Angiotensin blockade and progressive loss of kidney function in hemodialysis patients: a randomized controlled trial

Am J Kidney Dis. 2014 Dec;64(6):892-901. doi: 10.1053/j.ajkd.2014.05.011. Epub 2014 Jul 8.

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).

Study design: A multicenter, randomized, placebo-controlled, double-blinded trial, with 1-year follow-up.

Setting & participants: 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.

Intervention: Patients were randomly assigned to placebo or the angiotensin II receptor blocker irbesartan, 300mg daily. Target systolic blood pressure (BP) was 140mm Hg.

Outcomes & measurements: 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.

Limitations: 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.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensins / antagonists & inhibitors*
  • Angiotensins / physiology
  • Biphenyl Compounds / therapeutic use
  • Disease Progression*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Irbesartan
  • Kidney / drug effects
  • Kidney / physiology*
  • Male
  • Middle Aged
  • Renal Dialysis / adverse effects
  • Renal Dialysis / trends*
  • Renal Insufficiency, Chronic / physiopathology
  • Renal Insufficiency, Chronic / therapy*
  • Tetrazoles / therapeutic use

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensins
  • Biphenyl Compounds
  • Tetrazoles
  • Irbesartan