title: Angiotensin blockade and progressive loss of kidney function in hemodialysis patients: a randomized controlled trial.
abstract: BACKGROUND
  Glomerular filtration rate (GFR) declines during long-term dialysis treatment. In peritoneal dialysis, blockade of the renin-angiotensin-aldosterone system reduces GFR decline. Observational studies suggest that similar treatment may preserve kidney function in hemodialysis (HD).
  
  
  METHODS
  A multicenter, randomized, placebo-controlled, double-blinded trial, with 1-year follow-up.
  
  
  METHODS
  Adult HD patients with urine output >300mL/24h, HD vintage less than 1 year, and cardiac ejection fraction >30%. Patients were included from 6 HD centers.
  
  
  METHODS
  Patients were randomly assigned to placebo or the angiotensin II receptor blocker irbesartan, 300mg daily. Target systolic blood pressure (BP) was 140mm Hg.
  
  
  METHODS
  Primary outcomes were change in GFR measured as the mean of creatinine and urea renal clearance together with urine volume. Secondary outcomes were change in albuminuria, renin-angiotensin II-aldosterone hormone plasma levels, and time to anuria.
  
  
  RESULTS
  Of 82 patients randomly assigned (41 patients in each group), 56 completed 1 year of treatment. The placebo and irbesartan groups were comparable at baseline in terms of sex balance (26 vs 30 men), mean age (62 vs 61 years), median HD vintage (137 vs 148 days), mean HD time (10 vs 11h/wk), median urine volume (1.19 vs 1.26L/d), and mean GFR (4.8 vs 5.7mL/min/1.73m(2)). The target BP level was reached in both groups and BP did not differ significantly between groups over time. Adverse-event rates were similar. GFR declined by a mean of 1.7 (95% CI, 1.2-2.3) and 1.8 (95% CI, 1.1-2.4) mL/min/1.73m(2) per year in the placebo and irbesartan groups, respectively. Mean difference (baseline values minus value at 12 months) between groups was -0.0 (95% CI, -0.8 to 0.8). In each group, 4 patients became anuric.
  
  
  CONCLUSIONS
  GFR decline rates were lower than expected, reducing the power.
  
  
  CONCLUSIONS
  At equal BP levels, we found that irbesartan treatment did not affect the decline in GFR or urine volume significantly during 1 year of treatment in HD patients. Irbesartan treatment was used safely in the studied population.
authors.affiliation: Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: krista@ki.au.dk.
authors.forename: Krista Dybtved
authors.initials: KD
authors.lastname: Kjaergaard
authors.affiliation: Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Christian Daugaard
authors.initials: CD
authors.lastname: Peters
authors.affiliation: Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Jespersen
authors.affiliation: Department of Internal Medicine, Regional Hospital Viborg, Viborg, Denmark.
authors.forename: Ida Nørager
authors.initials: IN
authors.lastname: Tietze
authors.affiliation: Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jens Kristian
authors.initials: JK
authors.lastname: Madsen
authors.affiliation: Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Birgitte Bang
authors.initials: BB
authors.lastname: Pedersen
authors.affiliation: Department of Medicine, Fredericia Hospital, Fredericia, Denmark.
authors.forename: Marija Kristina
authors.initials: MK
authors.lastname: Novosel
authors.affiliation: Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Kathrine Skaaning
authors.initials: KS
authors.lastname: Laursen
authors.affiliation: Department of Public Health, Institute of Biostatistics, Aarhus University, Aarhus, Denmark.
authors.forename: Bo Martin
authors.initials: BM
authors.lastname: Bibby
authors.affiliation: Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Strandhave
authors.affiliation: Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Jens Dam
authors.initials: JD
authors.lastname: Jensen
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000809:Angiotensins / Q000037:antagonists & inhibitors* / Q000502:physiology; D001713:Biphenyl Compounds / Q000627:therapeutic use; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects / Q000639:trends*; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology / Q000628:therapy*; D013777:Tetrazoles / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000809:Angiotensins; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan
keywords: Adult; GFR decline; SAFIR (Saving Residual Renal Function in Hemodialysis Patients Receiving Irbesartan) trial; albuminuria; aldosterone; angiotensin II; angiotensin II receptor blocker; anuria; double-blinded; glomerular filtration rate (GFR); hemodialysis (HD); investigator-initiated; irbesartan; multicenter study; placebo; preservation of residual renal function; randomized controlled trial; renin; residual renal function; urine volume