title: Effects of Direct Renin Blockade on Renal & Systemic Hemodynamics and on RAAS Activity, in Weight Excess and Hypertension: A Randomized Clinical Trial.
abstract: OBJECTIVE
  The combination of weight excess and hypertension significantly contributes to cardiovascular risk and progressive kidney damage. An unfavorable renal hemodynamic profile is thought to contribute to this increased risk and may be ameliorated by direct renin inhibition (DRI). The aim of this trial was to assess the effect of DRI on renal and systemic hemodynamics and on RAAS activity, in men with weight excess and hypertension.
  
  
  METHODS
  A randomized, double-blind, cross-over clinical trial to determine the effect of DRI (aliskiren 300 mg/day), with angiotensin converting enzyme inhibition (ACEi; ramipril 10 mg/day) as a positive control, on renal and systemic hemodynamics, and on RAAS activity (n = 15).
  
  
  RESULTS
  Mean (SEM) Glomerular filtration rate (101 (5) mL/min/1.73m2) remained unaffected by DRI or ACEi. Effective renal plasma flow (ERPF; 301 (14) mL/min/1.73m2) was increased in response to DRI (320 (14) mL/min/1.73m2, P = 0.012) and ACEi (317 (15) mL/min/1.73m2, P = 0.045). Filtration fraction (FF; 34 (0.8)%) was reduced by DRI only (32 (0.7)%, P = 0.044). Mean arterial pressure (109 (2) mmHg) was reduced by DRI (101 (2) mmHg, P = 0.008) and ACEi (103 (3) mmHg, P = 0.037). RAAS activity was reduced by DRI and ACEi. Albuminuria (20 [9-42] mg/d) was reduced by DRI only (12 [5-28] mg/d, P = 0.030).
  
  
  CONCLUSIONS
  In men with weight excess and hypertension, DRI and ACEi improved renal and systemic hemodynamics. Both DRI and ACEi reduced RAAS activity. Thus, DRI provides effective treatment in weight excess and hypertension.
  
  
  BACKGROUND
  Dutch trial register, registration number: 2532 www.trialregister.nl.
authors.affiliation: Department of Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Kwakernaak
authors.affiliation: Department of Medicine, Division of Vascular Medicine and Pharmacology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: L C
authors.initials: LC
authors.lastname: Roksnoer
authors.affiliation: Department of Clinical Pharmacology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lambers Heerspink
authors.affiliation: Department of Medicine, Division of Vascular Medicine and Pharmacology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: van den Berg-Garrelds
authors.affiliation: General Practitioner Practice Gorecht, Hoogezand, The Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: Lochorn
authors.affiliation: General Practitioner Practice Boterdiep, Groningen, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: van Embden Andres
authors.affiliation: General Practitioner Practice Boterdiep, Groningen, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Klijn
authors.affiliation: Department of Pharmacology, Kagawa University, School of Medicine, Miki, Kita District, Kagawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kobori
authors.affiliation: Department of Medicine, Division of Vascular Medicine and Pharmacology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: A H J
authors.initials: AH
authors.lastname: Danser
authors.affiliation: Department of Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands.|Department of Internal Medicine, Division of Nephrology, ZGT Hospital Almelo, Netherlands.
authors.forename: G D
authors.initials: GD
authors.lastname: Laverman
authors.affiliation: Department of Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Navis
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018660:Blood Pressure Monitoring, Ambulatory; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000150:complications* / Q000503:physiopathology; D017257:Ramipril / Q000494:pharmacology / Q000627:therapeutic use; D012079:Renal Circulation / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005650:Fumarates; D017257:Ramipril; D000092502:Renin Inhibitors; C446481:aliskiren