title: Renal hemodynamic effects of serelaxin in patients with chronic heart failure: a randomized, placebo-controlled study.
abstract: BACKGROUND
  Serelaxin is a promising therapy for acute heart failure. The renal hemodynamic effects of serelaxin in patients with chronic heart failure are unknown.
  
  
  RESULTS
  In this double-blind, randomized, placebo-controlled, multicenter study, patients with New York Heart Association Class II to III chronic heart failure, left ventricular ejection fraction ≤45%, and estimated glomerular filtration rate (GFR) 30 to 89 mL/min per 1.73 m(2) received intravenous serelaxin 30 μg/kg per day or placebo for 24 hours. Primarily, we assessed the difference between serelaxin and placebo on renal plasma flow (para-aminohippuric acid clearance) and GFR (iothalamate clearance) over 8 to 24 hours. All 22 patients from 1 clinical site were excluded from primary analyses before unblinding because of implausible measurements. The primary analysis comprised 65 patients, mean age was 68 (±10) years, 89% were male, mean estimated GFR was 64 (±19) mL/min per 1.73 m(2), and 34% had New York Heart Association Class III symptoms. Renal plasma flow increased by 29% with serelaxin and 14% with placebo (13% relative increase with serelaxin; P=0.0386), whereas GFR changes did not differ significantly during 8 to 24 hours. Filtration fraction increased by 36% with serelaxin and 62% with placebo (16% relative decrease with serelaxin; P=0.0019) during 8 to 24 hours. Changes in systolic blood pressure were largely similar, and creatinine clearance did not differ between groups. Adverse event rates were similar with serelaxin (20.5%) and placebo (25.0%).
  
  
  CONCLUSIONS
  In patients with chronic heart failure, serelaxin increased renal plasma flow and reduced the increase in filtration fraction compared with placebo, but did not affect GFR. These results suggest beneficial renal hemodynamic effects in patients with chronic heart failure.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01546532.
authors.affiliation: From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.). a.a.voors@umcg.nl.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.).
authors.forename: Marion
authors.initials: M
authors.lastname: Dahlke
authors.affiliation: From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.).
authors.forename: Sven
authors.initials: S
authors.lastname: Meyer
authors.affiliation: From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.).
authors.forename: Janina
authors.initials: J
authors.lastname: Stepinska
authors.affiliation: From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.).
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Gottlieb
authors.affiliation: From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.).
authors.forename: Andrew
authors.initials: A
authors.lastname: Jones
authors.affiliation: From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.).
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.).
authors.forename: Didier
authors.initials: D
authors.lastname: Laurent
authors.affiliation: From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.).
authors.forename: Riemer H J A
authors.initials: RH
authors.lastname: Slart
authors.affiliation: From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.).
authors.forename: Gerjan J
authors.initials: GJ
authors.lastname: Navis
mesh_terms: D000368:Aged; D003404:Creatinine / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012065:Relaxin / Q000494:pharmacology*; D010130:p-Aminohippuric Acid / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; C577649:serelaxin protein, human; D012065:Relaxin; D003404:Creatinine; D010130:p-Aminohippuric Acid
keywords: clinical trial; heart failure; hemodynamics; kidney