Intensity of Renal Support. NIH ARF Trial Network. NEJM 2008.

Intensity of Renal Support in Critically Ill patients with Acute Kidney Injury. VA/NIH Acute Renal Failure Trial Network. N Engl J Med: May 20, 2008;359.

A copy of this paper is available as a PDF in the file box, or you can click the link above for full text.

Intro : This multicentre, non blinded RCT had 2 arms; High intensity intermittent HD (6/week) or CVVH at 35ml/kg vs low intensity intermittant HD (3/week) or CVVH at 20ml/kg. HD was used if the patient’s were heamodynamically stable (defined by cardiovascular SOFA score <2). 1124 patient’s randomised if ARF + 1 additional organ failure present (CRF excluded). Patients on low intensity treatment were permitted isolated ultra-filtration for volume overload if required . Primary end point was all cause mortality at 60 days.

Methods : Patient groups well matched, with average APACHE = 26±7. Powered for 10% difference in mortality. 60% ARF felt to be multi-factorial, and overwhelming majority ischeamic or septic. They did appear to hit the targeted treatments accurately, it appears patients received both HD and CVVH during their ICU stays in the majority of cases (this is not clear).

Results : Mortality high at 50% (as to be expected from this patient population), and not significantly different between groups. Secondary end points of days of organ support also not significant. Significantly more hypotension & electrolyte disturbance in the high intensity group.

Comment : Well conducted study which reflects US practise, less applicable to local ICUs where CVVH use is the norm although this should not detract from the results. Undermines our current stratergy which more closely mirrors the intensive arm. Although primary end point unchanged, intensive therapy may cause more complications, and is certainly harder to achieve and more costly.

Does their use of isolated ultra-filtration cause concern ? It’s difficult to see which patients recieved this therapy although total treatment numbers were low.

Should we change local practise to a lower CVVH target on the basis of this study…….?

Dan Harvey

5 comments so far

  1. akeeshan on

    Hi dan, good idea this site. Just a quick comment this study did it include sepsis? for some reason couldnt download inclusion criteria! This subgroup are probably the patients that would benefit from high volume CVVH and hopefully the IVOIRE study will confirm /refute this. For non sepsis related AKI it may well be that we have a higher target but are we causing harm by doing this.

  2. danharvey on

    Thanks for your comment & support of the new site Alex. approx 50% of the patient group had sepsis listed either as primary cause or as part of multi-factorial process – other top causes were ischeamia (80%) or nephrotoxins (30%). Perhaps instead of targeting a given flow rate we should aim for dialysis adequacy (as in HD for CRF)?

  3. danharvey on


    well done excellent idea.

    The site is okay but i hope this reaches the webpage this time as last time it did not appear. (I wrote whie on hols-thats dedication)

    The renal paper has a number of flaws and should not be taken too literally. They filtered people at GFR of around 60mls/min which in this contry wouldnt even get you near a renal bed. Also the ppt drop in BP is a known associated factor with poor renal outcome and long term RRT so to allow this to happen in your intensive group is in fact allowing substandard care and probably accounts for the fact no benefit was found. Also they chopped and changed around patients between the groups so comparisons are difficult. Basically await the AUZ/NZ trial which has just completed.


    NB cheers Andy. Andy submitted this as a post – and I’ve changed it to a comment. If you’d like to discuss a paper, click to “comment”, if you’d like to submit a new paper click “post”. Cheers Ed (dan)

  4. sjones5 on

    An interesting paper. There is still much uncertainty about the timing and dosing of RRT in AKI – Mehta has just sent out a questionnaire to intensivists and nephrologists to try and ascertain worldwide practice. Obviously in ICU we practice something similar to the intensive arm whereas on a renal unit we usually do a more less intensive strategy – we review the renal chemistry and urine output on a daily basis (obviously looking for signs of renal recovery) and in practice dialyse most people on alternate days – it is rare that we dialyse people daily for AKI, but then again our patients usually have only single organ dysfunction, unlike the patients in this study who had failure of 1 or more non-renal systems. I cannot see where they have stated clearly at which point in terms of renal chemistry or other critieria they chose to initiate RRT (is it in the appendix?) – Dr Sharman states it was when the GFR was approximately 60mls/minute which if it is indeed the case would probably mean they didn’t need any RRT at all! All I can find is the level of BUN at initiation of RRT. Am I missing something? I can only find where they state that they chose to continue RRT if the creatinine clearance was <12mls/min.

    In reply to your comment Dan, I don’t think isolated UF should be of particular concern. We often UF patients (albeit usually our fluid-overloaded patients with ESRF on chronic HD)inbetween HD sessions if necessary, and I can’t see why it should be any different for those with AKI.

    Given that RRT is expensive, requires intensive nursing input and is not without complications it is interesting to see that no survival benefit was demonstrated in the intensive therapy group, and that it did not improve recovery in renal function.

  5. danharvey on

    This study has now been discussed at QMC’s journal club. A presentation (by Dr. Joy Abbott) of the paper can be found in the blue box, and the summary points from the discussion were….

    1. Initiation of treatment unspecified
    2. Still predominantly USA based study
    3. Suggests intensive treatment in sepsis is
    unlikely to be beneficial
    4. Should audit to ensure we are achieving the less intensive regime of 20mls/kg/hr
    5. Potential cost saving of moving to a less intensive regime (? Increase filter longevity)

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