Understanding Concepts in Dialysate Flow
By Dr. John Agar
A recent thread of posts at the Home Dialysis Central FaceBook site contained a couple of erroneous comments that suggested some underlying misconceptions I couldn't resist addressing.
One appeared to imply that current dialysis was either “single pass” or “multi-pass”... as if there were a choice, or two options available. The other misinterpreted the efficiencies (or otherwise) of flow rates - in particular, dialysate flow rate, but also of blood flow rate.
First, single pass vs. multi-pass: what exactly do these terms mean?
Though there has been some nice work from James Heaf from Denmark on the opportunities that a multi-pass system might bring (see a short summary), multi-pass haemodialysis is a much different concept than the conventional single pass dialysis systems we use in dialysis today.
All current commercially available counter-current dialysate flow systems, including NxStage, are single pass systems. Countercurrent means that the blood flows in the dialyser in the opposite direction as the dialysis fluid.
The differences between commercial systems are to do with flow rate—blood flow rate and dialysate flow rate—not the number of times the dialysate travels past the blood compartment.
Sorbent dialysate regeneration systems have generally served as the classic model for a multi-pass dialysis system, but there are no commercially available sorbent systems at the moment. In the past, there have been the REDY system, which effectively disappeared in the early 1990's, and, briefly between 2006 and 2007, the RenalSolution Inc. Allient Eagle. Both are now extinct. So, while James Heaf's wonderful work is a most intriguing and sensible application of the multi-pass concept, and more may yet come of it, let me now leave the concept of multi-pass behind, and think JUST of dialysate flow.
Second, dialysate flow and phosphate removal.
A comment suggested that a lower dialysate flow rate in a Fresenius Baby K system will remove more phosphate than a faster flow, given the same treatment time. This statement compared phosphate removal between two options of a single variable during a 6-8 hour x 4-5 times/wk dialysis regime, one a lower (300 ml/min) dialysate flow rate vs. a faster (500 ml/min) dialysate flow rate. It suggested that phosphate removal would be greater at the lower dialysate flow rate.
Indeed, phosphate removal will be a little higher—not lower—with the faster rate than the slower flow rate, though there would not likely be a huge lot in it. No...it is treatment time that plays the greater role in phosphate removal, not dialysate speed.
In our own nocturnal service, we set a flow rate of 300 ml/min for our many dozens of long, slow (8-9 hr), frequent (4-5 nights/wk) nocturnal patients, but this is more to conserve water than to influence clearance, as the clearance benefit is primarily derived from time, not dialysate flow rate. We still remove so much phosphate that we usually need to give some back by adding phosphate to the dialysate!
Thinking, for a moment, about single pass conventional dialysis systems, the total dialysate volume needed for each treatment is clearly determined by flow rate and treatment time: - A dialysate flow rate of 300 ml/min will require (ie: use up) 300 ml x 60 min/hour = 24 litres/hour. - At a flow rate of 500 ml/min, the dialysate requirement would be 500 x 60 = 30 litre/hour.
Thus, in the setting of a “standard” 4 hour treatment, a total dialysate volume of 96 (@300) or 120 litres (@500) would be needed. Blow these out to an 8 hour nocturnal treatment and 192 (@300) or 240 litres (@500) would be needed. While that is ok, the higher the dialysate flow rate, the more water-greedy the system. It then boils down to a trade-off decision between the clinical clearance benefit of a higher flow rate (if any) and the practical availability and cost of water.
Whichever way the bread is buttered, conventional dialysis is water greedy, and does require so much water, that travel-friendly dialysate volumes are not possible, at least not without a travel-friendly reverse osmosis system...and, as yet, there isn't one!
To facilitate a travel mode and minimise the required dialysate volume to a manageable 30 litres (ie: 6 bags holding 5 litres each ) = about the maximum bagged dialysate volume that can be 'reasonably transported' for a single treatment, NxStage HAD to come up with a novel and REALLY slow dialysate flow concept. This had to be one that would permit a low enough total per treatment dialysate volume to make portability feasible, yet still “clear” (i.e., remove) sufficient “stuff” to provide adequate dialysis. Clearly, 96 - 240 litre volumes—as above—were NOT consistent with a transportable system.
