastname: Uder
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000577:Amides / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000097:blood; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D005650:Fumarates / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005858:Germany; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D055420:Perfusion Imaging / Q000379:methods; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000092502:Renin Inhibitors
chemical_list: D000450:Aldosterone; D000577:Amides; D000804:Angiotensin II; D000959:Antihypertensive Agents; D005650:Fumarates; D012083:Renin; D014665:Vasodilator Agents; D000092502:Renin Inhibitors; C446481:aliskiren