NxStage dialysate flow rates

By Peter Laird, MD

In response to Zach's comments (here and here) on the resurgence of home dialysis and NxStage dialysate flow rates, if you look at the NxStage theoretical 100% dialysate clearance when flow rates are at 100ml/min and then follow the curve up and to the right, you should be able to get better clearance by increasing dialysate flow rate up to 200 ml/min and still be near the theoretical 100% clearance that the NxStage system is based upon. To better illustrate this, go to the following link from a Well Bound PPT lecture (pdf link), (may load slow) to the 19th slide titled: HD therapy dosing with NxStage.

slide from Wellbound pdf

This graph demonstrates the theory behind the NxStage low dialysate flow to take advantage of the "100%' efficiency at that part of the curve. Looking to the right of the 100 ml/min flow, we see that the curves do not diverge until nearly at the 200 ml/min. So, in answer to Zach's first question, I do believe that there is a potential to increase the efficiencies of total clearance on NxStage with a higher dialysate flow rate up to the 200 ml/min level. (I am still looking for a nephrologist that will prescribe the maximum dose/patient instead of the stale “adequate” dose derived by urea clearances.)

Just a quick editorial note. It appears to be common practice to check the urea clearance on NxStage and then adjust the time and amount of dialysate to that number. Most of the time this is to reduce the time and dialysate dosage to the level of an adequate clearance goal. I find this to be a continuation of the fallacy of dialysis adequacy that we continue to warn about with usual in center care. Old American habits die hard. If we have learned anything from our overseas colleagues, the two most important factors in dialysis survival is the combined dialysis dosage of frequency and duration. Lowering dialysis dosage based on an arbitrary number with dubious clinical validity is to ignore what have learned about middle molecule clearance that is modifiable mainly by increased frequency, duration or best of all maximum frequency and duration with nocturnal regimens.

Now as for the second part of Zach's question on high flux vs. low flux artificial kidneys. In the HEMO study, this was answered quite well that the expected improvement with high flux dialysis was not found: (the total per session length in the HEMO study was not long enough to find the survival advantage that nocturnal studies have found.)

In summary, although the effect of the dose and level of membrane flux may vary among selected subgroups of patients, the primary results of our study indicate that, with a schedule of thrice-weekly dialysis, neither an increased dose of dialysis nor use of a high-flux membrane substantially improves survival, reduces the rate of hospitalization, or maintains serum albumin levels as compared with a standard dose and use of low-flux membranes.

Thus, those that prescribe NxStage dialysis therapies for their patients will need to acknowledge that not only is increased frequency important as they are beginning to realize, but also that total duration/week is likely the most important survival factor. I am frankly surprised that NxStage has only achieved a 10% annual mortality for the patients using their machines especially given the much younger age of the NxStage population. Perhaps the lower clearances of low volume dialysate combined with only 12-15 hours/week average dialysis duration with the usual short daily NxStage regimen is simple not enough of a good thing. Experimenting with dialysate flow rates up to 200 ml/min is justified in my mind simply by observing the dialysate flow curves above.

Yet, we are still fighting the battle even with NxStage home dialysis of increased dialysis total dosage. Why stick to only half of the dialysis dosage equation: dosage = frequency X duration. The data from Australia is clear (pdf link), total time/week on dialysis is perhaps the single most important factor in survival. Increased frequency is definitely an important factor as far as quality of life improvements, but total duration of over 20 hours/week is independent of frequency for improving survival to the 2% annual mortality rate. Frequency alone at a low daily duration does not get us to that survival level.

I am encouraged by the NxStage option which I am still on the wait list for through my insurer, not through my FMC unit. I do have the option of the K machine through my FMC unit, but that would leave me dependent on usual care at dialysis units that do not have the professionalism of my home unit whenever I would visit my family out of state. After several weeks of feeling terrible last summer in out of state units, having control of my dialysis sessions with my own portable machine wherever I am is my highest priority at this time.

Thus, aside from some potential short falls with the NxStage system that must be taken into account, I do believe that if I can convince my nephrologist that duration and frequency are much more important than hypothetical urea clearances and get over 20 hours/week of dialysis on NxStage, then I can gain the survival advantage that I am seeking with the home dialysis treatment option.

Comments

[Pat Colongione]

Dr. Laird,
My husband Ralph is on Nxstage and we do nocturnal 6 nights a week. He is dialysed for 8.5 hrs per night. We use a BFR of 340 and a FF of 35. His last month's spKt/V was .99, eKt/V is .92 and his std Kt/V is 4.03.
His pre BUN was 32 and post was 14.
Needless to say he is doing really well. He gets 51 hrs of dialysis a week. Not quite like kidneys but pretty close.
You keep fighting. Because more is definately better.
Pat

[Zach]

Instead Kt/V urea, I'd like to see a middle molecule solute used as a marker, such as β2-microglobulin.

That's what I meant by type of dialyzer used when dealing with optimal hemodialysis.

