Document Detail


Reversibility of the effects of aliskiren in the renal versus systemic circulation.
MedLine Citation:
PMID:  22173856     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVES: 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.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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:
Markus P Schneider; Rolf Janka; Thomas Ziegler; Ulrike Raff; Martin Ritt; Christian Ott; Roland Veelken; Michael Uder; Roland E Schmieder
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-12-15
Journal Detail:
Title:  Clinical journal of the American Society of Nephrology : CJASN     Volume:  7     ISSN:  1555-905X     ISO Abbreviation:  Clin J Am Soc Nephrol     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-16     Completed Date:  2012-06-12     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101271570     Medline TA:  Clin J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  258-64     Citation Subset:  IM    
Affiliation:
Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Erlangen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aldosterone / blood
Amides / blood,  pharmacokinetics,  therapeutic use*
Analysis of Variance
Angiotensin II / blood
Antihypertensive Agents / blood,  pharmacokinetics,  therapeutic use*
Blood Pressure / drug effects*
Female
Fumarates / blood,  pharmacokinetics,  therapeutic use*
Germany
Half-Life
Humans
Hypertension / blood,  drug therapy*,  physiopathology
Magnetic Resonance Imaging
Male
Middle Aged
Perfusion Imaging / methods
Renal Circulation / drug effects*
Renin / antagonists & inhibitors,  blood
Renin-Angiotensin System / drug effects*
Time Factors
Treatment Outcome
Vasodilation / drug effects*
Vasodilator Agents / blood,  pharmacokinetics,  therapeutic use*
Chemical
Reg. No./Substance:
0/Amides; 0/Antihypertensive Agents; 0/Fumarates; 0/Vasodilator Agents; 11128-99-7/Angiotensin II; 502FWN4Q32/aliskiren; 52-39-1/Aldosterone; EC 3.4.23.15/Renin
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