Cold dialysate for cardiac protection

This month’s CJASNeJC is a randomized controlled trial of cold dialysate and its effect on the heart.

The introduction begins by stating that hemodialysis itself causes recurrent ischemic damage to the heart, brain, and other organs. This leads, in the case of the heart, to long-term contractile dysfunction, abnormal ventricular morphology, and increased mortality. Based off a number of pilot studies, the authors hypothesis is that use of cold dialysate will ameliorate these cardiac complications.

This is a multi-center, randomized controlled, open-label, but blinded end-point, study.


Inclusion criteria:

  • Age 16 or over
  • Three-days a week dialysis
  • Initiated dialysis in the last 180 days
  • Capacity to consent

Exclusion criteria

  • Inability to tolerate cardiac MRI
  • NYHA heart failure grade 4


  • Dialysis staff and patients were not blinded to the temperature of the dialysate
  • Cardiac MRI, the primary outcome was done centrally and was performed and evaluated by investigators blinded to the patients’ study group


  • The control group was dialyzed with dialysate at 37°C for 12 months
  • The intervention group was dialyzed with dialysate lowered 0.5°C below body temperature with a maximum of 36° and a minimum of 35°C.


Primary outcome

  • Change in ejection fraction at 12 months as determined by cardiac MR

Secondary outcomes

  • LV Mass
  • LV Volume
  • Peak systolic strain
  • Peak diastolic strain
  • Aortic distensibility


73 patients were randomized and 54 were included in the analysis. 11 received the intervention but did not receive a baseline cardiac MR and 8 did not receive the intervention due to withdrawal, death, pregnancy, or intercurrent illness.

Only 44 completed the trial and had the follow-up cardiac MR. ( 1 death, 5 kidney transplants, 3 declined follow-up cardiac MR, and 1 pacemaker insertion) A prospective power analysis determined a need for 52 patients, so this study missed its power analysis.

The achieved dialysate temperature was not reported for the control group but was 35.8 °C in the experimental group.


Primary outcome

  • There was no change in the primary outcome, the ejection fraction, between the two groups.

Secondary outcomes

  • There was a signifigant reduction in LV mass in the intervention group (decreased by 15.6 g compared to control).
  • There was a signifigant reduction in LV-end diastolic volume in the intervention group (-23.8 mL).
  • Global LV systolic function was maintained in the experiemntal group but fell in the control group.
  • Peak systolic strain rate was preserved in the experimental group and fell in the control group.
  • There was also preservation of diastolic function in the experimental group relative to the control group.
  • Segmental strain reduction was found in 10 of 16 LV segments in the control group compared with no reduction in the experimental group.
  • Aortic distensibility was preserved in the experimental group and decreased in the control group.


The authors emphasize that though their primary outcome was not affected by the intervention a broad array of secondary outcomes were impacted:

The more recent application of strain analysis has confirmed the prognostic value when the EF is preserved, supporting that the EF may not have been the optimal primary cardiac imaging–based outcome. In this trial there was a clear and consistent signal of both preservation of function directly measured by LV strain and inferred from reductions in LV mass and LV dilation that the cooling intervention was effective at protecting the heart.

Then the authors outline that the cardiac changes they saw were similar to the results of the Frequent Hemodialysis Network which also demonstrated reductions in LV mass and LV end-diastolic volume without a change in ejection fraction.

The authors then outline the scope of the trial needed to assess whether cold dialysate would reduce cardiac complications. What would it take to move beyond the surrogate endpoints. They estimate a using 14 centers with 121 patients each (N=1,700) and followed for 3 years would be required to demonstrate a 20% reduction in a composite end-point of all-cause mortality, and hospitlaization with major CV event. This is on the scale of the HEMO trial (1,846 patients with average follow-up of 2.9 years). The authors then back away from such an ambitious study by suggesting we adopt the results based on current data:

However, because dialysate cooling is universally applicable without cost and well tolerated, with no apparent harm and probable benefits to both the heart and brain, dialysis clinicians and patients may alternatively consider that these data approach proof beyond a reasonable doubt and adopt wider use without further trials.


An editorial by Maria Eleni Roumelioti and Mark L. Unruh points out that this was a small study of surrogate outcomes. Additionally selecting only incident patients somewhat limits the applicability of the results.

They also point out that the experimental group had a larger baseline LV mass and that this may responsible for the difference between the groups seen at the end of the study.

The editorial then describes a study by Selby, et al. that examined 10 patients with a history of intra-dialytic hypotension. They did echocardiograms during dialysis at 37 °C and 35 °C to look for regional wall motion abnormalities (RWMA). They found that dialysis at 35 °C improved EF, and decreased RWMA. The conclusion was that cool dialysate reduced subclinical ischemia.

Selby NM, et al. CJASN 1: 1216–1225, 2006

The editorial concludes with the authors calling for a large-scale study of dialysate temperature.

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