So, they chose to lower the dialysate flow way down to 30 litres/treatment. For example, if dialysate flow rate could be lowered to 150 ml/minute (= 9 litres/hour) for a total treatment time of 3 hours, only 27 litres of dialysate would be needed per treatment.
But...and this can be the hard bit to get your head around…as a slower dialysate flow rate begins to “saturate” the dialysate with waste, and thus the concentration gradient between blood and dialysate begins to lessen, waste removal begins to slow down. As the amount of waste in the dialysate relative to the amount in blood increases, less and less removal results. If the differential concentration gradient between blood (removing from) and dialysate (removing to) is reduced, the efficiency of waste removal is reduced.
Peter is beginning to pay Paul!
Recognising this clearance problem as the Achilles heel in their march to reduce the dialysate volume to a manageable, transportable, travelable volume, NxStage came up with a nifty plan to combat this efficiency problem. At least in part, they compensated by pushing up their recommended blood flow rate. They “reversed” the usual ratio of blood flow (250 ml/min) to dialysate flow (500 ml/min)—> a ratio of 1:2 to a blood flow of (say) 450 vs. a dialysate flow of 150 —> a ratio of 3:1, or similar.
They called this “new ratio” the “flow fraction.”
This flow fraction concept largely—though not fully—corrected and compensated for the lesser waste removal achieved by slowing down the dialysate flow rate. NxStage had worked out a way whereby they could reduce the required total per-treatment dialysate volume, maintain adequate clearance, and facilitate a portable system, all at the “small expense” of needing a very fast blood flow rate.
But, nothing is ever free. High flow rates can potentially have significant implications for the vascular integrity of the fistula. I have dealt with this issue before, in a blog about fistula flow rates in 2014 at KidneyViews.
To recap, NxStage now had a model that achieved adequate (and I use that word intentionally) clearances—not “great” nor “optimum,” but “adequate”—and that achieved portability - a major goal. This came at a price, as everything does, and that price was: (1) The risk to fistula or central vein integrity, (2) The ability to achieve optimum clearance; this latter “risk” becoming especially problematic when considering the removal of time-dependent substances…like phosphate!
NxStage was designed for short, sharp, frequent runs (initially 2-2.5 hrs) to allow its low flow rate dialysate to eek adequate clearance from a limited total dialysate volume. But, while this seemed to satisfy and broaden the options for an already poorly-dialysed American dialysis population, it didn't appeal elsewhere where better dialysis was already the accepted norm. This has led to further iterations of the NxStage system, as their designers ever strive to increase the available dialysate volume back towards volumes that again preclude travel—the untransportable Pureflow—leaving the lower volume System One bag system as a lesser efficiency travel mode.
So, in summary, back to the original two statements:
- All current hemodialysis systems are single pass, including NxStage. It is just the speed of pass that is different (i.e. the ratio between the blood flow rate and the dialysate flow rate). Multi-pass is limited either to (1) a sorbent system, though no current commercial sorbent systems are out there, despite that many are being R&D'ed, or (2) a research tool - like James Heaf's nifty multi-pass version of a conventional single pass system - though this is not (yet) an option for routine management.
- The notion that using a slower dialysate flow rate in a Baby K will enhance phosphate removal is also a “no.” If anything, it is the opposite, though the length of time on dialysis is what influences phosphate clearance most, and not the dialysate flow rate.
Finally, this blog does not mean to be denigrate the NxStage system—not at all—but as with all current systems, it does have disadvantages and inefficiencies, and these should be understood. NxStage offers advantages of size and travel-ability; indeed, its original raison d'être…but all life is a series of compromises, and, just as with life, the NxStage system requires some compromises to achieve its central goal of portability and to answer the question: “How can the need for untransportably large volumes of dialysate be overcome?"
The NxStage compromises have been, for many, acceptable. But, while acknowledging the benefits that the NxStage delivers to many, there are some (and I am firmly in this camp) who, retain a preference for efficiency and clearance superiority, and will seek that goal through frequency, duration, and the use of conventional blood:dialysate ratios, until a better offers comes along.