Acute renal failure:acute tubular necrosis: anaritide had no clear effect.

Clinical bottom line (level 1b-)

  1. Patients with acute tubular necrosis who were given anaritide had no clear difference in dialysis-free survival or mortality, than those given placebo.
Allgren et al: New England Journal of Medicine 1997; 336 (12): 828-834
Expires August 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 59 clinical centres, USA and Canada

504 patients (aged mean 62 years, 66% male) critically ill patients with acute tubular necrosis due to recent ischaemic or nephrotoxic insults and an increase in serum creatinine 88 micromol/l or more over 48 hours despite optimisation of their volume status.

Excluded if
  • <18 years old
  • vascular obstruction
  • obstruction
  • systemic or intrinsic renal diseases other than acute tubular necrosis
  • dialysis during current episode of acute renal failure
  • systolic blood pressure <90 mmHg despite the use of vasopressor therapy
  • patients expected to require dialysis within 24 hours
  • not candidates for dialysis
  • underlying medical conditions of such severity that an improvement in renal function would not be expected to improve clinical outcome
  • prior renal transplantation
  • severe chronic renal insufficiency (creatinine >264 micromol/l)


    • Control Group: (n = 248, 243 analysed): placebo
    Experimental Group: (n = 256, 255 analysed): anaritide (a synthetic form of atrial natriuretic peptide) 0.05 microg/kg/min i.v. increased over the first 90 minutes to 0.20 microg/kg/min and continued at that level, or the highest dose that the patient had tolerated, for 24 hours
    Use of low dose dopamine (3 mg/kg i.v. or less( (34%) or diuretics (60%) were at the discretion of the investigator.
    99% followed for 21 days

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    dialysis-free survival 21 days 120
    (46.9%)    		 107
    (43.2%)    		 8%
    (-12% to 24%)    		 3.73%
    (-4.95% to 12.4%)    		 27
    (NNT = 8 to infinity;
    NNH = 20 to infinity)
    death 21 days 67
    (26.2%)    		 73
    (29.4%)    		 -12%
    (-49% to 15%)    		 -3.26%
    (-11.1% to 4.56%)    		 -31
    (NNT = 22 to infinity;
    NNH = 9 to infinity)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    serum creatinine (micromol/l) 265
    (194)     		248
    (177)     		17
    (-15 to 50)

    Comments

    1. At enrolment, 84% of patients were in an intensive care unit and 50% were intubated. Acute tubular necrosis was thought to be due to nephrotoxins in 22%, ischaemia in 26% and multiple causes in 51%.
    2. Subgroup analysis revealed a benefit in the group that was oliguric at baseline, and a second trial was initiated to study this group of patients. This 250 patient study was suspended following an interim analysis that showed a very low probability of a positive outcome for the primary clinical endpoint of dialysis-free survival.
    3. Current experimental therapies centre around growth-factor like substances

    Citation

    1. Allgren RL, Marbury TC, Rahman N, et al: Anaritide in acute tubular necrosis. New England Journal of Medicine 1997; 336 (12): 828-834
    Search Terms: author's files
    Contributor: Catherine Clase, Chris Ball and Clare Wotton, April 2000
    Reviewer: Mohammad Saklayen

    Clinical Question.
    Patient acute tubular necrosis
    Intervention or Exposure anaritide
    Comparison placebo
    Outcome dialysis-free survival and death