[Peter Laird, MD]

Zach, I agree completely that a middle solute molecule marker would be the best measure of dialysis efficiency. Unfortunately, several have been proposed but due to various factors, none have been accepted yet.

As far as the B2 microglobulin, one confounding factor is that ultrapure dialysate with much lower levels of endotoxin (endotoxin comes from bacterial cell walls and is known to cause inflamation when we are exposed to it) has been shown to reduce B2 microglobulin levels significantly. That leads me to question whether it is correct that we don't need sterile dialysate. Perhaps we don't become infected after a dialysis session from unsterile dialysate, but who can question the adverse effects of endotoxin derived inflammation on chronic dialysis patients.

Thus, one of the problems of using B2 microglobulin is that unsterile dialysate increases this marker independently of its clearance. Other problems are in the diffusion rates of this molecule out of interstitial tissues thus doubly confounding it as an accurate marker of dialysis clearance rates.

Unfortunately, small molecule clearance with the urea kinetics dominates this discussion and it is not likely that American nephrologists will give this up any time soon.

Lastly, the experience with low Qb rates seen oversees shows clearly that the results found in the HEMO study with high flux vs. low flux is not the answer with increased clearance rates per session. Europe has much lower Qb rates than America with longer sessions. I believe that reflects the issue of middle molecule diffusion which simply takes longer to accomplish than the small urea molecule.

In summary, this is a long answer to simply agree with you that middle molecule clearance measurements will better reflect dialysis optimalization. Unfortunately, old habits in the medical field die hard. Just ask the ghost of Ignaz Semmelweis how many doctors wash their hands inbetween their patients even today.

http://en.wikipedia.org/wiki/Ignaz_Semmelweis

If doctors will not even submit to a few seconds of hand washing in between their patients, which many do not, then how much more effort will it take to make the frame shift change from small molecule kinetics to middle molecule kinetics? Perhaps we will need to ask that question of the ghost of Belding Scribner.

[Peter Laird, MD]

Zach, if you havn't already taken a look at Dr. Agar's discussion on this issue, it certainly is a great place to start.

http://www.nocturnaldialysis.org/opthd1.htm

[John Agar]

Dear Peter

All I can say is ... at least there are a few enlightened souls over there. You are utterly correct in what you say. When will people that dialysis is NOT governed by urea clearance (oh, what a sad day the advent of Kt/V was for all of us) and that it is NOT just frequency but time, total time, that matters. All I can say is that I, as a voice form the wilderness, agree with you. I am glad someone there (you) is continuing to point to the data Carmel Hawley presented for us to the Australian and New Zealand Society of Nephrology in August last year and which underpins our belief, here, in longer and more frequent dialysis (it can be found at http://www.anzdata.org.au/ANZSN/2008/HomeHDreport.pdf ). Most of the correspondence I read still makes me weep with frustration at the blinkered urea-centric view of dialysis that makes up the mass of US thought.

[Brian Steele- Sierk]

I second the experience of the first poster. Nocturnal (I do 7x week) gets the total weekly hours up around 45-55, and the overall quality of life dramatically improves.

The 10% is not where it needs to be, but it beats the crap out of the in center mortality rate.

The change is going to come from patients fighting for it. Most doctors are responding to the "I want to be on dialysis as little as possible" mind set- i.e. time on dialysis is time spent away from life, so short dialysis improves overall quality of life. Most doctors will respond to a patient demanding access to extended , nocturnal care.

There also needs to be government re-evaluation of costs. For instance, my insurance company is saving a bundle by paying for home nocturnal as I have been able to go off both binders and blood pressure medication. even reduction in binder usage will create marginal savings that create budgetary space for investment in infrastructure and training.

Centers, however, are dis-incentivised to do more dialysis under the current compensation plans.

[Peter Laird, MD]

Dear Brian, thank you for your comments. It is a wonderful thing that you are able to obtain optimal dialysis for your situation. I am not quite so sure that I will be able to do the same any time soon even with NxStage since all that is offered and promoted is short daily dialysis with 15-20 L of dialysate per session. I have the task before me of educating my nephrologist on duration as well as frequency issues.

In addition, Japan and Europe achieve much better mortality rates in their in center units from average duration over 4 hours each session unlike many American units that average 2.5 - 3 hours per session. In fact, my own FMC unit had a 7% mortality rate in 2008 attributable to several factors, but in my mind, the commitment of our nephrologist to a standard 4 hour duration is a large part of it.

So, yes, 10% is a vast improvement over the usual 24% killing rates of most units, but even with usual three times/week dialysis, less than 10% mortality is easily achievable. That leads me to question why NxStage with much younger patients on average has only risen to a 10% level. I believe that a big part of this picture is that most NxStage users only on short daily dialysis. As Dr. Agar so eloquently states, duration of dialysis is one of the most important factors in survival.

So my hat is off to NxStage for educating people on the frequency of dialysis issues, it is time for them and others to acknowledge the second half of the survival equation.