Optimized convective volumes in postdilution HDF using ULTRACONTROL - Effect on blood purification efficacy

Hemodiafiltration (HDF) is a dialysis mode that effectively combines diffusive
and convective transport and thus, in comparison with HD, offers conditions for
enhanced removal of a wide range of uremic solutes. The greatest effect is on
the removal of large solutes, often referred to as middle molecules. The AK
200 ULTRA S on-line system by Gambro has been widely used for such HDF
treatments since 2001.
The most effective blood purification in HDF, i.e. the greatest clearance, is
achieved in postdilution mode [Ledebo, 1999]. Here ultrafiltration is applied
on undiluted blood and the substitution fluid is infused after the filter.
Theory predicts that the greater the exchange of fluid the higher the clearance
[Waniewski 1991, Sternby 2005]. Clinical experience confirms that a greater
volume in HDF is associated with greater removal of small solutes like urea and
phosphate as well as of middle-sized solutes like b2m [Lornoy 2000, Lin 2001].
Additionally, a lower mortality risk has been observed in patients regularly
treated with HDF with high exchange volumes [Canaud, 2006].
Conventionally, a postdilution HDF treatment is run in volume control, meaning
that a target infusion volume (VINF) is set at treatment start. However,
trans-membrane pressure (TMP) problems often arise during the course of HDF
treatments in volume control mode, as levels of blood cells and proteins
increase and make the filtration of plasma water more difficult. As a result,
infusion volumes are typically set in the low range of what is expected as
achievable to avoid such TMP alarms towards treatment end.
An alternative way to control HDF treatments when using the AK 200 ULTRA S
system is to set a certain TMP to be kept throughout the treatment. This mode,
using manual setting of the TMP value and referred to as Pressure Control Mode,
allows for greater infusion volumes to be reached than in conventional HDF with
volume control [Frouget, 2005].
Recently a new ULTRACONTROL feature has been developed and incorporated in the
software 8.11 version for the AK 200 ULTRA S dialysis monitor. The ULTRACONTROL
feature automatically finds the optimal TMP value to use in controlling the
infusion rate during the HDF treatment. The ULTRACONTROL mode is therefore
expected to make postdilution HDF treatments easier to prescribe and run, and
to deliver infusion volumes at level or better with the best achieved using the
current pressure control mode with manual TMP setting. Initial evaluations of
software 8.11 in dialysis clinics in Sweden, Germany, and France have confirmed
its effectiveness and ease of use.

The study objectives are
1. to compare blood purification efficacy for postdilution HDF treatment in
ULTRACONTROL mode to that of i) postdilution HDF using volume control mode, and
ii) high-flux HD treatment, using in all treatments the same dialyzer, the same
blood flow rate, and the same total dialysis fluid flow rate.
2. to evaluate in ULTRACONTROL HDF treatments the achieved convective volume
(=infusion volume + UFV) and its intra- and inter-individual variation.

Patients will be given one treatment of each of the following treatment modes,
in randomized order, during which blood purification efficacy will be
extensively evaluated from blood and dialysate samples (only mid-week; week
2-4):
• Postdilution HDF using ULTRACONTROL
• Postdilution HDF using conventional Volume Control mode
• High-flux HD
In addition (week 1; all treatments and week 2-4; treatments 1 and 3 only) nine
postdilution HDF treatments using ULTRACONTROL will be evaluated on the
delivered convective volume in relation to other treatment parameters. No blood
or dialysate samples will be collected for these treatments.
Blood flow rates and dialysis flow rates will be kept constant during the 4
study weeks.
Fluid removal according to each patient*s current needs

The intervention in this study consists out of the randomisation of the three
dialysis modalities (A) post-dilution HDF with ULTRACONTROL; (B) post-dilution
HDF with volume control and (C) standard high-flux hemodialysis. This
randomisation will only be carried out for the second treatment of week 2 to
week 4. For all other treatments (all treatments of week 1 and treatment 1 and
3 of week 2 to 4) only routine postdilution HDF with ULTRACONTROL treatments
will be done assessing the convective volume. Blood and spent dialysate samples
will only be taken during the random treatments A, B and C.

There is no extra burden to patients related to the study apart from:
• Being informed about the study and signing informed consent
• Blood loss of maximum 60 ml blood in 3 weeks time

This study fits well in current routine dialysis treatment of our current
patients. No additional risks are foreseen. Some patients for which HDF is
prescribed may feel less comfort during 1 out of 12 treatments when randomised
to standard high-flux HD but since this treatment is mid-week this risk is low.