title: Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction).
abstract: OBJECTIVE
  We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals.
  
  
  RESULTS
  Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007).
  
  
  CONCLUSIONS
  Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction.
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schroten
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Kevin
authors.initials: K
authors.lastname: Damman
authors.affiliation: Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, Netherlands.
authors.forename: Marc H
authors.initials: MH
authors.lastname: Hemmelder
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: University of Groningen, Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.affiliation: University of Groningen, Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Carlo A J M
authors.initials: CA
authors.lastname: Gaillard
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Wiek H
authors.initials: WH
authors.lastname: Van Gilst
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands. Electronic address: H.Hillege@umcg.nl.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
mesh_terms: D000368:Aged; D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D013318:Stroke Volume; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D005650:Fumarates; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren